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Atrial fibrillation (AF) is the most common cardiac arrhythmia in the elderly, affecting 1 in 20 adults over the age of 70 years. Stroke is a major yet highly preventable complication of AF, and the strokes related to AF often are disabling and fatal. Warfarin is the treatment of choice in high-risk patients with AF, and its superior efficacy over aspirin for preventing stroke in these patients is widely recognized. However, several eligible patients with AF are not being treated with warfarin or are being treated inadequately, largely because of concerns regarding the attendant strict monitoring, drug interactions, and risk of major bleeding. As such, alternative antithrombotic therapies that can rival or exceed the efficacy of warfarin, yet compare favorably with its administration and side effect profile, are being sought. One such strategy, the use of a combination antiplatelet regimen, for stroke prevention in high-risk patients with nonvalvular AF was investigated recently in two clinical trials. This article reviews the role of combination antiplatelet regimens in stroke prevention for patients with AF. Other therapies discussed include oral anticoagulation, single antiplatelet therapies, oral anticoagulation plus antiplatelet treatment, direct thrombin inhibitors, and factor Xa inhibitors.
Atrial fibrillation (AF) is characterized by disordered electrical activity in the atria that causes an irregular and often rapid contraction of the ventricles . AF may limit itself, recur (paroxysmal), or be persistent (lasting more than 7 days), and its overall prevalence increases with age, from 0.7% in persons aged 55 to 59 years to 18% in those 85 years and older . The major complication of AF is systemic embolism (accounting for ~50% of all cardiogenic emboli), mostly to the cerebral vascular bed, the latter of which manifests as strokes. After adjustment for other vascular risk factors, AF alone is associated with a three-to fourfold increased risk of stroke, and more than 75,000 cases of AF-related stroke are believed to occur each year in the United States . These strokes generally are larger, more disabling, and more likely to be fatal than strokes of other causes.
Antithrombotic therapy is the cornerstone of stroke prevention among AF patients, and the incidence of ischemic stroke among patients with AF not treated with antithrombotic agents averages 4% to 5% per year, and may be greater than 13% per year in high-risk patients . Oral anticoagulation, which generally involves the use of warfarin, currently is the treatment of choice for mitigating stroke risk in AF patients, but its use is limited by a narrow therapeutic index that demands strict monitoring, several drug and dietary interactions, a lack of firm caregiver commitment to ensure compliance with treatment and follow-up visits, and the risk of major bleeding, including hemorrhagic stroke . Practitioners also have concerns about physical immobility from age-related health problems leading to falls and hemorrhagic complications, and whether participants in clinical trials, who generally are followed up more closely to ensure adherence to the study protocol, are representative of patients seen in “real-world” practice, who may not necessarily be compliant with management protocols.
All the aforementioned factors have led to suboptimal warfarin use in clinical practice, with as many as 50% of eligible AF patients not receiving it, or up to three quarters not being treated adequately. As a result, various alternative antithrombotic therapies have, and continue to be, actively investigated for stroke prevention in patients with AF. One such regimen is combination antiplatelet therapy. This review article discusses up-to-date evidence-based antithrombotic treatment for stroke prevention in AF patients, with a major emphasis on the role of combination antiplatelet therapy.
Dr. Ovbiagele received support from the University of California, Los Angeles, Resource Centers for Minority Aging Research, Center for Health Improvement of Minority Elderly (RCMAR/CHIME) under National Institutes of Health/National Institute on Aging grant P30-AG021684.
Disclosure No potential conflicts of interest relevant to this article were reported.
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