Should a patient with a recent brain infarct (cerebral infarction) who is already on warfarin (anticoagulant) be started on dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor (e.g. clopidogrel)?

Should Dual Antiplatelet Therapy Be Added to Warfarin After Recent Brain Infarct?

No, do not add dual antiplatelet therapy to warfarin in a patient with recent brain infarct—there is clear evidence that combining anticoagulation with antiplatelet agents increases bleeding risk without reducing stroke or MI compared with anticoagulant therapy alone. 1

Core Principle: Anticoagulation Alone for Atrial Fibrillation

• For patients with atrial fibrillation (the presumed indication for warfarin) who experience an ischemic stroke, continue warfarin alone without adding antiplatelet agents. 1
• The American Heart Association/American Stroke Association explicitly states there is no evidence that combining anticoagulation with an antiplatelet agent reduces the risk of stroke or MI compared with anticoagulant therapy alone in AF patients. 1
• The combination clearly increases bleeding risk, including major hemorrhage. 1

What If the Patient Has Concurrent Coronary Disease?

This is the only scenario where combining therapies may be justified, but with strict time limitations:

Recent Acute Coronary Syndrome (ACS) with Stenting

• If the patient had PCI with stenting for ACS, use "double therapy" (warfarin plus a P2Y12 inhibitor like clopidogrel) rather than triple therapy. 1
• The 2019 ACC/AHA/HRS guidelines recommend double therapy with warfarin and clopidogrel is reasonable to reduce bleeding risk compared with triple therapy. 1
• Duration depends on stent type:
  • Bare metal stent: minimum 1 month, ideally up to 12 months 2
  • Drug-eluting stent: minimum 3-6 months depending on type 2
• If triple therapy is used (warfarin, aspirin, clopidogrel), transition to double therapy at 4-6 weeks. 1
• Lower the warfarin target INR to 2.0-2.5 when combining with antiplatelet agents. 2

Stable Coronary Artery Disease

• Do not add aspirin to warfarin for stable coronary disease. 1
• Adjusted-dose warfarin (INR 2-3) offers MI protection comparable to aspirin in AF patients, making aspirin addition unnecessary and harmful. 1

What If the Stroke Occurred Despite Therapeutic Warfarin?

• Do not intensify antithrombotic therapy by adding antiplatelet agents. 1
• No data indicate that adding an antiplatelet agent provides additional protection against future ischemic events in patients who stroke on therapeutic anticoagulation. 1
• Both increasing anticoagulation intensity and adding antiplatelet agents are associated with increased bleeding risk without proven benefit. 1

Critical Pitfalls to Avoid

• Never combine warfarin with dual antiplatelet therapy (aspirin plus clopidogrel) for stroke prevention alone—this dramatically increases bleeding risk without benefit. 1, 3
• The combination of clopidogrel and aspirin for secondary stroke prevention has failed to document significant clinical benefits and substantially increases bleeding risk. 3
• Do not extrapolate benefits of dual antiplatelet therapy from coronary disease to cerebrovascular disease—recent trials show lack of efficacy and increased hemorrhage in stroke patients. 3

The Evidence Base

The European Atrial Fibrillation Trial (EAFT) demonstrated superior efficacy of anticoagulation over aspirin for stroke prevention in AF patients with recent TIA or minor stroke. 1 Multiple guidelines consistently recommend against combining therapies unless there is a specific, time-limited cardiac indication like recent stenting. 1

The ACTIVE trial showed that even in AF patients, combining clopidogrel with aspirin was inferior to warfarin alone (RR 1.44, P=0.0003), and when combined with warfarin, increased major bleeding without reducing thrombotic events. 1

Monitoring If Combination Therapy Is Necessary

If you must use combination therapy for a cardiac indication:

• Check INR weekly initially, then every 2-4 weeks once stable during the first 3 months. 2
• Monitor for gastrointestinal bleeding, intracranial hemorrhage, and other major bleeding at each encounter. 2
• Use low-dose aspirin (75-81 mg) specifically when combining agents to minimize bleeding risk. 2