Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects. part 16
The results obtained in aspirin trials that have recruited high-risk men and women (ie, the Thrombosis Prevention Trial, Hypertension Optimal Treatment [HOT] trial, and the Primary Prevention Project) [Fig 1] clearly demonstrate that proper management of modifiable risk factors by current multifactorial strategies can reduce the actual risk of experiencing a major vascular event to a level at which the additional benefit of aspirin does not clearly outweigh the risk of major bleeding complications (Fig 1). Additional data assessing the benefit/risk ratio of long-term aspirin prophylaxis in apparently healthy persons are currently being collected by the Women’s Health Study, an ongoing trial of low-dose aspirin therapy (100 mg every other day) among 40,000 US female health-care professionals.
While the clinical issues related to policy recommendations concerning aspirin in the primary prevention of cardiovascular disease are discussed in detail elsewhere in this supplement, the results of the studies reviewed above do not justify the use of a daily dose of aspirin of > 75 to 100 mg when primary prevention with aspirin is considered in the setting of varying individual patient values and preferences.
Аtrial fibrillation
Moderate-dose warfarin alone (international normalized ratio [INR], 2.0 to 3.0) is very effective in reducing the risk of stroke in patients with nonvalvular atrial fibrillation. The effectiveness of aspirin therapy in doses between 75 and 325 mg has been compared with therapy with warfarin and placebo in three randomized trials of patients with nonvalvular atrial fibrillation. In one study, therapy with aspirin was significantly more effective than that with placebo, whereas in the other two studies there was a nonsignificant trend in favor of aspirin therapy. A pooled analysis of the three studies shows a reduction in relative risk (RR) of about 25% (range, 14 to 44%), which is in favor of therapy with aspirin over that with placebo. Aspirin therapy was significantly less effective than that with warfarin in two stud-ies on an intention-to-treat analysis, and in the third study with an efficacy analysis. On pooled analysis, warfarin therapy was significantly more effective than aspirin, with a 47% RR reduction (range, 28 to 61%; p < 0.01). Moreover, adjusted-dose warfarin therapy (INR, 2.0 to 3.0) was more effective than fixed low-dose warfarin therapy (INR, 1.2 to 1.5) and aspirin therapy (325 mg/d) in high-risk patients with atrial fibrillation. Thus, therapy with aspirin appears to be effective in preventing stroke in patients with atrial fibrillation but is substantially less effective than therapy with warfarin. However, aspirin is less expensive, safer, and more convenient than warfarin, and may be considered for patients who are unable to receive anticoagulation therapy or those with lone atrial fibrillation who have a low risk of stroke.