CONDITIONS IN WHICH ADDING ASPIRIN TO WARFARIN IS FAVORABLE
Acute coronary syndromes
Drugs that inhibit platelet function are the mainstay of medical treatment for acute coronary syndromes. The American College of Cardiology/American Heart Association (ACC/AHA) guidelines recommend that aspirin be started in patients who have an acute myocardial infarction even if they have been receiving warfarin long-term and their INR is in the therapeutic range, especially if a percutaneous coronary intervention is anticipated.4
After percutaneous coronary intervention
In patients who have undergone percutaneous coronary intervention with stent implantation, dual antiplatelet therapy with aspirin and a thienopyridine—ie, clopidogrel (Plavix) or ticlopidine (Ticlid)—is superior to aspirin or warfarin alone in reducing the risk of stent thrombosis and major adverse cardiovascular events such as myocardial infarction or urgent revascularization.18,19 If patients have an indication for long-term anticoagulation, triple therapy with aspirin, warfarin, and clopidogrel or ticlopidine may be considered in order to reduce the likelihood of stent thrombosis.4,20,21 In such patients the INR should be maintained between 2.0 and 3.0 to reduce the risk of bleeding.
The duration of triple therapy is guided by the type of stent used. For bare metal stents, aspirin, clopidogrel or ticlopidine, and warfarin should be given for at least 1 month, after which clopidogrel or ticlopidine may be discontinued. If drug-eluting stents are used, the duration of clopidogrel or ticlopidine therapy should be extended to 1 year or more.4,22
Mechanical heart valves
In patients with mechanical heart valves, the combination of aspirin and warfarin has been shown to decrease the frequency of thromboembolism.23 Guidelines recommend adding aspirin (75 to 100 mg per day) to warfarin in all patients with mechanical valves, especially in patients who have had an embolus while on warfarin therapy or who have a history of cerebrovascular or peripheral vascular disease, a hypercoagulable state, or coronary artery disease.24
CONDITIONS IN WHICH WARFARIN ALONE MAY BE SUFFICIENT
At risk of coronary artery disease
Aspirin therapy is generally recommended as primary prevention for patients whose estimated risk of coronary events is 1.5% per year or higher.25 However, warfarin has also been shown to be effective in the primary prevention of coronary artery disease in men,26 and for patients already taking warfarin, the possible benefit of adding aspirin for primary prevention is outweighed by the increased risk of major bleeding.14 The Medical Research Council directly compared low-intensity warfarin therapy (mean INR 1.47), aspirin, and placebo in a two-by-two factorial study of primary prevention of ischemic heart disease in men.26 Warfarin was more effective than aspirin, and men who received warfarin plus aspirin or warfarin plus placebo had a rate of ischemic heart disease that was 21% lower than those who received aspirin plus placebo or double placebo, and their rate of all-cause mortality was 17% lower. Combining aspirin and warfarin for patients at risk of coronary disease led to a higher rate of major bleeding but no difference in cardiovascular events or all-cause mortality (odds ratio 0.98; 95% confidence interval 0.77–1.25).14
Stable coronary artery disease without mechanical heart valves or stents
Large randomized trials have found warfarin to be effective in secondary prevention of coronary artery disease.4–6 For most patients with stable coronary artery disease (ie, who have had no ischemic events or coronary interventions in the last 6 months) who need anticoagulation because of atrial fibrillation or venous thromboembolism, warfarin alone (target INR 2.0–3.0) should provide satisfactory antithrombotic prophylaxis against both cerebral and myocardial ischemic events.27 The addition of an antiplatelet agent is not required unless a patient has a coronary stent, a mechanical valve, or an excessive thrombotic risk.4,24,27
For patients receiving warfarin therapy, whether to add or continue aspirin to their treatment is a common clinical question. The risk of bleeding is greater with combination therapy than with warfarin alone. The cardiovascular benefit varies depending on the clinical situation:
- In patients who have had an acute coronary syndrome or who have a coronary stent or mechanical valve, combination therapy is usually recommended because the benefits outweigh the risks.
- In patients with stable coronary artery disease or those without coronary artery disease who are at risk of coronary events, the risks outweigh the benefits. Combination therapy is usually not indicated in these patients.