Following a percutaneous coronary intervention (PCI) and 1 year of dual antiplatelet therapy (DAPT), clopidogrel is a better long-term monotherapy than aspirin, according to a real-world study that stratified patients by cardiovascular and bleeding risk.

“To provide the best long-term protection for patients, clopidogrel needs to be considered over aspirin,” according to the lead author Hao-Yu Wang, MD, PhD, who has appointments at Fuwai Hospital, the National Center for Cardiovascular Diseases, and Peking Union Medical College, all in Beijing, China.

In a single-center cohort created 6 years ago, about one third of the 5664 patients were prescribed clopidogrel, while the rest received aspirin, reflecting national trends of antiplatelet maintenance following PCI and DAPT in China, Wang said.

Clopidogrel Reduces Risk 38% vs Aspirin

After 2 years on antiplatelet monotherapy, the risk for a composite adverse outcome endpoint that included both cardiovascular and bleeding events was reduced by 38% (hazard ratio [HR], 0.62; P = .027) among those in the high bleeding risk subgroup treated with the P2Y12 inhibitor clopidogrel rather than low-dose aspirin.

The reduction of bleeding and cardiovascular events was even greater in the subgroup that had undergone complex PCI (HR, 0.45; P = .01). 

The reduction in adverse events favoring clopidogrel in both subgroups mainly involved the rate of cardiovascular events, said Wang, who presented these data at the Society for Cardiovascular Angiography and Intervention (SCAI) 2026.

Patients in the study were started on one of the two antiplatelet monotherapies following PCI and 12 months of DAPT. The cardiovascular events in the primary composite endpoint consisted of all-cause death, myocardial infarction, and stroke. Type 2, 3, or 5 bleeding on the Bleeding Academic Research Consortium scale represented the noncardiac events.

There were no major baseline differences between those started on clopidogrel or aspirin monotherapy overall or between those starting one of these therapies among the 1113 patients (19.7%) in the high bleeding risk subgroup or the 1953 patients (34.5%) in the complex PCI group.

High bleeding risk was defined by one major or two minor criteria of the Bleeding Academic Research Consortium. Complex PCI was defined by ≥ 3 lesions treated, bifurcation lesions treated with ≥ 2 stents and a total stent length > 60 mm, or chronic total occlusion.

The relative efficacy and safety of clopidogrel and aspirin were evaluated separately in those with no increased bleeding risk and noncomplex PCI, those with increased bleeding risk but no complex PCI, those with complex PCI but no increased bleeding risk, and those with both types of risk.

Clopidogrel Benefit Is Greater With Greater Risk

The 40% advantage for clopidogrel was marginally significant for those who had neither an increased bleeding risk nor a complex PCI (HR, 0.60; 95% CI, 0.37-0.97), but it reached 92% for those who had both (HR, 0.08; 95% CI, 0.01-0.59; P = .012).

There was a significant interaction effect (P = .028) of these risks in relation to clopidogrel, according to Wang.

When clopidogrel was compared with aspirin among those with a complex PCI but without a high bleeding risk, the difference did not reach statistical significance (HR, 0.71; 95% CI, 0.37-1.38). Among those with a high bleeding risk but a noncomplex PCI, there was a slight and nonsignificant disadvantage for clopidogrel (HR, 1.15; 95% CI, 0.60-2.22). 

STOPDAPT-2 Trials Produce Similar Message

These data were presented just 1 month after the final 5-year results of the open-label STOPDAPT-2 and STOPDAPT-2 ACS trials, combined as the 5997-patient STOPDAPT-2 Total Cohort, were published together. Although not addressing the same question, long-term clopidogrel monotherapy was again found to be superior to aspirin.

The two studies had the same design and endpoints. The difference was that STOPDAPT-2 ACS was restricted to patients who underwent PCI for an acute coronary syndrome, while STOPDAPT-2 enrolled all comers.

In both studies, patients undergoing PCI with everolimus-eluting stents were randomly assigned 1 month after DAPT to receive clopidogrel monotherapy indefinitely or to continue DAPT for the standard 12 months before switching to aspirin.

The primary composite endpoint at 5 years included cardiovascular events (cardiovascular death, myocardial infarction, stroke, or definite stent thrombosis) and bleeding (minor or major bleeding as defined by the Thrombosis in Myocardial Infarction criteria). 

For STOPDAPT-2 ACS, the advantage was significant for both the primary composite endpoint (HR, 0.75; P = .048) and the cardiovascular endpoint alone (HR, 0.74; P = .004) at 5 years. When all data were combined in the STOPDAPT-2 Total Cohort, the advantage did not reach statistical significance for the composite endpoint (HR, 0.86; P = .11) but was significant for the cardiovascular endpoint alone (HR, 0.70; P = .03). 

The take-home conclusion is that clopidogrel was superior to aspirin for cardiovascular outcomes beyond 1 year after PCI without increasing bleeding risk, according to the team of investigators led by Hirotoshi Watanabe, MD, senior researcher in the Department of Cardiology at Kyoto University Hospital in Kyoto, Japan.

Neither the Chinese study, which was not randomized, nor the Japanese studies, which were not blinded, provides definitive evidence that clopidogrel is superior to aspirin following DAPT in patients with PCI, but Jordon Safirstein, MD, medical director of the Cardiac Cath Lab at Morristown Medical Center in Morristown, New Jersey, considers the data informative.

“I believe prior to these studies, many of us in the interventional cardiology community felt that clopidogrel would pose a more significant bleeding risk to stable patients, so we defaulted to a baby aspirin,” Safirstein said.

These data provide evidence that “regardless of bleeding risk or lesion complexity, clopidogrel was associated with less adverse events,” Safirstein said. In the absence of higher-quality data, Safirstein said these data “seem to support” clopidogrel as the antiplatelet of choice for single-agent antiplatelet therapy after patients have tolerated 12 months of DAPT.

Wang reported having no potential conflicts of interest. Watanabe reported having financial relationships with Abbott Medical Japan, Abiomed, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Kowa, and Otsuka. Safirstein reported having no potential conflicts of interest.