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Cost-effectiveness of rivaroxaban for stroke prevention in atrial fibrillation in the Portuguese setting
Estudo de custo-efectividade de rivaroxabano para prevenção de acidente vascular cerebral em doentes com fibrilhação auricular em Portugal
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class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Hospital de Santo André, CHLP, Leiria, Portugal" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Hospital de Santa Cruz, CHLO, Carnaxide, Portugal" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "IMS Health, London, United Kingdom" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Bayer Portugal, S.A., Carnaxide, Portugal" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Estudo de custo-efectividade de rivaroxabano para prevenção de acidente vascular cerebral em doentes com fibrilhação auricular em Portugal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1803 "Ancho" => 2922 "Tamanyo" => 341125 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Overall model structure. AF: atrial fibrillation; IC: intracranial; MI: myocardial infarction; Tx: therapy.</p>" ] ] ] "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 (AF) is the most common sustained cardiac rhythm disorder and constitutes an important risk factor for stroke,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> associated with a five-fold risk<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a>: 15% of all strokes are attributable to AF and around 25% of patients with ischemic stroke present AF.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The prevalence of AF in the general population in developed countries is approximately 1.5–2%. In addition, the mean age of patients with this condition is steadily rising, such that it now averages between 75 and 85 years.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> According to the FAMA (Atrial Fibrillation in Portugal) study, the prevalence of AF in the Portuguese population aged 40 and over is 2.5% (95% confidence interval [CI]: 2.2–2.8%) and increases with age, reaching 6.6% for individuals aged 70–79, and 10.4% for those aged 80 or more.<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, with the intention of achieving the best outcome for the AF patient. The clinical guidelines on antithrombotic therapy for AF issued by the Portuguese National Coordinating Body for Cardiovascular Disease,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> the European Society of Cardiology (ESC)<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and the American Heart Association/American Stroke Association (AHA/ASA)<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> are generally accepted by the Portuguese medical community. Overall, these guidelines consider oral anticoagulants (OACs) the cornerstone of thromboembolic prevention in AF. Vitamin K antagonists (VKAs), primarily warfarin, are widely regarded as the current standard of care.</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% vs. placebo.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> Although effective, VKAs have limitations that make patient management challenging in practice.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> For instance, the anticoagulation response to VKA treatment is unpredictable and is affected by genetic and environmental factors such as drug-drug and food-drug interactions. The high inter- and intra-patient variability in response to therapy means that frequent blood tests for international normalized ratio (INR) monitoring (an INR 2.0–3.0 is recommended) and dose adjustments are necessary.<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, when used as studied in the clinical trials performed to date.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Over the past decade, risk factor scoring systems have been widely used to stratify the risk of thromboembolism in non-valvular AF. The simplest risk assessment scheme is the CHADS<span class="elsevierStyleInf">2</span> score (congestive heart failure, hypertension, age ≥75, diabetes, stroke [doubled]).<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 (congestive heart failure or left ventricular dysfunction, hypertension, age ≥75 [doubled], diabetes, stroke [doubled], vascular disease, age 65–74, and sex category [female]), which considers additional risk factors, more accurately identifies patients at very low risk for stroke and is recommended in the ESC 2012 guidelines.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Rivaroxaban (Xarelto<span class="elsevierStyleSup">®</span>) is a new OAC; it is a highly selective, oral, once daily, direct factor Xa inhibitor. Rivaroxaban has predictable pharmacokinetics and pharmacodynamics, few relevant drug interactions, and does not require monitoring of coagulation parameters.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The efficacy and tolerability of rivaroxaban for prevention of stroke and systemic embolism (SE) in AF patients has been compared with warfarin in the ROCKET AF (Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial. ROCKET AF is a multinational, phase III, randomized, double-blind, multicenter, event-driven study, involving 14 264 patients in whom treatment with OACs was recommended. In the primary analysis, rivaroxaban demonstrated a 21% risk reduction in event rate for stroke and SE (hazard ratio [HR] 0.79, 95% CI 0.66–0.96, p<0.001 for non-inferiority in the per-protocol, as-treated population and HR 0.79; 95% CI 0.65–0.95, p=0.02 for superiority in the safety, as-treated population) compared with warfarin. Additionally, rates of intracranial (IC) bleeding, fatal bleeding and bleeding at critical anatomical sites were significantly lower in the rivaroxaban treatment arm compared to the warfarin treatment arm (HR: 0.67, 95% CI [0.47–0.93], p<0.02 for IC bleeding; 0.50 [0.31–0.79], p=0.003 for fatal bleeding and 0.69 [0.53–0.91], p=0.007 for bleeding at critical anatomical sites). <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, including the introduction of a reference pricing system, administrative price reductions, and various changes in co-payment regulations.