medwireNews: The long-term use of clopidogrel monotherapy after stopping dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI) may result in fewer cardiovascular events compared with aspirin monotherapy, with no significant difference in the risk for major bleeding, show 5-year findings from the STOPDAPT-2 trial.
Writing in the Journal of the American College of Cardiology, Takeshi Kimura (Hirakata Kohsai Hospital, Osaka, Japan) and colleagues say: “The risk reduction in cardiovascular events was mainly driven by the statistically significant 39% risk reduction in myocardial infarction.”
They add: “Moreover, stent thrombosis and ischemic stroke were numerically reduced in the clopidogrel group vs the aspirin group,” with corresponding rates of 0.28% versus 0.50% and 1.52% versus 2.08%, which they note is “consistent with previous studies.”
For the trial, 3045 patients who had undergone PCI with a cobalt–chromium everolimus-eluting stent were randomly assigned to receive monotherapy with the P2Y12 receptor antagonist clopidogrel after 1 month of DAPT or aspirin monotherapy after 12 months of DAPT.
The mean age of the patients was 68.6 years, 22.3% were women, and 38.3% had acute coronary syndrome (ACS).
At 5 years, 3005 patients were available for the intention-to-treat analysis – 1498 in the clopidogrel treatment group and 1507 in the aspirin treatment group.
The primary endpoint was net adverse clinical events, defined as a composite of cardiovascular outcomes (death from cardiovascular causes, myocardial infarction, stent thrombosis, or stroke) and major bleeding (meeting Thrombolysis in Myocardial Infarction criteria for major or minor bleeding). The secondary outcomes included the cardiovascular and bleeding components of the primary endpoint considered separately.
The primary endpoint occurred in 11.75% of patients in the clopidogrel group over the 5-year study period, compared with 13.5% of those in the aspirin group, giving a nonsignificant hazard ratio (HR) of 0.85. This meant clopidogrel was noninferior but not superior to the aspirin group for this composite primary endpoint.
Superiority with clopidogrel treatment over aspirin was seen when only cardiovascular outcomes were considered, occurring in 8.61% versus 11.05% of patients, and a significant HR of 0.77. By contrast, clopidogrel was not superior to aspirin at reducing major bleeding, with similar rates of 4.44% and 4.92%, respectively, and a nonsignificant HR of 0.89.
In the 1-year landmark analysis, clopidogrel showed numerical superiority over aspirin for cardiovascular events (6.79 vs 8.68%; HR: 0.77), although the difference was not statistically significant.
The researchers comment that "[t]he cumulative 5-year incidences of esophagogastroduodenoscopy and newly diagnosed cancer were not different between the 2 groups,” adding that “the mortality rate was also similar,” at 8.48% in the clopidogrel group versus 9.19% in the aspirin group, and there was “no signal suggesting an increase in noncardiovascular death.”
They conclude: “Clopidogrel might be an attractive alternative to aspirin with a borderline ischemic benefit beyond 1 year after PCI.”
In a related editorial, Anne Bellemain-Appaix (Antibes Hospital, France) and Gilles Montalscot (Pitié-Salpêtrière Hospital, Paris, France) comment: “This important study confirms that ischemic protection post-PCI is better ensured by clopidogrel than aspirin from 1 month to 5 years.”
They point out that de-escalation of DAPT therapy immediately after PCI “needs to be carefully thought out,” as it can be harmful “particularly in patients with ACS.”
The editorialists conclude: “DAPT should remain the standard of care for 1 month after coronary stent implantation. Beyond 1 month, possibly 3 months in ACS or high ischemic risk patients, de-escalation strategies to a P2Y12 inhibitor alone may become the new standard of care among select, if not most, patients.”
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group.
J Am Coll Cardiol 2024; 83: 17–31
J Am Coll Cardiol 2024; 83: 32–34