Time to Drop Aspirin for Long-term Antiplatelet Therapy?

Volume 28, Issue 1

Aspirin is a drug under siege. Recent evidence has called into question whether this drug has any value in the primary prevention of cardiovascular disease, including in high-risk patients like those with diabetes. Similarly, in patients who require both antiplatelet and anticoagulant therapy (ie triple therapy), recent evidence supports dropping aspirin in favor a dual drug regimen of a P2Y12 receptor antagonist and a direct-acting oral anticoagulant. 

For long-term secondary prevention, however, aspirin is still king. Most guidelines still recommend long-term therapy with aspirin after patients have finished dual antiplatelet therapy (DAPT) for prevention of recurrent major adverse cardiovascular events. 

However, the use of aspirin for this purpose is largely empiric, and recent interest has developed in exploring the value of long-term monotherapy with a P2Y12 receptor antagonist over aspirin. In this issue of Talking Therapeutics, we explore a recent study that evaluated long-term outcomes for patients with a drug-eluting stent who were randomized to receive either aspirin or a P2Y12 receptor blocker. 

Point 1: Score One for P2Y12 Receptors

This new paper involved patients who were randomized after drug-eluting stent placement to a long-term course (around 5.8 years follow-up) of either clopidogrel or aspirin monotherapy. The primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, readmission due to acute coronary syndrome (ACS), and major bleeding. 

The primary endpoint occurred significantly less with clopidogrel vs aspirin (12.8% vs 16.9%, P < .001). This outcome was driven largely by lower rates of bleeding, readmission for ACS, and ischemic stroke. 

Point 2: Evidence Is Growing

This paper has some caveats, mostly that it was conducted entirely with an Asian patient population. Two other trials, TWILIGHT and STOPDAPT-2, suggested P2Y12 monotherapy could be continued after a short course of DAPT in patients undergoing percutaneous coronary intervention for stable ischemic heart disease and ACS. Further, data exist showing that long-term P2Y12 inhibitor monotherapy may provide comparable outcomes to long-term DAPT.

Taken together, this evidence suggests aspirin could lose another long-standing indication for the prevention of cardiovascular diseases.