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In the context of an economic crisis, health economic evaluations such as cost-effectiveness analyses (CEAs) can be useful tools to inform resource allocation decisions in a systematic, transparent and efficient manner. The main outcome of a CEA is an estimate of the costs and effects associated with the new technology compared with alternative treatment(s) such as standard of care, in order to indicate whether the new treatment provides good value for money to the health care payer. Hence, the main aim of this study was to undertake a CEA comparing rivaroxaban with warfarin for stroke prevention in patients with non-valvular AF. An additional analysis in which rivaroxaban was compared with real-world prescribing (no treatment, aspirin and warfarin) was performed, since the existing evidence indicates underuse and underprescription of warfarin in Portugal. This model supported the reimbursement request for rivaroxaban in Portugal in this therapeutic indication.</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. The analysis was conducted using a previously described economic model.<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. The outcomes of the model included incremental life-years (LYs), incremental quality-adjusted life years (QALYs), incremental costs, and incremental cost-effectiveness ratios (ICERs) expressed in terms of €/LY gained and €/QALY gained. The base-case analysis was conducted from a societal perspective using direct costs only. The model's time horizon was set at a patient's lifetime in order to fully incorporate the costs and consequences of AF. The mean age of patients in the model was set to 73 years and the lifetime horizon was therefore set to 20 years. Costs and outcomes were discounted at a 5% annual rate, in accordance with the most recent recommendations for economic evaluations published in Portugal.<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: patients suffering from non-valvular AF with a CHADS<span class="elsevierStyleInf">2</span> score ≥2 (mean CHADS<span class="elsevierStyleInf">2</span> score 3.5), of whom 62.5% had previously been treated with VKAs. Based on the opinion of an expert panel, management of VKA treatment was assumed to be undertaken primarily in a specialist setting (65% of patients), with the remaining patients (35%) managed in a primary care setting.</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. A cycle length of three months was deemed short enough to adequately capture the frequency of major events. Patients entered the model with stable uncomplicated AF and received treatment with either rivaroxaban (20 mg oral tablet, once daily) or dose-adjusted warfarin (target INR of 2.0–3.0). Patients who discontinued treatment were assumed to receive aspirin irrespective of initial treatment.</p><p id="par0060" class="elsevierStylePara elsevierViewall">In the model, patients were assumed to be always at risk of major complications unless they were currently experiencing an acute event in the same cycle. Major complications considered in this model included ischemic stroke, either minor or major, SE, myocardial infarction (MI) and bleeding. Bleeding events were categorized as major extracranial (EC), major intracranial (IC) or clinically relevant non-major (CRNM) as defined in the description of the rationale and design of the ROCKET AF trial.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Major events were classified as transient or with permanent after-effects (<a class="elsevierStyleCrossRef" href="#fig0005">Figure 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Boxed events were considered permanent while non-boxed events were considered transient. Each health state had a cost and utility weight describing associated quality of life as a pay-off.</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, patients move from one health state to another with particular probabilities referred to as transition probabilities; these are primarily derived from clinical trials. In the base-case analysis, baseline event rates (i.e. the probability of moving from one health state to another) were obtained from the warfarin treatment arm of the ROCKET AF trial. Relative treatment effects describing the efficacy and safety of rivaroxaban vs. warfarin for the prevention of stroke and SE were then applied to these baseline event rates (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</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. Given that limited data for real-life persistence were available for rivaroxaban, the model used discontinuation rates for the initial cycle of 8.9% and 8.0% for rivaroxaban and warfarin, respectively, from the ROCKET AF trial. In subsequent cycles it was 4.39% and 4.46%, respectively. In the model, patients who had discontinued treatment transitioned into a mirror health state. Patients who discontinued were assumed to switch treatment to aspirin.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Mortality</span><p id="par0080" class="elsevierStylePara elsevierViewall">In the model, mortality was accounted for in two ways: by considering age-adjusted mortality rates from the Portuguese general population and by capturing event-related mortality. For general population mortality rates, life tables published by the Portuguese National Institute of Statistics<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> were used. In addition, after experiencing a major ischemic stroke, major bleeding event (EC or IC) or MI, it was assumed that patients may die with a probability equal to the case-fatality rate observed in ROCKET AF. Minor ischemic stroke, SE and CRNM bleeding events were assumed to have no associated case fatality. Patients who had experienced a major ischemic stroke or MI were assumed to have an increased mortality rate, despite recovery from the acute episode, as the evidence shows extended impact on life expectancy. Since post-recovery mortality data were not available from the ROCKET AF trial, these mortality rates were derived from the literature.