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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Atrial fibrillation &#40;AF&#41; is the most common sustained cardiac rhythm disorder and constitutes an important risk factor for stroke&#44;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> associated with a five-fold risk<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>&#58; 15&#37; of all strokes are attributable to AF and around 25&#37; of patients with ischemic stroke present AF&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The prevalence of AF in the general population in developed countries is approximately 1&#46;5&#8211;2&#37;&#46; In addition&#44; the mean age of patients with this condition is steadily rising&#44; such that it now averages between 75 and 85 years&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> According to the FAMA &#40;Atrial Fibrillation in Portugal&#41; study&#44; the prevalence of AF in the Portuguese population aged 40 and over is 2&#46;5&#37; &#40;95&#37; confidence interval &#91;CI&#93;&#58; 2&#46;2&#8211;2&#46;8&#37;&#41; and increases with age&#44; reaching 6&#46;6&#37; for individuals aged 70&#8211;79&#44; and 10&#46;4&#37; for those aged 80 or more&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Guidelines for stroke prevention in AF have been developed to encourage best practice and a systematic approach to treatment by physicians&#44; with the intention of achieving the best outcome for the AF patient&#46; The clinical guidelines on antithrombotic therapy for AF issued by the Portuguese National Coordinating Body for Cardiovascular Disease&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> the European Society of Cardiology &#40;ESC&#41;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and the American Heart Association&#47;American Stroke Association &#40;AHA&#47;ASA&#41;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> are generally accepted by the Portuguese medical community&#46; Overall&#44; these guidelines consider oral anticoagulants &#40;OACs&#41; the cornerstone of thromboembolic prevention in AF&#46; Vitamin K antagonists &#40;VKAs&#41;&#44; primarily warfarin&#44; are widely regarded as the current standard of care&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">A meta-analysis of trials on antithrombotic therapy in the prevention of stroke in non-valvular AF shows that VKAs significantly reduce the risk of stroke by 64&#37; vs&#46; placebo&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Although effective&#44; VKAs have limitations that make patient management challenging in practice&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> For instance&#44; the anticoagulation response to VKA treatment is unpredictable and is affected by genetic and environmental factors such as drug-drug and food-drug interactions&#46; The high inter- and intra-patient variability in response to therapy means that frequent blood tests for international normalized ratio &#40;INR&#41; monitoring &#40;an INR 2&#46;0&#8211;3&#46;0 is recommended&#41; and dose adjustments are necessary&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The 2012 ESC guidelines state that new OACs such as rivaroxaban are generally preferable to VKAs in patients with non-valvular AF&#44; when used as studied in the clinical trials performed to date&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Over the past decade&#44; risk factor scoring systems have been widely used to stratify the risk of thromboembolism in non-valvular AF&#46; The simplest risk assessment scheme is the CHADS<span class="elsevierStyleInf">2</span> score &#40;congestive heart failure&#44; hypertension&#44; age &#8805;75&#44; diabetes&#44; stroke &#91;doubled&#93;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc score &#40;congestive heart failure or left ventricular dysfunction&#44; hypertension&#44; age &#8805;75 &#91;doubled&#93;&#44; diabetes&#44; stroke &#91;doubled&#93;&#44; vascular disease&#44; age 65&#8211;74&#44; and sex category &#91;female&#93;&#41;&#44; which considers additional risk factors&#44; more accurately identifies patients at very low risk for stroke and is recommended in the ESC 2012 guidelines&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Rivaroxaban &#40;Xarelto<span class="elsevierStyleSup">&#174;</span>&#41; is a new OAC&#59; it is a highly selective&#44; oral&#44; once daily&#44; direct factor Xa inhibitor&#46; Rivaroxaban has predictable pharmacokinetics and pharmacodynamics&#44; few relevant drug interactions&#44; and does not require monitoring of coagulation parameters&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The efficacy and tolerability of rivaroxaban for prevention of stroke and systemic embolism &#40;SE&#41; in AF patients has been compared with warfarin in the ROCKET AF &#40;Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation&#41; trial&#46; ROCKET AF is a multinational&#44; phase III&#44; randomized&#44; double-blind&#44; multicenter&#44; event-driven study&#44; involving 14 264 patients in whom treatment with OACs was recommended&#46; In the primary analysis&#44; rivaroxaban demonstrated a 21&#37; risk reduction in event rate for stroke and SE &#40;hazard ratio &#91;HR&#93; 0&#46;79&#44; 95&#37; CI 0&#46;66&#8211;0&#46;96&#44; p&#60;0&#46;001 for non-inferiority in the per-protocol&#44; as-treated population and HR 0&#46;79&#59; 95&#37; CI 0&#46;65&#8211;0&#46;95&#44; p&#61;0&#46;02 for superiority in the safety&#44; as-treated population&#41; compared with warfarin&#46; Additionally&#44; rates of intracranial &#40;IC&#41; bleeding&#44; fatal bleeding and bleeding at critical anatomical sites were significantly lower in the rivaroxaban treatment arm compared to the warfarin treatment arm &#40;HR&#58; 0&#46;67&#44; 95&#37; CI &#91;0&#46;47&#8211;0&#46;93&#93;&#44; p&#60;0&#46;02 for IC bleeding&#59; 0&#46;50 &#91;0&#46;31&#8211;0&#46;79&#93;&#44; p&#61;0&#46;003 for fatal bleeding and 0&#46;69 &#91;0&#46;53&#8211;0&#46;91&#93;&#44; p&#61;0&#46;007 for bleeding at critical anatomical sites&#41;&#46; <a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The Portuguese pharmaceutical market has been affected by a series of policy measures over the last decade&#44; including the introduction of a reference pricing system&#44; administrative price reductions&#44; and various changes in co-payment regulations&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In the context of an economic crisis&#44; health economic evaluations such as cost-effectiveness analyses &#40;CEAs&#41; can be useful tools to inform resource allocation decisions in a systematic&#44; transparent and efficient manner&#46; The main outcome of a CEA is an estimate of the costs and effects associated with the new technology compared with alternative treatment&#40;s&#41; such as standard of care&#44; in order to indicate whether the new treatment provides good value for money to the health care payer&#46; Hence&#44; the