Clopidogrel monotherapy was found to be more effective than aspirin monotherapy in lowering risk of major adverse cardiac and cerebrovascular events among patients at high risk of recurrent ischemic events who completed a standard duration of dual antiplatelet therapy (DAPT) following PCI, according to new research presented during a Late-Breaking Clinical Trial session at ACC.25 in Chicago and simultaneously published in The Lancet.

Between August 2020 and July 2023, in an open-label trial, 5,506 patients at 26 sites across South Korea (median age 65.0 years, 18.2% women) who underwent PCI were randomized 1:1 to either clopidogrel monotherapy 75 mg once daily (n=2,752) or aspirin monotherapy 100 mg once daily (n=2,754) following DAPT. All patients had a prior myocardial infarction (MI), medication-treated diabetes or complex coronary artery lesions.

Results showed that, at a median of 2.3 years follow-up, the composite primary endpoint of all-cause death, MI or stroke, was reached in 92 (4.4%) patients taking clopidogrel and 128 (6.6%) of those taking aspirin, with an absolute risk reduction of 2.2%, yielding a 29% lower likelihood of a primary outcome event in the clopidogrel group (p=0.013). This was primarily attributable to a greater reduction in MI with clopidogrel than aspirin (1% vs. 2.2%), as well as all-cause death (2.4% vs. 4.0%). The benefit was also observed to be greater in patients without a previous MI.

There was no significant difference between the two groups in the rate of stroke (both 1.3%), major bleeding events (both 3.0%) or incidence of adverse events.

"In general, the more potent antiplatelet therapy increases bleeding risk, but in our study, clopidogrel reduced the ischemic endpoints compared to aspirin but without increased risk of bleeding, so it's a very ideal result," said senior author, Joo-Yong Hahn, MD.

Limitations of the study include its open-label design, lack of a diverse patient pool at the South Korean centers and low proportion of women. Further analyses are planned to assess whether subgroups with specific cardiovascular and metabolic conditions experienced any difference in the rate of adverse outcomes.

"The current study provides some, rather than strong, evidence on the superiority of clopidogrel over aspirin," write Hahn, et al., "but the clinically meaningful absolute risk reduction of 2.2 percentage points and favorable number needed to treat (45 patients) provided relevant clinical insights for the selection of single antiplatelet regimen in the long-term maintenance period after PCI."