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5,20</span></a> For post-IC bleeding, since no mortality rates were identified in the literature, 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> (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</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.<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. The generic outcome is usually expressed using QALYs. 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. Due to a lack of Portuguese-specific utility values, this analysis incorporated utility values from a combination of studies in the international literature. A utility value of 0.779 was assigned to stable AF patients.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> Utility values of 0.189, 0.641 and 0.660 were assigned for the health states of major ischemic stroke, 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, while the values 0.482 and 0.719 were considered for post major ischemic stroke and post minor ischemic stroke.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Finally, utility values of 0.776 and 0.598 were assigned for CRNM and major EC bleeding, respectively.<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. The following direct costs were considered: drug acquisition, drug monitoring costs and event-related costs. All costs were expressed in 2011 euros.</p><p id="par0095" class="elsevierStylePara elsevierViewall">Unit costs were obtained from published Portuguese official sources, namely Orders in Council (<span class="elsevierStyleItalic">Portaria</span> no. 139/2009<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> and <span class="elsevierStyleItalic">Portaria</span> no. 220/2011<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a>) and reports issued by the Central Administration of the National Health System (NHS) (Analytical Accounts of NHS hospitals<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a>).</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's INFOMED database.<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. Monitoring cost differed according to setting of care (general physician or specialist). In clinical practice, when patients begin warfarin for the first time, or after a period without taking it, regular INR monitoring by a physician is recommended. Based on the expert panel's opinion, during the first three months of warfarin treatment it was assumed that patients required seven monitoring visits. Thereafter, patients required 3.5 monitoring visits per cycle, based on the findings of a Portuguese study.<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, 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.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Costs were assigned to acute events and to those with long-term sequelae. The most severe events, such as ischemic stroke and major IC bleeding, were modeled using multiple components for calculating the acute costs. Besides the cost of acute treatment, long-term costs associated with an acute event, such as its impact on functional status, were also considered by including a cost for rehabilitation. 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 (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</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, an ICER was derived by dividing the incremental costs by the incremental LYs or QALYs gained with rivaroxaban compared to warfarin. Unlike several countries, such as the United Kingdom, the Portuguese Health Authority (INFARMED) does not use an explicit willingness-to-pay threshold when assessing ICERs.</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.<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: a one-way sensitivity analysis (OWSA) was carried out in order to identify the key drivers of cost-effectiveness and a probabilistic sensitivity analysis (PSA) was performed to test the overall robustness of the model.</p><p id="par0125" class="elsevierStylePara elsevierViewall">In the OWSA, the base-case value of parameters was varied using low and high values within plausible ranges. For parameters such as clinical efficacy values, the reported 95% CIs from the ROCKET AF trial were used. The base-case value of cost inputs were varied by ±25%, which was considered sufficient variation to capture the relevant uncertainty. PSA is a stochastic analysis conducted to test second-order uncertainty in the model. In this analysis 500 simulations were run, each time varying all model parameters carrying second-order uncertainty within logical ranges.</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,<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6,32</span></a> an additional analysis was conducted using a mixed comparator composed of no treatment (6%), aspirin (44%) and warfarin (50%), which better reflects real-world prescribing in the Portuguese setting. The composition of this mixed comparator was based on the literature<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33–36</span></a> and expert opinion. 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% CHADS<span class="elsevierStyleInf">2</span> risk score of 2 and 70% CHADS<span class="elsevierStyleInf">2</span> risk score of 3 or higher. Among warfarin patients, 25% were considered warfarin-naïve. Relative treatment effects describing the efficacy of rivaroxaban vs. the mixed comparator for the prevention of stroke, SE, bleeding and MI were based on results from a network meta-analysis (NMA). This NMA was conducted to allow comparison of rivaroxaban with non-VKA comparators, which were not included in the ROCKET AF trial. Baseline event rates were set as the placebo arms of clinical trials used in the NMA.<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's lifetime horizon, and compared with warfarin, rivaroxaban was projected to be associated with an additional cost of €81 as well as with a gain of 0.023 LYs and 0.021 QALYs, resulting in an ICER of €3494/LY and €3895/QALY. Assuming a €30 000/QALY willingness-to-pay threshold, rivaroxaban is deemed a cost-effective alternative compared to warfarin (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>).