main aim of this study was to undertake a CEA comparing rivaroxaban with warfarin for stroke prevention in patients with non-valvular AF&#46; An additional analysis in which rivaroxaban was compared with real-world prescribing &#40;no treatment&#44; aspirin and warfarin&#41; was performed&#44; since the existing evidence indicates underuse and underprescription of warfarin in Portugal&#46; This model supported the reimbursement request for rivaroxaban in Portugal in this therapeutic indication&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Model overview</span><p id="par0040" class="elsevierStylePara elsevierViewall">An analysis was performed to project the long-term cost-effectiveness of treating AF patients with rivaroxaban compared to warfarin for the prevention of stroke in the Portuguese setting&#46; The analysis was conducted using a previously described economic model&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The Markov model used included health and treatment states describing the management and consequences of AF&#46; The outcomes of the model included incremental life-years &#40;LYs&#41;&#44; incremental quality-adjusted life years &#40;QALYs&#41;&#44; incremental costs&#44; and incremental cost-effectiveness ratios &#40;ICERs&#41; expressed in terms of &#8364;&#47;LY gained and &#8364;&#47;QALY gained&#46; The base-case analysis was conducted from a societal perspective using direct costs only&#46; The model&#39;s time horizon was set at a patient&#39;s lifetime in order to fully incorporate the costs and consequences of AF&#46; The mean age of patients in the model was set to 73 years and the lifetime horizon was therefore set to 20 years&#46; Costs and outcomes were discounted at a 5&#37; annual rate&#44; in accordance with the most recent recommendations for economic evaluations published in Portugal&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Patient population</span><p id="par0050" class="elsevierStylePara elsevierViewall">The patient population that was considered in the base-case analysis matched that of the ROCKET AF clinical trial&#58; patients suffering from non-valvular AF with a CHADS<span class="elsevierStyleInf">2</span> score &#8805;2 &#40;mean CHADS<span class="elsevierStyleInf">2</span> score 3&#46;5&#41;&#44; of whom 62&#46;5&#37; had previously been treated with VKAs&#46; Based on the opinion of an expert panel&#44; management of VKA treatment was assumed to be undertaken primarily in a specialist setting &#40;65&#37; of patients&#41;&#44; with the remaining patients &#40;35&#37;&#41; managed in a primary care setting&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Model structure</span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Model health states</span><p id="par0055" class="elsevierStylePara elsevierViewall">The model was designed to reflect the progression of AF patients through different health states up to death&#46; A cycle length of three months was deemed short enough to adequately capture the frequency of major events&#46; Patients entered the model with stable uncomplicated AF and received treatment with either rivaroxaban &#40;20 mg oral tablet&#44; once daily&#41; or dose-adjusted warfarin &#40;target INR of 2&#46;0&#8211;3&#46;0&#41;&#46; Patients who discontinued treatment were assumed to receive aspirin irrespective of initial treatment&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In the model&#44; patients were assumed to be always at risk of major complications unless they were currently experiencing an acute event in the same cycle&#46; Major complications considered in this model included ischemic stroke&#44; either minor or major&#44; SE&#44; myocardial infarction &#40;MI&#41; and bleeding&#46; Bleeding events were categorized as major extracranial &#40;EC&#41;&#44; major intracranial &#40;IC&#41; or clinically relevant non-major &#40;CRNM&#41; as defined in the description of the rationale and design of the ROCKET AF trial&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Major events were classified as transient or with permanent after-effects &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Boxed events were considered permanent while non-boxed events were considered transient&#46; Each health state had a cost and utility weight describing associated quality of life as a pay-off&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Model input data</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Efficacy and safety data</span><p id="par0070" class="elsevierStylePara elsevierViewall">In a Markov model&#44; patients move from one health state to another with particular probabilities referred to as transition probabilities&#59; these are primarily derived from clinical trials&#46; In the base-case analysis&#44; baseline event rates &#40;i&#46;e&#46; the probability of moving from one health state to another&#41; were obtained from the warfarin treatment arm of the ROCKET AF trial&#46; Relative treatment effects describing the efficacy and safety of rivaroxaban vs&#46; warfarin for the prevention of stroke and SE were then applied to these baseline event rates &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Persistence and discontinuation rate</span><p id="par0075" class="elsevierStylePara elsevierViewall">Persistence is a measure of whether patients continue or discontinue their current treatment&#46; Given that limited data for real-life persistence were available for rivaroxaban&#44; the model used discontinuation rates for the initial cycle of 8&#46;9&#37; and 8&#46;0&#37; for rivaroxaban and warfarin&#44; respectively&#44; from the ROCKET AF trial&#46; In subsequent cycles it was 4&#46;39&#37; and 4&#46;46&#37;&#44; respectively&#46; In the model&#44; patients who had discontinued treatment transitioned into a mirror health state&#46; Patients who discontinued were assumed to switch treatment to aspirin&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Mortality</span><p id="par0080" class="elsevierStylePara elsevierViewall">In the model&#44; mortality was accounted for in two ways&#58; by considering age-adjusted mortality rates from the Portuguese general population and by capturing event-related mortality&#46; For general population mortality rates&#44; life tables published by the Portuguese National Institute of Statistics<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> were used&#46; In addition&#44; after experiencing a major ischemic stroke&#44; major bleeding event &#40;EC or IC&#41; or MI&#44; it was assumed that patients may die with a probability equal to the case-fatality rate observed in ROCKET AF&#46; Minor ischemic stroke&#44; SE and CRNM bleeding events were assumed to have no associated case fatality&#46; Patients who had experienced a major ischemic stroke or MI were assumed to have an increased mortality rate&#44; despite recovery from the acute episode&#44; as the evidence shows extended impact on life expectancy&#46; Since