Stroke Prevention in Atrial Fibrillation: Focus on Latin
America

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Abstract

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, with an estimated prevalence of 1-2% in North America and Europe. The increased prevalence of AF in Latin America is associated with an ageing general population, along with poor control of key risk factors, including hypertension. As a result, stroke prevalence and associated mortality have increased dramatically in the region. Therefore, the need for effective anticoagulation strategies in Latin America is clear. The aim of this review is to provide a contemporary overview of anticoagulants for stroke prevention.

The use of vitamin K antagonists (VKAs, eg, warfarin) and aspirin in the prevention of stroke in patients with AF in Latin America remains common, although around one fifth of all AF patients receive no anticoagulation. Warfarin use is complicated by a lack of access to effective monitoring services coupled with an unpredictable pharmacokinetic profile. The overuse of aspirin is associated with significant bleeding risks and reduced efficacy for stroke prevention in this patient group. The non-VKA oral anticoagulants (NOACbs) represent a potential means of overcoming many limitations associated with VKA and aspirin use, including a reduction in the need for monitoring and a reduced risk of hemorrhagic events.

The ultimate decision of which anticoagulant drug to utilize in AF patients depends on a multitude of factors. More research is needed to appreciate the impact of these factors in the Latin American population and thereby reduce the burden of AF-associated stroke in this region.

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Most cited references 166

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Risk factors for stroke and efficacy of antithrombotic therapy in atrial fibrillation. Analysis of pooled data from five randomized controlled trials.

S Connolly, MD Ezekowitz, RG Hart … (1994)

Atrial fibrillation is associated with an increased risk of ischemic stroke. Data on individual patients were pooled from five recently completed randomized trials comparing warfarin (all studies) or aspirin (the Atrial Fibrillation, Aspirin, Anticoagulation Study and the Stroke Prevention in Atrial Fibrillation Study) with control in patients with atrial fibrillation. The purpose of the analysis was to (1) identify patient features predictive of a high or low risk of stroke, (2) assess the efficacy of antithrombotic therapy in major patient subgroups (eg, women), and (3) obtain the most precise estimate of the efficacy and risks of antithrombotic therapy in atrial fibrillation. For the warfarin-control comparison there were 1889 patient-years receiving warfarin and 1802 in the control group. For the aspirin-placebo comparison there were 1132 patient-years receiving aspirin and 1133 receiving placebo. The daily dose of aspirin was 75 mg in the Atrial Fibrillation, Aspirin, Anticoagulation Study and 325 mg in the Stroke Prevention in Atrial Fibrillation Study. To monitor warfarin dosage, three studies used prothrombin time ratios and two used international normalized ratios. The lowest target intensity was a prothrombin time ratio of 1.2 to 1.5 and the highest target intensity was an international normalized ratio of 2.8 to 4.2. The primary end points were ischemic stroke and major hemorrhage, as assessed by each study. At the time of randomization the mean age was 69 years and the mean blood pressure was 142/82 mm Hg. Forty-six percent of the patients had a history of hypertension, 6% had a previous transient ischemic attack or stroke, and 14% had diabetes. Risk factors that predicted stroke on multivariate analyses in control patients were increasing age, history of hypertension, previous transient ischemic attack or stroke, and diabetes. Patients younger than 65 years who had none of the other predictive factors (15% of all patients) had an annual rate of stroke of 1.0%, 95% confidence interval (CI) 0.3% to 3.0%. The annual rate of stroke was 4.5% for the control group and 1.4% for the warfarin group (risk reduction, 68%; 95% CI, 50% to 79%). The efficacy of warfarin was consistent across all studies and subgroups of patients. In women, warfarin decreased the risk of stroke by 84% (95% CI, 55% to 95%) compared with 60% (95% CI, 35% to 76%) in men. The efficacy of aspirin was not as consistent. The risk reduction with 75 mg of aspirin in the Atrial Fibrillation, Aspirin, Anticoagulation Study was 18% (95% CI, 60% to 58%), and with 325 mg of aspirin in the Stroke Prevention in Atrial Fibrillation Study the risk reduction was 44% (95% CI, 7% to 66%). When both studies were combined the risk reduction was 36% (95% CI, 4% to 57%). The annual rate of major hemorrhage (intracranial bleeding or a bleed requiring hospitalization or 2 units of blood) was 1.0% for the control group, 1.0% for the aspirin group, and 1.3% for the warfarin group. In these five randomized trials warfarin consistently decreased the risk of stroke in patients with atrial fibrillation (a 68% reduction in risk) with virtually no increase in the frequency of major bleeding. Patients with atrial fibrillation younger than 65 years without a history of hypertension, previous stroke or transient ischemic attack, or diabetes were at very low risk of stroke even when not treated. The efficacy of aspirin was less consistent. Further studies are needed to clarify the role of aspirin in atrial fibrillation.