</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, particularly discontinuation and subsequent discontinuation rate for rivaroxaban and relative risk for rivaroxaban vs. warfarin for stroke. Additional analyses were run assuming shorter time horizons (10 and 15 years) and, as expected, marginally higher ICERs were obtained: €4286/QALY for a 10-year time horizon and €3910/QALY for a 15-year time horizon.</p><p id="par0145" class="elsevierStylePara elsevierViewall">The results of the PSA confirmed the overall robustness of the base-case analysis. The cost-effectiveness acceptability curve showed that at a willingness-to-pay threshold of €30 000/QALY, the likelihood of rivaroxaban being cost-effective compared to warfarin was 72% (<a class="elsevierStyleCrossRef" href="#fig0010">Figure 2</a>).</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. For a lifetime horizon, this analysis yielded an ICER of €9492/LY and €6697/QALY (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>).</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, 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. For this purpose, a Markov model describing the management and consequences of AF and treatment was used. The base-case analysis was based on ROCKET AF trial data. Rivaroxaban was compared to warfarin, 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/ASA. Patient population settings (e.g. split by CHADS<span class="elsevierStyleInf">2</span> risk score and split between warfarin-naïve and warfarin-maintenance patients) were based on the baseline characteristics of the ROCKET AF trial population. Due to the fact that not all patients receive warfarin, an additional analysis focused on real-world prescribing including a weighted average of warfarin, aspirin and no treatment, which better reflects Portuguese clinical practice.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Results from the base-case and scenario analyses, using a societal perspective, indicate that the ICER of rivaroxaban against the comparator varies between €3895/QALY and €6697/QALY respectively. In the base-case scenario, the drug acquisition costs of rivaroxaban were substantially higher than those of warfarin. However, this difference was largely compensated by the reduction in costs related to monitoring and events. In the scenario analysis, treatment costs are not offset, but the efficacy of rivaroxaban leads to a substantial improvement in outcomes.</p><p id="par0165" class="elsevierStylePara elsevierViewall">As expected, the OWSA indicated that the clinical efficacy of rivaroxaban is a strong driver of cost-effectiveness, particularly the relative risk of major IC bleeding and ischemic stroke compared to warfarin. Economic inputs describing the cost of warfarin monitoring were also important drivers. Assuming a willingness-to-pay threshold of €30<span class="elsevierStyleHsp" style=""></span>000 per QALY, the cost-effectiveness acceptability curve demonstrated that rivaroxaban had a high (72%) probability of being cost-effective compared with warfarin only, which is in line with results from previous analyses. 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.</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. Nonetheless, there were several limitations associated with this analysis. The base-case analysis was based on data reported from an international randomized controlled clinical trial (ROCKET AF),<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> which is not necessarily representative of clinical practice in Portugal. Additionally, due to unavailability of Portuguese-specific data in terms of resource use, an expert panel was consulted to provide estimates, which introduces some uncertainty. Lastly, in the absence of Portuguese-specific utility values, utilities from other European countries and the US were used in the analyses and were consequently less representative of the Portuguese population.</p><p id="par0175" class="elsevierStylePara elsevierViewall">This analysis can furthermore be deemed conservative since no disutility associated with warfarin treatment was applied. Several studies have suggested that such a disutility exists. Protheroe et al.<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.</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.<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, 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. Additionally, while an indirect comparison between rivaroxaban and dabigatran is possible, the findings may not be robust given significant differences in the study populations and in study design.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">As previously mentioned, there is evidence of extensive underprescribing of OACs even in patients with a high risk of stroke.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">41,42</span></a> In Portugal, the challenge is two-fold: firstly to increase the number of patients treated with OACs, and secondly to improve health outcomes of patients on OACs. The FAMA study concluded that 25% of patients with AF in Portugal were not being adequately treated for this condition, and that this proportion was even greater in patients aged 60 years or less.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> OACs were prescribed in slightly over a third of patients with AF, a figure in line with published studies that have highlighted the underuse of these drugs in AF patients, with 21.8% taking antiplatelets only.<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.</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, and also compared to real-world antithrombotic prescribing in Portugal for stroke prophylaxis in patients with AF. 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, such as IC bleeding. The use of rivaroxaban in this therapeutic indication would help to decrease the disease burden for patients and for the Portuguese healthcare system.