post-recovery mortality data were not available from the ROCKET AF trial&#44; these mortality rates were derived from the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;20</span></a> For post-IC bleeding&#44; since no mortality rates were identified in the literature&#44; the increase in subsequent mortality rates was assumed to be equal to that following a major ischemic stroke<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Utility values</span><p id="par0085" class="elsevierStylePara elsevierViewall">The term utility refers to the preferences individuals or society may have for any particular set of health outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Utility analysis is a particularly useful technique in health economic evaluations because it allows for quality of life adjustments to a given set of treatment outcomes while simultaneously providing a generic outcome measure for comparison of costs and outcomes in different programs&#46; The generic outcome is usually expressed using QALYs&#46; A QALY is derived by adjusting the length of time affected through the health outcome by the utility value of the associated health status<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> and is calculated by multiplying life-years by utility scores&#46; Due to a lack of Portuguese-specific utility values&#44; this analysis incorporated utility values from a combination of studies in the international literature&#46; A utility value of 0&#46;779 was assigned to stable AF patients&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Utility values of 0&#46;189&#44; 0&#46;641 and 0&#46;660 were assigned for the health states of major ischemic stroke&#44; minor ischemic stroke<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> and SE<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> respectively&#44; while the values 0&#46;482 and 0&#46;719 were considered for post major ischemic stroke and post minor ischemic stroke&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Finally&#44; utility values of 0&#46;776 and 0&#46;598 were assigned for CRNM and major EC bleeding&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Data on costs and resource use</span><p id="par0090" class="elsevierStylePara elsevierViewall">Identification and quantification of resource use were estimated by an expert panel&#46; The following direct costs were considered&#58; drug acquisition&#44; drug monitoring costs and event-related costs&#46; All costs were expressed in 2011 euros&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Unit costs were obtained from published Portuguese official sources&#44; namely Orders in Council &#40;<span class="elsevierStyleItalic">Portaria</span> no&#46; 139&#47;2009<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and <span class="elsevierStyleItalic">Portaria</span> no&#46; 220&#47;2011<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>&#41; and reports issued by the Central Administration of the National Health System &#40;NHS&#41; &#40;Analytical Accounts of NHS hospitals<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>&#41;&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Drug acquisition costs were estimated on the basis of the daily dose estimated by the expert panel and costs were obtained from the Portuguese Ministry of Health&#39;s INFOMED database&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Monitoring costs related to warfarin treatment included costs of physician monitoring and INR testing&#46; Monitoring cost differed according to setting of care &#40;general physician or specialist&#41;&#46; In clinical practice&#44; when patients begin warfarin for the first time&#44; or after a period without taking it&#44; regular INR monitoring by a physician is recommended&#46; Based on the expert panel&#39;s opinion&#44; during the first three months of warfarin treatment it was assumed that patients required seven monitoring visits&#46; Thereafter&#44; patients required 3&#46;5 monitoring visits per cycle&#44; based on the findings of a Portuguese study&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Although treatment with rivaroxaban or aspirin does not require blood monitoring&#44; it was conservatively assumed that two physician visits per year were necessary based on the European Heart Rhythm Association Practical Guide<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> and the opinion of the expert panel&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Costs were assigned to acute events and to those with long-term sequelae&#46; The most severe events&#44; such as ischemic stroke and major IC bleeding&#44; were modeled using multiple components for calculating the acute costs&#46; Besides the cost of acute treatment&#44; long-term costs associated with an acute event&#44; such as its impact on functional status&#44; were also considered by including a cost for rehabilitation&#46; The latter was assumed to be incurred by the patient until the end of the first three-month cycle after a major ischemic stroke or IC bleed &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Analyses performed</span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Base-case analyses</span><p id="par0115" class="elsevierStylePara elsevierViewall">In the base-case analysis&#44; an ICER was derived by dividing the incremental costs by the incremental LYs or QALYs gained with rivaroxaban compared to warfarin&#46; Unlike several countries&#44; such as the United Kingdom&#44; the Portuguese Health Authority &#40;INFARMED&#41; does not use an explicit willingness-to-pay threshold when assessing ICERs&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Sensitivity analyses</span><p id="par0120" class="elsevierStylePara elsevierViewall">Sensitivity analyses assess the uncertainty around outputs from economic models and represent an important element of a sound economic evaluation&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> Extensive sensitivity analyses were carried out in order to further evaluate the findings of the model&#58; a one-way sensitivity analysis &#40;OWSA&#41; was carried out in order to identify the key drivers of cost-effectiveness and a probabilistic sensitivity analysis &#40;PSA&#41; was performed to test the overall robustness of the model&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In the OWSA&#44; the base-case value of parameters was varied using low and high values within plausible ranges&#46; For parameters such as clinical efficacy values&#44; the reported 95&#37; CIs from the ROCKET AF trial were used&#46; The base-case value of cost inputs were varied by &#177;25&#37;&#44; which was considered sufficient variation to capture the relevant uncertainty&#46; PSA is a stochastic analysis conducted to test second-order uncertainty in the model&#46; In this analysis 500 simulations were run&#44; each time varying all model parameters carrying second-order uncertainty within logical