Antiplatelet Therapy for Preventing Stroke in Patients With Nonvalvular Atrial Fibrillation and No Previous History of Stroke or Transient Ischemic Attacks
Antiplatelet agents such as aspirin are modestly efficacious for preventing serious vascular events in patients with atrial fibrillation (AF) who are not treated with more efficacious oral anticoagulants.
Nonvalvular AF carries an increased risk of stroke. Antiplatelet therapy (APT) is proven effective for stroke prevention in most patients at high-risk for vascular events, but its value for primary stroke prevention in patients with nonvalvular AF merits separate consideration because of the suspected cardioembolic mechanism of most strokes in AF patients.
The goal of this review is to assess the efficacy and safety of long-term APT for primary prevention of stroke in patients with chronic nonvalvular AF.
We searched the Cochrane Stroke Group Trials Register (August 2004). In addition, we searched the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to June 2004), and the reference lists of recent review articles. We also contacted experts working in the field to identify unpublished and ongoing trials.
Data Collection and Analysis
Randomized trials comparing long-term APT with placebo or control in patients with nonvalvular AF and no history of transient ischemic attack (TIA) or stroke were independently selected and analyzed by 2 authors, extracting the data for each outcome. A sensitivity analysis included 1 additional randomized trial1 involving primary prevention with aspirin plus very low-dose warfarin versus control. An additional randomized trial, the Japanese Atrial Fibrillation Stroke Trial, has been completed, but results have not been published.
Three trials tested aspirin in dosages ranging from 75 mg to 325 mg per day and 125 mg every other day to placebo (in 2 trials LASAF2 and AFASAK3) or control (in 1 trial SPAF I4) in 1965 AF patients without previous stroke or TIA. The mean duration of follow-up averaged 1.3 years per participant. Aspirin was associated with nonsignificant lower risks of all stroke (odds ratio [OR], 0.70; 95% CI, 0.47 to 1.07), ischemic stroke (OR, 0.70; 95% CI, 0.46 to 1.07), all disabling or fatal stroke (OR, 0.86; 95% CI, 0.50 to 1.49) and all-cause death (OR, 0.75; 95% CI, 0.54 to 1.04). The combination of stroke, myocardial infarction, or vascular death was significantly reduced (OR, 0.71; 95% CI, 0.51 to 0.97; Figure). No significant increase in intracranial hemorrhage or major extra cranial hemorrhage was observed, but numbers were small and CIs wide.
Aspirin reduces stroke and major vascular events in patients with nonvalvular AF similar to its effect in other high-risk patients (ie, by ≈25%). For primary prevention among AF patients with an average stroke rate of 4% per year, ≈10 strokes would likely be prevented yearly for every 1000 AF patients given aspirin.
Implications for Practice
The benefits of APT are modest compared with adjusted-dose warfarin, but APT is relatively safe, easy to take, and therefore an important treatment option for many AF patients. Anticoagulation with warfarin and related drugs offers more protection against stroke (nearly two-thirds reduction), but anticoagulant drugs can cause severe bleeding and require careful regulation with regular blood tests. The choice of APT versus anticoagulants should be individualized based on the patient’s inherent risk of stroke,5 ability to tolerate anticoagulation without bleeding, access to adequate anticoagulation monitoring, and patient preferences.
Implications for Research
More randomized data about the efficacy of nonaspirin APT regimens (including dipyridamole, clopidogrel, and indobufen, alone and combined with aspirin) might expand the use of APT in AF patients.
Section Editor: Graeme J. Hankey, MD, FRCP
- Received September 6, 2005.
- Accepted October 11, 2005.
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