</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.</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.</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.</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.</p></span></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:2 [ "identificador" => "xres373485" "titulo" => array:5 [ 0 => "Abstract" 1 => "Introduction and Aims" 2 => "Methods" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec352584" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres373484" "titulo" => array:5 [ 0 => "Resumo" 1 => "Introdução e objetivos" 2 => "Métodos" 3 => "Resultados" 4 => "Conclusão" ] ] 3 => array:2 [ "identificador" => "xpalclavsec352583" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Model overview" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Patient population" ] 2 => array:3 [ "identificador" => "sec0025" "titulo" => "Model structure" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Model health states" ] ] ] 3 => array:3 [ "identificador" => "sec0035" "titulo" => "Model input data" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Efficacy and safety data" ] 1 => array:2 [ "identificador" => "sec0045" "titulo" => "Persistence and discontinuation rate" ] 2 => array:2 [ "identificador" => "sec0050" "titulo" => "Mortality" ] 3 => array:2 [ "identificador" => "sec0055" "titulo" => "Utility values" ] 4 => array:2 [ "identificador" => "sec0060" "titulo" => "Data on costs and resource use" ] ] ] 4 => array:3 [ "identificador" => "sec0065" "titulo" => "Analyses performed" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Base-case analyses" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Sensitivity analyses" ] 2 => array:2 [ "identificador" => "sec0080" "titulo" => "Scenario analysis" ] ] ] ] ] 6 => array:3 [ "identificador" => "sec0085" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0090" "titulo" => "Base-case analysis" ] 1 => array:2 [ "identificador" => "sec0095" "titulo" => "Sensitivity analyses" ] 2 => array:2 [ "identificador" => "sec0100" "titulo" => "Scenario analysis" ] ] ] 7 => array:2 [ "identificador" => "sec0105" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0110" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0135" "titulo" => "Conflicts of interest" ] 10 => array:3 [ "identificador" => "sec0115" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0120" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0125" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0130" "titulo" => "Right to privacy and informed consent" ] ] ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-02-19" "fechaAceptado" => "2014-02-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec352584" "palabras" => array:5 [ 0 => "Atrial fibrillation" 1 => "Cost-effectiveness" 2 => "Portugal" 3 => "Rivaroxaban" 4 => "Stroke" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec352583" "palabras" => array:5 [ 0 => "Fibrilhação Auricular" 1 => "Custo-efetividade" 2 => "Portugal" 3 => "Rivaroxabano" 4 => "AVC" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "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 (AF) patients for stroke prevention with rivaroxaban compared to warfarin in Portugal.</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. The model's time horizon was set at a patient's lifetime and each cycle at three months. The analysis was conducted from a societal perspective and a 5% discount rate was applied to both costs and outcomes. Treatment effect data were obtained from the pivotal phase III ROCKET AF trial. The model was also populated with utility values obtained from the literature and with cost data derived from official Portuguese sources. The outcomes of the model included life-years, quality-adjusted life-years (QALYs), incremental costs, and associated incremental cost-effectiveness ratios (ICERs). Extensive sensitivity analyses were undertaken to further assess the findings of the model. As there is evidence indicating underuse and underprescription of warfarin in Portugal, an additional analysis was performed using a mixed comparator composed of no treatment, aspirin, and warfarin, which better reflects real-world prescribing in Portugal.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This cost-effectiveness analysis produced an ICER of €3895/QALY for the base-case analysis (vs. warfarin) and of €6697/QALY for the real-world prescribing analysis (vs. mixed comparator). The findings were robust when tested in sensitivity analyses.</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.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Introdução e objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Estimar o rácio custo-efetividade a longo-prazo associados à utilização de rivaroxabano na prevenção de acidente vascular cerebral em doentes com fibrilhação auricular (FA) não-valvular relativamente a varfarina em Portugal.</p> <span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Foi utilizado um modelo de Markov que representa os estádios representativos da progressão da FA e do seu tratamento. O horizonte temporal modelizado descreve o tempo de vida dos doentes e cada ciclo tem a duração de três meses. A análise foi desenvolvida na perspetiva da sociedade, tendo sido aplicada uma taxa de atualização de cinco por cento para custos e consequências. Os efeitos do tratamento foram obtidos no ensaio clínico de fase III ROCKET AF. Adicionalmente, no modelo foram incluídos valores de utilidade provenientes da literatura e estimativas de custos nacionais. Os <span class="elsevierStyleItalic">outcomes</span> avaliados no modelo incluem anos de vida incrementais, anos de vida ajustados pela qualidade de vida incrementais (AVAQ), custos incrementais e rácio custo-efetividade incremental (RCEI). Foram desenvolvidas análises de sensibilidade com o objetivo de avaliar os resultados do modelo. A evidência existente indica subutilização e subprescrição de varfarina em Portugal e, por esta razão, foi desenvolvida uma análise adicional com um comparador misto, constituído por não tratamento, ácido acetilsalicílico e varfarina, o que reflete melhor o «mundo real de prescrição».