ranges&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Scenario analysis</span><p id="par0130" class="elsevierStylePara elsevierViewall">Given the underuse of OAC in Portugal&#44;<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6&#44;32</span></a> an additional analysis was conducted using a mixed comparator composed of no treatment &#40;6&#37;&#41;&#44; aspirin &#40;44&#37;&#41; and warfarin &#40;50&#37;&#41;&#44; which better reflects real-world prescribing in the Portuguese setting&#46; The composition of this mixed comparator was based on the literature<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33&#8211;36</span></a> and expert opinion&#46; The patient population for this additional scenario was defined by the expert panel to be the stroke risk group with a distribution among patients set to 30&#37; CHADS<span class="elsevierStyleInf">2</span> risk score of 2 and 70&#37; CHADS<span class="elsevierStyleInf">2</span> risk score of 3 or higher&#46; Among warfarin patients&#44; 25&#37; were considered warfarin-na&#239;ve&#46; Relative treatment effects describing the efficacy of rivaroxaban vs&#46; the mixed comparator for the prevention of stroke&#44; SE&#44; bleeding and MI were based on results from a network meta-analysis &#40;NMA&#41;&#46; This NMA was conducted to allow comparison of rivaroxaban with non-VKA comparators&#44; which were not included in the ROCKET AF trial&#46; Baseline event rates were set as the placebo arms of clinical trials used in the NMA&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a></p></span></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Results</span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Base-case analysis</span><p id="par0135" class="elsevierStylePara elsevierViewall">Over a patient&#39;s lifetime horizon&#44; and compared with warfarin&#44; rivaroxaban was projected to be associated with an additional cost of &#8364;81 as well as with a gain of 0&#46;023 LYs and 0&#46;021 QALYs&#44; resulting in an ICER of &#8364;3494&#47;LY and &#8364;3895&#47;QALY&#46; Assuming a &#8364;30 000&#47;QALY willingness-to-pay threshold&#44; rivaroxaban is deemed a cost-effective alternative compared to warfarin &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Sensitivity analyses</span><p id="par0140" class="elsevierStylePara elsevierViewall">The OWSA showed that the key drivers of cost-effectiveness were the clinical and economic inputs&#44; particularly discontinuation and subsequent discontinuation rate for rivaroxaban and relative risk for rivaroxaban vs&#46; warfarin for stroke&#46; Additional analyses were run assuming shorter time horizons &#40;10 and 15 years&#41; and&#44; as expected&#44; marginally higher ICERs were obtained&#58; &#8364;4286&#47;QALY for a 10-year time horizon and &#8364;3910&#47;QALY for a 15-year time horizon&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The results of the PSA confirmed the overall robustness of the base-case analysis&#46; The cost-effectiveness acceptability curve showed that at a willingness-to-pay threshold of &#8364;30 000&#47;QALY&#44; the likelihood of rivaroxaban being cost-effective compared to warfarin was 72&#37; &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Scenario analysis</span><p id="par0150" class="elsevierStylePara elsevierViewall">An additional scenario comparing rivaroxaban with a mixed comparator was conducted&#46; For a lifetime horizon&#44; this analysis yielded an ICER of &#8364;9492&#47;LY and &#8364;6697&#47;QALY &#40;<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0025"></elsevierMultimedia></span></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Discussion</span><p id="par0155" class="elsevierStylePara elsevierViewall">In the present study&#44; an economic evaluation was undertaken to compare rivaroxaban to existing treatments for the prevention of stroke in patients with AF in Portugal from a societal perspective&#46; For this purpose&#44; a Markov model describing the management and consequences of AF and treatment was used&#46; The base-case analysis was based on ROCKET AF trial data&#46; Rivaroxaban was compared to warfarin&#44; which is the most widely used OAC and is recommended for AF patients with any additional risk factor for stroke in guidelines including those of the ESC and AHA&#47;ASA&#46; Patient population settings &#40;e&#46;g&#46; split by CHADS<span class="elsevierStyleInf">2</span> risk score and split between warfarin-na&#239;ve and warfarin-maintenance patients&#41; were based on the baseline characteristics of the ROCKET AF trial population&#46; Due to the fact that not all patients receive warfarin&#44; an additional analysis focused on real-world prescribing including a weighted average of warfarin&#44; aspirin and no treatment&#44; which better reflects Portuguese clinical practice&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Results from the base-case and scenario analyses&#44; using a societal perspective&#44; indicate that the ICER of rivaroxaban against the comparator varies between &#8364;3895&#47;QALY and &#8364;6697&#47;QALY respectively&#46; In the base-case scenario&#44; the drug acquisition costs of rivaroxaban were substantially higher than those of warfarin&#46; However&#44; this difference was largely compensated by the reduction in costs related to monitoring and events&#46; In the scenario analysis&#44; treatment costs are not offset&#44; but the efficacy of rivaroxaban leads to a substantial improvement in outcomes&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">As expected&#44; the OWSA indicated that the clinical efficacy of rivaroxaban is a strong driver of cost-effectiveness&#44; particularly the relative risk of major IC bleeding and ischemic stroke compared to warfarin&#46; Economic inputs describing the cost of warfarin monitoring were also important drivers&#46; Assuming a willingness-to-pay threshold of &#8364;30<span class="elsevierStyleHsp" style=""></span>000 per QALY&#44; the cost-effectiveness acceptability curve demonstrated that rivaroxaban had a high &#40;72&#37;&#41; probability of being cost-effective compared with warfarin only&#44; which is in line with results from previous analyses&#46; The results of both the OWSA and the PSA support the conclusion that the model is robust and that rivaroxaban is a cost-effective alternative to existing therapies for the prevention of stroke in non-valvular AF patients&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Markov models such as the one used to conduct the analyses presented in this study offer an opportunity to evaluate the impact of a health technology with respect to economics and health outcomes&#46; Nonetheless&#44; there were several limitations associated with this analysis&#46; The base-case analysis was based on data reported from an international randomized controlled clinical trial &#40;ROCKET AF&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> which is not necessarily representative of