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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Atrial fibrillation &#40;AF&#41; is the most prevalent chronic arrhythmia&#46; It can cause significant hemodynamic alterations&#44; but its prognosis is mainly affected by associated thromboembolic phenomena&#44; which can have serious consequences in terms of morbidity and mortality&#46; Non-valvular AF increases the risk of ischemic stroke four- to five-fold in all age-groups&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a> Stroke is the leading cause of cardiovascular mortality and disability in Portugal&#44; hence the importance of preventive measures&#44; including prevention of thromboembolism in AF&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The pathogenesis of AF is complex&#44; involving various factors such as atrial blood stasis&#44; endothelial injury and dysfunction&#44; inflammation and systemic or local hypercoagulability&#46; Oral anticoagulation &#40;OAC&#41; with vitamin K antagonists &#40;VKAs&#41; is effective for stroke prevention in patients with non-valvular AF&#58; a meta-analysis of six studies showed a risk reduction of 64&#37; compared to placebo&#44; the number needed to treat in one year to prevent one stroke being 37 patients in primary prevention or 12 patients in secondary prevention&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a> OAC is also associated with a significant reduction &#40;26&#37;&#41; in overall mortality compared to placebo&#46; These findings support the recommendation in the European Society of Cardiology&#39;s guidelines that all patients with AF should be prescribed OAC therapy&#44; except those with low thromboembolic risk or isolated AF&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">For a variety of reasons&#44; many patients with non-valvular AF who are eligible for OAC are not anticoagulated&#46; One of the main limitations of VKAs is the increased risk of intracranial hemorrhage &#40;ICH&#41;&#44; which is responsible for 90&#37; of deaths from bleeding in AF patients treated with VKAs&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> The brain is a vital organ&#44; highly vascularized and vulnerable to mechanical injury&#44; but the cerebral microcirculation has a series of structural and functional properties that protect it against bleeding&#44; including strong junctions between endothelial cells&#44; low expression of antithrombotic molecules&#44; and high expression of tissue factor &#40;factor III&#41;&#44; which triggers coagulation when it binds to circulating factor VIIa&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a> The synthesis of factor VII requires vitamin K&#44; which explains the increased risk for ICH in patients taking VKAs&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Many patients anticoagulated with VKAs are not adequately controlled&#46; Observational studies have shown that the quality of control of the international normalized ratio &#40;INR&#41;&#44; as assessed by time in therapeutic range &#40;TTR&#41;&#44; is a strong predictor of mortality&#44; embolic events and bleeding complications in AF patients taking VKAs&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">6</span></a> INR must be closely monitored in order to optimize the effectiveness of VKA therapy&#46; With regard to safety&#44; the risk of ICH is lower the greater the TTR&#44; but it is always higher than in non-anticoagulated patients&#44; even when INR is well controlled&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The new oral anticoagulants &#40;NOACs&#41;&#44; direct factor Xa or thrombin inhibitors&#44; were developed in order to overcome the limitations of VKAs&#44; which are a challenge for both patients and their doctors&#46; In large-scale controlled trials&#44; dabigatran&#44; rivaroxaban&#44; apixaban and edoxaban were shown to be at least as effective as warfarin for prevention of stroke and systemic embolism in AF patients at moderate or high thromboembolic risk&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">8&#8211;11</span></a> The risk of ICH is significantly lower with any of the four NOACs compared to warfarin&#44; independently of INR control as assessed by TTR&#46; A meta-analysis of the RE-LY&#44; ROCKET AF&#44; ARISTOTLE and ENGAGE AF-TIMI trials&#44; with a total of 71<span class="elsevierStyleHsp" style=""></span>683 patients&#44; demonstrated that the NOACs reduce risk of stroke or systemic embolism by 19&#37;&#44; risk of ICH by 52&#37;&#44; risk of hemorrhagic stroke by 51&#37;&#44; and all-cause mortality by 10&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">12</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">When choosing a NOAC for a particular patient&#44; the physician cannot make an evidence-based decision&#44; since there have been no trials directly comparing two or more NOACs&#46; In the four published trials comparing individual NOACs with warfarin&#44; there are considerable differences in study design and population characteristics&#44; which affect thromboembolic event rates and bleeding complications&#44; as well as variations in INR&#46; There are also differences in definitions of endpoints&#44; warfarin dose adjustment methods&#44; and transition care&#46; All these factors seriously compromise the results obtained in indirect comparisons&#46; The European guidelines are accordingly clear as to the indications for preferring NOACs over VKAs&#44; but say nothing about choosing between them&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The cost-effectiveness of three NOACs &#40;dabigatran&#44; rivaroxaban and apixaban&#41; compared to warfarin in patients with AF has been demonstrated in the Portuguese context&#46;<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">13&#8211;15</span></a> The results of an indirect comparison between two of these drugs&#44; dabigatran and rivaroxaban&#44; are published in this issue of the <span class="elsevierStyleItalic">Journal</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a> Besides the problems with such comparisons&#44; as pointed out above&#44; there are two important factors that limit the authors&#8217; analysis&#46; Firstly&#44; they do not present the proportion of patients taking 110<span class="elsevierStyleHsp" style=""></span>mg &#40;the more common dose in Portugal&#41; or 150<span class="elsevierStyleHsp" style=""></span>mg of dabigatran&#59; this significantly affects the results obtained&#44; since the two dosages have different safety and efficacy profiles&#46; Secondly&#44; a 15<span class="elsevierStyleHsp" style=""></span>mg dose of rivaroxaban is not considered&#44; but this is frequently used in clinical practice and has a lower daily cost than either dosage of dabigatran&#46; Since the cost of the drug is an essential component of the economic evaluation model&#44; the inclusion of this dosage could change the conclusion that dabigatran is dominant&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A recent analysis of 100<span class="elsevierStyleHsp" style=""></span>913 patients in 21 controlled trials confirms that the clinical differences between the NOACs are modest and depend on the relative importance given to bleeding complications and ischemic events&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a> This analysis also found no significant differences between the NOACs in terms of medical costs&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">To summarize&#44; there is still great potential for further health gains by preventing stroke in non-valvular AF&#46; To achieve this&#44; measures need to be taken to improve the diagnosis of AF and to increase the number of patients treated among those eligible for OAC&#46; In general&#44; the NOACs present a favorable balance between efficacy and safety compared to warfarin&#44; and so a greater proportion of eligible patients can undergo OAC therapy&#46; In the absence of specific trials&#44; no NOAC should be considered superior to another on the basis of indirect comparisons&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">How much does the choice of new oral anticoagulant matter for reducing the burden of stroke in atrial fibrillation&#63; We cannot be sure&#44; but probably not very much&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">The author has received honoraria from the following companies&#58; Bayer&#44; Boehringer Ingelheim&#44; Bristol-Myers Squibb&#47;Pfizer&#44; and Daiichi Sankyo&#46;</p></span></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Aguiar C&#46; Quanto importa a escolha do anticoagulante oral direto para a redu&#231;&#227;o da carga de acidente vascular cerebral na fibrilha&#231;&#227;o auricular&#63;&#46; Rev Port Cardiol&#46; 2016&#59;35&#58;149&#8211;151&#46;</p>"
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