</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">RCEI obtido varia entre 3 895€/AVAQ para o cenário-base (relativamente varfarina) e 6 697€/AVAQ para o «mundo real de prescrição» (relativamente comparador misto). As análises de sensibilidade demonstraram que os resultados são robustos.</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusão</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Os resultados sugerem que rivaroxabano pode constituir uma alternativa custo-efetiva comparativamente a varfarina ou «mundo real de prescrição» em Portugal.</p>" ] ] "nomenclatura" => array:1 [ 0 => array:3 [ "identificador" => "nom0005" "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/ASA" "descripcion" => "<p id="par0215" class="elsevierStylePara elsevierViewall">American Heart Association/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, hypertension, age ≥75, diabetes, stroke (doubled)</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, hypertension, age ≥75 (doubled), diabetes, stroke (doubled), vascular disease, age 65–74, and sex category (female)</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">Fibrilhação Auricular em Portugal</span> (Atrial Fibrillation in Portugal)</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>" ] ] ] ] ] ] "multimedia" => array:7 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1803 "Ancho" => 2922 "Tamanyo" => 341125 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Overall model structure. AF: atrial fibrillation; IC: intracranial; MI: myocardial infarction; Tx: therapy.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1284 "Ancho" => 2167 "Tamanyo" => 101664 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Cost-effectiveness acceptability curve base-case scenario – societal perspective. CEAC: cost-effectiveness acceptability curve; QALY: quality-adjusted life-years.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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">Event \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 (three months) \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. warfarin \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 \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 \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">0.36% (0.27–0.45) \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">0.94 (0.75–1.17) \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> \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 \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">0.28% (0.05–1.22) \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">0.81 (0.63–1.06) \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> \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 \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">0.05% (0.00–0.76) \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">0.23 (0.09–0.61) \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> \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 \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">0.19% (0.03–1.04) \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">0.67 (0.47–0.93) \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> \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 \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">0.69% (0.24–1.90) \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">1.14 (0.98–1.33) \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> \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 \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">2.97% (1.79–5.05) \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">1.04 (0.96–1.13) \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> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab565126.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Safety-on-treatment analysis. CRNM: clinically relevant non-major; EC: extracranial; IC: intracranial; MI: myocardial infarction; RR: relative risk; SE: systemic embolism.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Overview of assumed clinical parameters and values in the base case.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">CI: confidence interval; EC: extracranial; IC: intracranial; MI: myocardial infarction; SOT: safety-on-treatment.</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 \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 (95% CI) \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 \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 \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">12.60 (9.40–15.70%) \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 (SOT) \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 \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">2.63 (0.91–13.50%) \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.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> \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 \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">1.55 (1.16–1.94%) \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 (SOT) \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 \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">38.80 (29.14–48.56%) \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 (SOT) \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 \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">2.63 (0.91–13.50%) \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.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> \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 \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">9.69 (7.27–12.11%) \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 (SOT) \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 \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">2.68 (0.00–6.75%) \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.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab565125.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Mortality rates.