clinical practice in Portugal&#46; Additionally&#44; due to unavailability of Portuguese-specific data in terms of resource use&#44; an expert panel was consulted to provide estimates&#44; which introduces some uncertainty&#46; Lastly&#44; in the absence of Portuguese-specific utility values&#44; utilities from other European countries and the US were used in the analyses and were consequently less representative of the Portuguese population&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">This analysis can furthermore be deemed conservative since no disutility associated with warfarin treatment was applied&#46; Several studies have suggested that such a disutility exists&#46; Protheroe et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> showed that many AF patients would prefer not to receive warfarin therapy even if they meet the criteria for receiving it according to clinical guidelines&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">An economic evaluation of dabigatran for stroke prevention in patients with non-valvular AF in Portugal was recently published&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> A comparison between this evaluation and the study described in this paper is neither possible nor appropriate for several reasons&#44; including differences in modeling methods and in the composition of the comparators as well as the lack of head-to-head trials comparing rivaroxaban and dabigatran&#46; Additionally&#44; while an indirect comparison between rivaroxaban and dabigatran is possible&#44; the findings may not be robust given significant differences in the study populations and in study design&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">As previously mentioned&#44; there is evidence of extensive underprescribing of OACs even in patients with a high risk of stroke&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41&#44;42</span></a> In Portugal&#44; the challenge is two-fold&#58; firstly to increase the number of patients treated with OACs&#44; and secondly to improve health outcomes of patients on OACs&#46; The FAMA study concluded that 25&#37; of patients with AF in Portugal were not being adequately treated for this condition&#44; and that this proportion was even greater in patients aged 60 years or less&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> OACs were prescribed in slightly over a third of patients with AF&#44; a figure in line with published studies that have highlighted the underuse of these drugs in AF patients&#44; with 21&#46;8&#37; taking antiplatelets only&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> The results obtained show that the use of rivaroxaban offers opportunities to manage an unmet need for untreated patients and could reduce the stroke burden of an aging population&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conclusion</span><p id="par0190" class="elsevierStylePara elsevierViewall">This cost-effectiveness analysis demonstrated that rivaroxaban is cost-effective compared with VKA therapy in a trial-based setting&#44; and also compared to real-world antithrombotic prescribing in Portugal for stroke prophylaxis in patients with AF&#46; The drug acquisition costs of rivaroxaban were partially offset by savings in warfarin administration costs and savings in costs due to stroke and bleeding events&#44; such as IC bleeding&#46; The use of rivaroxaban in this therapeutic indication would help to decrease the disease burden for patients and for the Portuguese healthcare system&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Conflicts of interest</span><p id="par0330" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Ethical disclosures</span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Protection of human and animal subjects</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Confidentiality of data</span><p id="par0200" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Right to privacy and informed consent</span><p id="par0205" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span></span>"
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    "pdfFichero" => "main.pdf"
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    "fechaRecibido" => "2014-02-19"
    "fechaAceptado" => "2014-02-23"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec353052"
          "palabras" => array:5 [
            0 => "Atrial fibrillation"
            1 => "Cost-effectiveness"
            2 => "Portugal"
            3 => "Rivaroxaban"
            4 => "Stroke"
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          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec353051"
          "palabras" => array:5 [
            0 => "Fibrilha&#231;&#227;o Auricular"
            1 => "Custo-efetividade"
            2 => "Portugal"
            3 => "Rivaroxabano"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Introduction and Aims</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To project the long-term cost-effectiveness of treating non-valvular atrial fibrillation &#40;AF&#41; patients for stroke prevention with rivaroxaban compared to warfarin in Portugal&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A Markov model was used that included health and treatment states describing the management and consequences of AF and its treatment&#46; The model&#39;s time horizon was set at a patient&#39;s lifetime and each cycle at three months&#46; The analysis was conducted from a societal perspective and a 5&#37; discount rate was applied to both costs and outcomes&#46; Treatment effect data were obtained from the pivotal phase III ROCKET AF trial&#46; The model was also populated with utility values obtained from the literature and with cost data derived from official Portuguese sources&#46; The outcomes of the model included life-years&#44; quality-adjusted life-years &#40;QALYs&#41;&#44; incremental costs&#44; and associated incremental cost-effectiveness ratios &#40;ICERs&#41;&#46; Extensive sensitivity analyses were undertaken to further assess the findings of the model&#46; As there is evidence indicating underuse and underprescription of warfarin in Portugal&#44; an additional analysis was performed using a mixed comparator composed of no treatment&#44; aspirin&#44; and warfarin&#44; which better reflects real-world prescribing in Portugal&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This cost-effectiveness analysis produced an ICER of &#8364;3895&#47;QALY for the base-case analysis &#40;vs&#46; warfarin&#41; and of &#8364;6697&#47;QALY for the real-world prescribing analysis &#40;vs&#46; mixed comparator&#41;&#46; The findings were robust when tested in sensitivity analyses&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The results showed that rivaroxaban may be a cost-effective alternative compared with warfarin or real-world prescribing in Portugal&#46;</p>"
      ]