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The global burden of atrial fibrillation and stroke: a systematic review of the epidemiology of atrial fibrillation in regions outside North America and Europe.

Gregory Lip, Carolyn M Brechin, Deirdre Lane (2012)

Although atrial fibrillation (AF) is accepted as the most common sustained cardiac arrhythmia, most published epidemiologic studies focus on predominantly white populations in North America or Europe, and information on AF in nonwhite populations is scarce. The objective of this study was to undertake a systematic review of the published literature on the epidemiology of AF in other regions. Systematic literature searches (MEDLINE; 1990-2010) identified epidemiologic studies reporting on the prevalence or incidence of AF, stroke in AF, risk factors for AF, or the use of antithrombotic therapy in countries outside North America and Europe. This report presents a descriptive analysis of the data; no meta-analysis was planned. Many of the 38 articles identified were from the Far East, although Australia, New Zealand, the Middle East, and South America were also represented. The reported prevalence of AF varied among countries, with different ranges in community- and hospital-based studies (0.1%-4% and 2.8%-14%, respectively). The use of anticoagulant therapy varied widely among countries and studies, as did the reported prevalence of stroke in patients with AF (2.8%-24.2%). High-quality epidemiologic studies are clearly required to improve understanding of the worldwide burden of AF and stroke in AF. Major improvements in the provision of thromboprophylaxis are also needed in many countries, given the high proportion of untreated patients who are, hence, at risk of stroke.

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Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial.

John Amerena, Adriana R. Lopes, Ziad Hijazi … (2012)

Atrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function. Baseline glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cockcroft-Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of >80 mL/min, 7587 (42%) between >50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft-Gault {hazard ratio (HR) 0.50 [95% confidence interval (CI) 0.38-0.66], interaction P = 0.005} or CKD-EPI equations [HR 0.48 (95% CI 0.37-0.64), interaction P = 0.003]. In patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.

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Author and article information

Journal

Journal ID (nlm-ta): Arq Bras Cardiol

Journal ID (iso-abbrev): Arq. Bras. Cardiol

Journal ID (publisher-id): abc

Title: Arquivos Brasileiros de Cardiologia

Publisher: Sociedade Brasileira de Cardiologia - SBC

ISSN (Print): 0066-782X

ISSN (Electronic): 1678-4170

Publication date (Print and electronic): December 2016

Publication date (Print): December 2016

Volume: 107

Issue: 6

Pages: 576-589

Affiliations

[1 ]Hospital Sírio Libanês, São Paulo, SP - Brazil

[2 ]Divisão de Neurologia - Instituto do Cérebro do Rio Grande do Sul - PUCRS, Porto Alegre, RS - Brazil

[3 ] University of Birmingham Institute of Cardiovascular Sciences - City Hospital - Birmingham, United Kingdom

[4 ] Aalborg Thrombosis Research Unit - Department of Clinical Medicine - Faculty of Health - Aalborg University, Aalborg, Denmark

Author notes

Mailing Address: Ayrton R. Massaro, Hospital Sirio Libanês. Rua Dona Adma Jafet, 115. Postal Code 01308-050, Bela Vista, SP - Brazil. E-mail: ayrton.massaro@ 123456gmail.com

Article

DOI: 10.5935/abc.20160116

PMC ID: 5210462

PubMed ID: 27533256

SO-VID: 587d258d-717b-43d9-adb2-3de2767d6534

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.