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">CRNM: clinically relevant non-major; EC: extracranial; IC: intracranial; MI: myocardial infarction; SE: systemic embolism.</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">Event \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"> \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"> \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 (€) \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 – 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">2.65 \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 \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">– loading dose: 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">0.06 \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"> \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">– maintenance dose: 3.75 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">0.05 \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 – 100–150 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">0.10 \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 \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> \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"> \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 \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 \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 \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 \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 \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 (cost per cycle)</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 \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 \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 (per day)</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 \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 \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 \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 \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 \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 (per day)</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 \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 \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 (per cycle)</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 \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"> \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"> \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 \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 (per cycle)</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 \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"> \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"> \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 \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 \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"> \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"> \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 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab565124.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Overview of drug acquisition, drug monitoring and event costs from a societal perspective.</p>" ] ] 5 => array:7 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">ICER: incremental cost-effectiveness ratio; LY: life-year; QALY: quality-adjusted life-year. All values have been rounded up.</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"> \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 \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 \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 \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 \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">€6142 \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">€6061 \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">€81 \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 \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">€3267 \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">€114 \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">€3152 \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 \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">€695 \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">€3484 \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">−€2789 \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 \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">€2425 \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">€2585 \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">−€160 \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 \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">5.00 \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">4.98 \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">0.023 \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 \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">3.83 \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">3.81 \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">0.021 \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 (€/LY) \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">– \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">– \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">€3494 \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 (€/QALY) \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">– \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">– \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">€3895 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab565128.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Cost-effectiveness results of base-case analysis.</p>" ] ] 6 => array:7 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">ICER: incremental cost-effectiveness ratio; LY: life-year; QALY: quality-adjusted life-year.