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Introdu&#231;&#227;o e objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Estimar o r&#225;cio custo-efetividade a longo-prazo associados &#224; utiliza&#231;&#227;o de rivaroxabano na preven&#231;&#227;o de acidente vascular cerebral em doentes com fibrilha&#231;&#227;o auricular &#40;FA&#41; n&#227;o-valvular relativamente a varfarina em Portugal&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Foi utilizado um modelo de Markov que representa os est&#225;dios representativos da progress&#227;o da FA e do seu tratamento&#46; O horizonte temporal modelizado descreve o tempo de vida dos doentes e cada ciclo tem a dura&#231;&#227;o de tr&#234;s meses&#46; A an&#225;lise foi desenvolvida na perspetiva da sociedade&#44; tendo sido aplicada uma taxa de atualiza&#231;&#227;o de cinco por cento para custos e consequ&#234;ncias&#46; Os efeitos do tratamento foram obtidos no ensaio cl&#237;nico de fase III ROCKET AF&#46; Adicionalmente&#44; no modelo foram inclu&#237;dos valores de utilidade provenientes da literatura e estimativas de custos nacionais&#46; Os <span class="elsevierStyleItalic">outcomes</span> avaliados no modelo incluem anos de vida incrementais&#44; anos de vida ajustados pela qualidade de vida incrementais &#40;AVAQ&#41;&#44; custos incrementais e r&#225;cio custo-efetividade incremental &#40;RCEI&#41;&#46; Foram desenvolvidas an&#225;lises de sensibilidade com o objetivo de avaliar os resultados do modelo&#46; A evid&#234;ncia existente indica subutiliza&#231;&#227;o e subprescri&#231;&#227;o de varfarina em Portugal e&#44; por esta raz&#227;o&#44; foi desenvolvida uma an&#225;lise adicional com um comparador misto&#44; constitu&#237;do por n&#227;o tratamento&#44; &#225;cido acetilsalic&#237;lico e varfarina&#44; o que reflete melhor o &#171;mundo real de prescri&#231;&#227;o&#187;&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">RCEI obtido varia entre 3 895&#8364;&#47;AVAQ para o cen&#225;rio-base &#40;relativamente varfarina&#41; e 6 697&#8364;&#47;AVAQ para o &#171;mundo real de prescri&#231;&#227;o&#187; &#40;relativamente comparador misto&#41;&#46; As an&#225;lises de sensibilidade demonstraram que os resultados s&#227;o robustos&#46;</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#227;o</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os resultados sugerem que rivaroxabano pode constituir uma alternativa custo-efetiva comparativamente a varfarina ou &#171;mundo real de prescri&#231;&#227;o&#187; em Portugal&#46;</p>"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Morais J&#44; Aguiar C&#44; McLeod E&#44; Chatzitheofilou I&#44; Fonseca Santos I&#44; Pereira S&#46; Estudo de custo-efectividade de rivaroxabano para preven&#231;&#227;o de acidente vascular cerebral em doentes com fibrilha&#231;&#227;o auricular em Portugal 2014&#46; Rev Port Cardiol&#46; 2014&#59;33&#58;535&#8211;544&#46;</p>"
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        "titulo" => "<span class="elsevierStyleSectionTitle" id="sect0065">List of abbreviations</span>"
        "listaDefinicion" => array:1 [
          0 => array:1 [
            "definicion" => array:24 [
              0 => array:2 [
                "termino" => "AF"
                "descripcion" => "<p id="par0210" class="elsevierStylePara elsevierViewall">atrial fibrillation</p>"
              ]
              1 => array:2 [
                "termino" => "AHA&#47;ASA"
                "descripcion" => "<p id="par0215" class="elsevierStylePara elsevierViewall">American Heart Association&#47;American Stroke Association</p>"
              ]
              2 => array:2 [
                "termino" => "CEA"
                "descripcion" => "<p id="par0220" class="elsevierStylePara elsevierViewall">cost-effectiveness analysis</p>"
              ]
              3 => array:2 [
                "termino" => "CHADS<span class="elsevierStyleInf">2</span>"
                "descripcion" => "<p id="par0225" class="elsevierStylePara elsevierViewall">congestive heart failure&#44; hypertension&#44; age &#8805;75&#44; diabetes&#44; stroke &#40;doubled&#41;</p>"
              ]
              4 => array:2 [
                "termino" => "CHA<span class="elsevierStyleInf">2</span>DS<span class="elsevierStyleInf">2</span>-VASc"
                "descripcion" => "<p id="par0230" class="elsevierStylePara elsevierViewall">congestive heart failure or left ventricular dysfunction&#44; hypertension&#44; age &#8805;75 &#40;doubled&#41;&#44; diabetes&#44; stroke &#40;doubled&#41;&#44; vascular disease&#44; age 65&#8211;74&#44; and sex category &#40;female&#41;</p>"
              ]
              5 => array:2 [
                "termino" => "CI"
                "descripcion" => "<p id="par0235" class="elsevierStylePara elsevierViewall">confidence interval</p>"
              ]
              6 => array:2 [
                "termino" => "CRNM"
                "descripcion" => "<p id="par0240" class="elsevierStylePara elsevierViewall">clinically relevant non-major</p>"
              ]
              7 => array:2 [
                "termino" => "EC"
                "descripcion" => "<p id="par0245" class="elsevierStylePara elsevierViewall">extracranial</p>"
              ]
              8 => array:2 [
                "termino" => "ESC"
                "descripcion" => "<p id="par0250" class="elsevierStylePara elsevierViewall">European Society of Cardiology</p>"
              ]
              9 => array:2 [
                "termino" => "FAMA"
                "descripcion" => "<p id="par0255" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Fibrilha&#231;&#227;o Auricular em Portugal</span> &#40;Atrial Fibrillation in Portugal&#41;</p>"
              ]
              10 => array:2 [
                "termino" => "HR"
                "descripcion" => "<p id="par0260" class="elsevierStylePara elsevierViewall">hazard ratio</p>"
              ]
              11 => array:2 [
                "termino" => "IC"
                "descripcion" => "<p id="par0265" class="elsevierStylePara elsevierViewall">intracranial</p>"
              ]
              12 => array:2 [
                "termino" => "ICER"
                "descripcion" => "<p id="par0270" class="elsevierStylePara elsevierViewall">incremental cost-effectiveness ratio</p>"
              ]
              13 => array:2 [
                "termino" => "INR"
                "descripcion" => "<p id="par0275" class="elsevierStylePara elsevierViewall">international normalized ratio</p>"
              ]
              14 => array:2 [
                "termino" => "LY"
                "descripcion" => "<p id="par0280" class="elsevierStylePara elsevierViewall">life-years</p>"
              ]
              15 => array:2 [
                "termino" => "MI"
                "descripcion" => "<p id="par0285" class="elsevierStylePara elsevierViewall">myocardial infarction</p>"
              ]
              16 => array:2 [
                "termino" => "NMA"
                "descripcion" => "<p id="par0290" class="elsevierStylePara elsevierViewall">network meta-analysis</p>"
