When to Use Antiplatelets vs Anticoagulants
Use antiplatelets (aspirin or clopidogrel) for arterial thrombosis prevention in atherosclerotic disease; use anticoagulants (warfarin, DOACs) for venous thromboembolism and cardioembolic stroke prevention, particularly in atrial fibrillation. 1
Core Decision Framework
Antiplatelets Are Indicated For:
Coronary artery disease (stable or acute): Aspirin 75-100 mg daily or clopidogrel 75 mg daily reduces myocardial infarction, stroke, and cardiovascular death by approximately 25% 1
Peripheral arterial disease (symptomatic): Single antiplatelet therapy with aspirin 75-160 mg daily or clopidogrel 75 mg daily is recommended for MACE reduction 1
Post-stroke/TIA: Antiplatelet monotherapy prevents recurrent ischemic events in atherothrombotic stroke 1, 2
After percutaneous coronary intervention: Dual antiplatelet therapy (aspirin + clopidogrel) for 1-12 months depending on stent type and clinical presentation 1
Anticoagulants Are Indicated For:
Atrial fibrillation with elevated stroke risk: DOACs (apixaban, rivaroxaban, dabigatran) or warfarin prevent cardioembolic stroke, with DOACs preferred over warfarin due to lower bleeding risk 1, 3
Venous thromboembolism: Anticoagulation is the primary treatment for deep vein thrombosis and pulmonary embolism 1
Mechanical heart valves: Warfarin is required for thrombosis prevention 1
Left ventricular thrombus: Anticoagulation prevents systemic embolization 1
High-Risk Scenarios Requiring Combined Therapy
Acute Coronary Syndrome + Atrial Fibrillation:
Triple therapy (OAC + aspirin ≤100 mg + clopidogrel) should be limited to 1 month maximum, then transition to dual therapy (OAC + clopidogrel) up to 12 months, followed by OAC monotherapy 1, 3
For patients with high bleeding risk (HAS-BLED ≥3), consider dual therapy (OAC + clopidogrel) from the outset, omitting aspirin entirely 1
DOACs at the lowest stroke-prevention dose are preferred over warfarin when combined with antiplatelets 1, 3
Never use prasugrel or ticagrelor as part of triple therapy—clopidogrel is the only acceptable P2Y12 inhibitor due to lower bleeding risk 1, 3
Proton pump inhibitor prophylaxis is mandatory for all patients on combined anticoagulant and antiplatelet therapy 3
Peripheral Arterial Disease with High Ischemic Risk:
Combination rivaroxaban 2.5 mg twice daily + aspirin 100 mg daily should be considered for patients with PAD at high ischemic risk and non-high bleeding risk 1, 4
High ischemic risk includes: previous amputation, chronic limb-threatening ischemia, or recent lower extremity revascularization 1
This combination reduces major thrombotic vascular events (MI, stroke, cardiovascular death, acute limb ischemia) by 26-28% compared to aspirin alone 4
In VOYAGER trial, this strategy resulted in 181 fewer primary outcome events per 10,000 patient-years, with only 29 additional TIMI major bleeding events 4
Critical Distinctions in Mechanism
Antiplatelets target arterial (white) thrombi formed under high shear stress conditions where platelet aggregation predominates—this is the pathophysiology of atherosclerotic plaque rupture 1, 2
Anticoagulants target venous (red) thrombi formed under low shear stress where the coagulation cascade and fibrin generation predominate—this is the pathophysiology of atrial fibrillation and venous stasis 1
Common Pitfalls to Avoid
Never use dual antiplatelet therapy alone in patients with atrial fibrillation and CHA2DS2-VASc ≥2—this inadequately addresses stroke risk, which requires anticoagulation 3
Never continue triple therapy beyond 1 month in most patients—bleeding risk substantially outweighs marginal thrombotic benefit after this period 1, 3
Never add clopidogrel to aspirin for routine management of bleeding complications—switch to clopidogrel monotherapy instead if aspirin must be discontinued 5
Never use anticoagulant monotherapy for coronary artery disease without another indication—antiplatelets are superior for atherothrombotic prevention 1
In patients requiring long-term anticoagulation for atrial fibrillation who also have stable PAD, use OAC monotherapy rather than adding antiplatelet therapy unless there is recent revascularization 1
Duration of Dual Antiplatelet Therapy Post-PCI
For bare metal stents or drug-eluting stents in stable CAD: 1 month of dual antiplatelet therapy, then single antiplatelet therapy 1
For drug-eluting stents in acute coronary syndrome: 12 months of dual antiplatelet therapy (aspirin 75-100 mg + clopidogrel 75 mg), then single antiplatelet therapy 1