</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"> \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 \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">Mixed comparator \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 \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 \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">€6835 \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">€6278 \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">€557 \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 \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">€3267 \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">€109 \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">€3158 \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 \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">€695 \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">€2279 \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">−€1585 \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 \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">€2425 \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">€2935 \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">−€510 \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 \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">4.97 \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">4.91 \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">0.059 \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 \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">3.76 \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">3.68 \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">0.083 \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 (€/LY) \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">– \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">– \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">€9433 \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 (€/QALY) \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">– \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">– \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">€6697 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab565127.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">Cost-effectiveness results of additional scenario analysis.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:42 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation-executive 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| Ano/Mês | Html | Total | |
|---|---|---|---|
| 2024 Novembro | 6 | 6 | 12 |
| 2024 Outubro | 58 | 20 | 78 |
| 2024 Setembro | 98 | 26 | 124 |
| 2024 Agosto | 67 | 27 | 94 |
| 2024 Julho | 38 | 32 | 70 |
| 2024 Junho | 54 | 22 | 76 |
| 2024 Maio | 57 | 24 | 81 |
| 2024 Abril | 57 | 30 | 87 |
| 2024 Maro | 60 | 18 | 78 |
| 2024 Fevereiro | 38 | 20 | 58 |
| 2024 Janeiro | 34 | 25 | 59 |
| 2023 Dezembro | 31 | 36 | 67 |
| 2023 Novembro | 40 | 22 | 62 |
| 2023 Outubro | 28 | 13 | 41 |
| 2023 Setembro | 34 | 18 | 52 |
| 2023 Agosto | 42 | 20 | 62 |
| 2023 Julho | 28 | 10 | 38 |
| 2023 Junho | 36 | 10 | 46 |
| 2023 Maio | 42 | 22 | 64 |
| 2023 Abril | 32 | 3 | 35 |
| 2023 Maro | 61 | 21 | 82 |
| 2023 Fevereiro | 38 | 18 | 56 |
| 2023 Janeiro | 45 | 14 | 59 |
| 2022 Dezembro | 55 | 22 | 77 |
| 2022 Novembro | 79 | 23 | 102 |
| 2022 Outubro | 42 | 26 | 68 |
| 2022 Setembro | 34 | 34 | 68 |
| 2022 Agosto | 40 | 25 | 65 |
| 2022 Julho | 70 | 45 | 115 |
| 2022 Junho | 76 | 25 | 101 |
| 2022 Maio | 50 | 26 | 76 |
| 2022 Abril | 57 | 29 | 86 |
| 2022 Maro | 47 | 37 | 84 |
| 2022 Fevereiro | 44 | 16 | 60 |
| 2022 Janeiro | 42 | 26 | 68 |
| 2021 Dezembro | 24 | 40 | 64 |
| 2021 Novembro | 46 | 36 | 82 |
| 2021 Outubro | 34 | 42 | 76 |
| 2021 Setembro | 28 | 29 | 57 |
| 2021 Agosto | 32 | 25 | 57 |
| 2021 Julho | 17 | 24 | 41 |
| 2021 Junho | 24 | 26 | 50 |
| 2021 Maio | 23 | 28 | 51 |
| 2021 Abril | 68 | 47 | 115 |
| 2021 Maro | 68 | 25 | 93 |
| 2021 Fevereiro | 52 | 21 | 73 |
| 2021 Janeiro | 48 | 12 | 60 |
| 2020 Dezembro | 31 | 13 | 44 |
| 2020 Novembro | 36 | 18 | 54 |
| 2020 Outubro | 28 | 18 | 46 |
| 2020 Setembro | 55 | 9 | 64 |
| 2020 Agosto | 33 | 15 | 48 |
| 2020 Julho | 58 | 11 | 69 |
| 2020 Junho | 52 | 8 | 60 |
| 2020 Maio | 85 | 8 | 93 |
| 2020 Abril | 72 | 13 | 85 |
| 2020 Maro | 60 | 12 | 72 |
| 2020 Fevereiro | 91 | 23 | 114 |
| 2020 Janeiro | 31 | 4 | 35 |
| 2019 Dezembro | 43 | 6 | 49 |
| 2019 Novembro | 44 | 11 | 55 |
| 2019 Outubro | 33 | 6 | 39 |
| 2019 Setembro | 99 | 7 | 106 |
| 2019 Agosto | 35 | 8 | 43 |
| 2019 Julho | 34 | 12 | 46 |
| 2019 Junho | 40 | 16 | 56 |
| 2019 Maio | 44 | 9 | 53 |
| 2019 Abril | 40 | 16 | 56 |
| 2019 Maro | 119 | 11 | 130 |
| 2019 Fevereiro | 66 | 8 | 74 |
| 2019 Janeiro | 60 | 8 | 68 |
| 2018 Dezembro | 78 | 12 | 90 |
| 2018 Novembro | 171 | 17 | 188 |
| 2018 Outubro | 572 | 14 | 586 |
| 2018 Setembro | 74 | 12 | 86 |
| 2018 Agosto | 46 | 12 | 58 |
| 2018 Julho | 43 | 7 | 50 |
| 2018 Junho | 60 | 5 | 65 |
| 2018 Maio | 62 | 14 | 76 |
| 2018 Abril | 136 | 8 | 144 |
| 2018 Maro | 53 | 10 | 63 |
| 2018 Fevereiro | 45 | 2 | 47 |
| 2018 Janeiro | 42 | 11 | 53 |
| 2017 Dezembro | 76 | 12 | 88 |
| 2017 Novembro | 40 | 8 | 48 |
| 2017 Outubro | 30 | 11 | 41 |
| 2017 Setembro | 43 | 11 | 54 |
| 2017 Agosto | 36 | 8 | 44 |
| 2017 Julho | 31 | 6 | 37 |
| 2017 Junho | 52 | 13 | 65 |
| 2017 Maio | 37 | 15 | 52 |
| 2017 Abril | 44 | 5 | 49 |
| 2017 Maro | 37 | 4 | 41 |
| 2017 Fevereiro | 36 | 5 | 41 |
| 2017 Janeiro | 41 | 5 | 46 |
| 2016 Dezembro | 23 | 12 | 35 |
| 2016 Novembro | 26 | 13 | 39 |
| 2016 Outubro | 17 | 6 | 23 |
| 2016 Setembro | 70 | 8 | 78 |
| 2016 Agosto | 190 | 0 | 190 |
| 2016 Julho | 23 | 2 | 25 |
| 2016 Junho | 11 | 4 | 15 |
| 2016 Maio | 6 | 6 | 12 |
| 2016 Abril | 46 | 5 | 51 |
| 2016 Maro | 56 | 18 | 74 |
| 2016 Fevereiro | 82 | 25 | 107 |
| 2016 Janeiro | 54 | 15 | 69 |
| 2015 Dezembro | 67 | 15 | 82 |
| 2015 Novembro | 59 | 17 | 76 |
| 2015 Outubro | 68 | 26 | 94 |
| 2015 Setembro | 64 | 24 | 88 |
| 2015 Agosto | 41 | 10 | 51 |
| 2015 Julho | 54 | 5 | 59 |
| 2015 Junho | 45 | 8 | 53 |
| 2015 Maio | 58 | 12 | 70 |
| 2015 Abril | 57 | 24 | 81 |
| 2015 Maro | 52 | 15 | 67 |
| 2015 Fevereiro | 47 | 12 | 59 |
| 2015 Janeiro | 36 | 18 | 54 |
| 2014 Dezembro | 55 | 21 | 76 |
| 2014 Novembro | 103 | 22 | 125 |
| 2014 Outubro | 123 | 105 | 228 |
Mostrar tudo