              ]
              17 => array:2 [
                "termino" => "OACs"
                "descripcion" => "<p id="par0295" class="elsevierStylePara elsevierViewall">oral anticoagulants</p>"
              ]
              18 => array:2 [
                "termino" => "OWSA"
                "descripcion" => "<p id="par0300" class="elsevierStylePara elsevierViewall">one-way sensitivity analysis</p>"
              ]
              19 => array:2 [
                "termino" => "PSA"
                "descripcion" => "<p id="par0305" class="elsevierStylePara elsevierViewall">probabilistic sensitivity analysis</p>"
              ]
              20 => array:2 [
                "termino" => "QALYs"
                "descripcion" => "<p id="par0310" class="elsevierStylePara elsevierViewall">quality-adjusted life-years</p>"
              ]
              21 => array:2 [
                "termino" => "SE"
                "descripcion" => "<p id="par0315" class="elsevierStylePara elsevierViewall">systemic embolism</p>"
              ]
              22 => array:2 [
                "termino" => "SOT"
                "descripcion" => "<p id="par0320" class="elsevierStylePara elsevierViewall">safety on-treatment</p>"
              ]
              23 => array:2 [
                "termino" => "VKAs"
                "descripcion" => "<p id="par0325" class="elsevierStylePara elsevierViewall">vitamin K antagonists</p>"
              ]
            ]
          ]
        ]
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Overall model structure&#46; AF&#58; atrial fibrillation&#59; IC&#58; intracranial&#59; MI&#58; myocardial infarction&#59; Tx&#58; therapy&#46;</p>"
        ]
      ]
      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Cost-effectiveness acceptability curve base-case scenario &#8211; societal perspective&#46; CEAC&#58; cost-effectiveness acceptability curve&#59; QALY&#58; quality-adjusted life-years&#46;</p>"
        ]
      ]
      2 => array:7 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:2 [
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            0 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Event&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Baseline risk &#40;three months&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">RR rivaroxaban vs&#46; warfarin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Source&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Ischemic stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;36&#37; &#40;0&#46;27&#8211;0&#46;45&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;94 &#40;0&#46;75&#8211;1&#46;17&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;28&#37; &#40;0&#46;05&#8211;1&#46;22&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;81 &#40;0&#46;63&#8211;1&#46;06&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">SE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;05&#37; &#40;0&#46;00&#8211;0&#46;76&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;23 &#40;0&#46;09&#8211;0&#46;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Major IC bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;19&#37; &#40;0&#46;03&#8211;1&#46;04&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;67 &#40;0&#46;47&#8211;0&#46;93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Major EC bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;69&#37; &#40;0&#46;24&#8211;1&#46;90&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;14 &#40;0&#46;98&#8211;1&#46;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CRNM bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;97&#37; &#40;1&#46;79&#8211;5&#46;05&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;04 &#40;0&#46;96&#8211;1&#46;13&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab566025.png"
              ]
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Safety-on-treatment analysis&#46; CRNM&#58; clinically relevant non-major&#59; EC&#58; extracranial&#59; IC&#58; intracranial&#59; MI&#58; myocardial infarction&#59; RR&#58; relative risk&#59; SE&#58; systemic embolism&#46;</p>"
            ]
          ]
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Overview of assumed clinical parameters and values in the base case&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CI&#58; confidence interval&#59; EC&#58; extracranial&#59; IC&#58; intracranial&#59; MI&#58; myocardial infarction&#59; SOT&#58; safety-on-treatment&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Health state&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Three-month mortality &#40;95&#37; CI&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Source&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Major stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12&#46;60 &#40;9&#46;40&#8211;15&#46;70&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF &#40;SOT&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-major stroke&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;63 &#40;0&#46;91&#8211;13&#46;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Marini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Major EC bleed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;55 &#40;1&#46;16&#8211;1&#46;94&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF &#40;SOT&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IC bleed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38&#46;80 &#40;29&#46;14&#8211;48&#46;56&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF &#40;SOT&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-IC bleed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;63 &#40;0&#46;91&#8211;13&#46;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Marini et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&#46;69 &#40;7&#46;27&#8211;12&#46;11&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ROCKET AF &#40;SOT&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Post-MI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;68 &#40;0&#46;00&#8211;6&#46;75&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Hoit et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab566024.png"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Mortality rates&#46;</p>"
        ]
      ]
      4 => array:7 [
