Credit: CDC
The US Food and Drug Administration (FDA) is evaluating trial data suggesting that 30 months of dual antiplatelet therapy (DAPT), compared to 12 months of the therapy, can increase the overall risk of death among patients who have a drug-eluting coronary stent.
The trial, which was published in NEJM, also indicates that longer-term DAPT can decrease the risk of stent thrombosis and major cardiovascular and cerebrovascular events.
For this trial, researchers compared 12 months and 30 months of DAPT—aspirin plus either clopidogrel or prasugrel—in 9961 patients who had a drug-eluting stent. The team also enrolled patients with bare-metal stents, but those patients were not included in this publication.
All 9961 patients received aspirin and clopidogrel/prasugrel for 12 months. Then, they were randomized to continue DAPT for another 18 months or to receive aspirin and placebo during that period.
In the 30-month group, 65.2% of patients received clopidogrel, and 34.8% received prasugrel. In the 12-month group, 65.4% of patients received clopidogrel, and 34.6% received prasugrel.
The investigators followed all patients for 33 months. At that point, 4732 patients in the 30-month group and 4658 patients in the 12-month group were evaluable.
The researchers observed a significant reduction in stent thrombosis for patients who received DAPT for 30 months compared to 12 months—0.4% vs 1.4% (hazard ratio [HR]=0.29, P<0.001).
Patients who received DAPT for 30 months also saw a reduction in major cardiovascular and cerebrovascular events, a combined endpoint of all-cause death, myocardial infarction, and stroke. The rate was 4.3% for the 30-month group and 5.9% for the 12-month group (HR 0.71, P<0.001).
The reduction in the risk of major cardiovascular and cerebrovascular events was driven by a decrease in the rate of non-fatal myocardial infarction. There were no differences in the rates of cardiovascular death or stroke.
The investigators also found that the overall death rate was higher among patients receiving DAPT for a longer period. The rate was 2.0% in the 30-month group and 1.5% in the 12-month group (HR=1.36, P=0.05).
The researchers said this can be explained by an increase in non-cardiovascular deaths (1% vs 0.5%, HR 2.2, P=0.002). The most frequent causes of non-cardiovascular death were cancer (34 deaths vs 17 deaths) and trauma (8 deaths vs 2 deaths) for 30 months and 12 months of DAPT, respectively.
The increase in overall mortality was present in clopidogrel-treated patients (2.2% vs 1.5%, respectively) but not prasugrel-treated patients (1.6% vs 1.6%). The FDA noted that other large clopidogrel trials have not shown an increase in the risk of non-cardiovascular death.
The FDA said it plans to evaluate the results from this trial and other relevant data, then announce its conclusions and recommendations.
For now, the agency said healthcare professionals should not change the way they administer DAPT. And patients should not stop taking these drugs, as this may result in an increased risk of heart attacks, thrombosis, strokes, and other major cardiovascular problems.
Healthcare professionals and patients can report adverse events or side effects related to the aforementioned drugs to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program.
