Why We Give Antiplatelet Therapy in Ischemic Heart Disease and Stroke
Antiplatelet therapy is given to patients with ischemic heart disease (IHD) and stroke because platelets play a central role in the thrombotic complications of atherosclerosis—disruption of atherosclerotic plaques triggers platelet aggregation and thrombus formation, which directly causes acute coronary syndromes, myocardial infarction, and ischemic stroke. 1
Mechanism of Action and Rationale
Platelets are the primary culprit in arterial thrombosis. When atherosclerotic plaques rupture or become unstable, platelets rapidly aggregate at the site, forming thrombi that occlude arteries supplying the heart or brain 1
Antiplatelet agents block this platelet aggregation cascade, preventing new clot formation and reducing the risk of recurrent ischemic events 2
In ischemic stroke specifically, most events result from sudden arterial blockage due to blood clots, making antiplatelet therapy a logical first-line intervention to prevent clot propagation and recurrence 2
Evidence-Based Benefits in Stroke Prevention
Acute Phase Management
For minor stroke or high-risk TIA, dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel initiated within 12-24 hours reduces recurrent stroke risk by 24% compared to aspirin alone (RR 0.76,95% CI 0.68-0.83), though at the cost of increased major bleeding (RR 2.22) 3, 4
The benefit is most pronounced in the first 21-30 days, after which DAPT should be discontinued to avoid excessive bleeding risk without additional benefit 5, 4
For moderate-to-severe stroke, aspirin monotherapy (160-300 mg) initiated within 24-48 hours reduces early recurrent stroke and improves long-term outcomes 4
Long-Term Secondary Prevention
Single antiplatelet therapy (SAPT) with clopidogrel 75 mg daily is the preferred agent for long-term secondary stroke prevention, with alternative options including aspirin plus extended-release dipyridamole or aspirin alone 4, 6
Continuing DAPT beyond 21-30 days for routine secondary prevention is explicitly not recommended (Class III recommendation) due to increased bleeding risk without additional benefit 5, 4
Evidence-Based Benefits in Ischemic Heart Disease
In acute coronary syndromes, clopidogrel combined with aspirin improves outcomes across the spectrum of IHD, from unstable angina to myocardial infarction 1
Antiplatelet therapy reduces the composite endpoint of cardiovascular death, nonfatal MI, and nonfatal stroke, with the benefit driven predominantly by MI reduction 7
The mechanism parallels stroke prevention: blocking platelet aggregation at sites of plaque disruption prevents coronary thrombosis and subsequent myocardial ischemia 1
Special Clinical Scenarios
Symptomatic Intracranial Stenosis
- DAPT with aspirin plus clopidogrel for 90 days is recommended, then transition to aspirin monotherapy, combined with systolic BP <140 mmHg and high-dose statin therapy 4
Cardioembolic Stroke
- Antiplatelet therapy is NOT appropriate for cardioembolic stroke with atrial fibrillation—oral anticoagulation is mandatory, with direct oral anticoagulants preferred over warfarin 5, 4
Embolic Stroke of Undetermined Source
- Antiplatelet therapy is recommended, not oral anticoagulation, following the same long-term regimen as noncardioembolic stroke 4
Critical Pitfalls to Avoid
Never continue DAPT indefinitely beyond the clinically recommended timeframe (21-30 days for most patients, 90 days for intracranial stenosis), as hemorrhagic complications increase substantially 5, 4
Avoid combining clopidogrel with omeprazole or esomeprazole, as these CYP2C19 inhibitors reduce clopidogrel's effectiveness 4
Do not use aspirin >325 mg daily long-term, as side effects increase without additional benefit 4
Premature discontinuation of antiplatelet therapy significantly increases the risk of subsequent cardiovascular events—ensure medication adherence at every visit 4, 7
In patients with prior TIA or stroke, prasugrel is contraindicated due to higher rates of intracranial hemorrhage (4.2% thrombotic stroke + 2.3% ICH vs 1.2% with clopidogrel) 7
Summary of Mechanism
The fundamental reason antiplatelet therapy works in both IHD and stroke is that both conditions share a common pathophysiology: atherosclerotic plaque disruption leading to platelet-mediated thrombosis. By inhibiting platelet aggregation through various mechanisms (aspirin blocks thromboxane A2, clopidogrel/ticagrelor block P2Y12 receptors), these agents prevent thrombus formation and propagation, thereby reducing recurrent ischemic events in both vascular territories 6, 1