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        "tipo" => "MULTIMEDIATABLA"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">CRNM&#58; clinically relevant non-major&#59; EC&#58; extracranial&#59; IC&#58; intracranial&#59; MI&#58; myocardial infarction&#59; SE&#58; systemic embolism&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Event&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Total cost &#40;&#8364;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Acquisition</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rivaroxaban &#8211; 20 mg or 15 mg once daily</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Warfarin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211; loading dose&#58; 5 mg once daily</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211; maintenance dose&#58; 3&#46;75 mg once daily</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Aspirin &#8211; 100&#8211;150 mg once daily</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Monitoring visits</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Rivaroxaban</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">105&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Warfarin</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">First visit</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">148&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Subsequent visits</span></td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">General physician&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Specialist&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Ischemic stroke &#40;cost per cycle&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Minor ischemic stroke</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1270&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Major ischemic stroke</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1989&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rehabilitation &#40;per day&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Long-term follow-up</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">392&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Bleedings</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>CRNM bleeding</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">150&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Major EC bleeding</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2425&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " rowspan="3" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>IC bleeding</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Acute</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2628&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Rehabilitation &#40;per day&#41;</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="2" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Long-term follow-up</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">462&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">SE &#40;per cycle&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acute&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2603&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " colspan="4" align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">MI &#40;per cycle&#41;</span></td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Acute event&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7270&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Long-term follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">802&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Overview of drug acquisition&#44; drug monitoring and event costs from a societal perspective&#46;</p>"
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ICER&#58; incremental cost-effectiveness ratio&#59; LY&#58; life-year&#59; QALY&#58; quality-adjusted life-year&#46; All values have been rounded up&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Rivaroxaban&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Warfarin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Difference&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total costs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;6142&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;6061&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Drug acquisition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;3267&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;3152&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Drug administration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;695&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;3484&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;&#8364;2789&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Event treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;2425&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;2585&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;&#8364;160&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total LYs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;023&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total QALYs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;81&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;021&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICER &#40;&#8364;&#47;LY&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;3494&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICER &#40;&#8364;&#47;QALY&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;3895&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">ICER&#58; incremental cost-effectiveness ratio&#59; LY&#58; life-year&#59; QALY&#58; quality-adjusted life-year&#46;</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Rivaroxaban&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Mixed comparator&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Difference&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;6835&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;6278&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;557&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Drug acquisition&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;3267&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#8364;109&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Drug administration&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;695&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;2279&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8722;&#8364;1585&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Event treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;2425&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;2935&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">&#8722;&#8364;510&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total LYs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#46;97&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">4&#46;91&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;059&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Total QALYs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46;68&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;083&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICER &#40;&#8364;&#47;LY&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;9433&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">ICER &#40;&#8364;&#47;QALY&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8211;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8364;6697&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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