Clopidogrel monotherapy trumps aspirin monotherapy in reducing CV events post-PCI

One year after undergoing percutaneous coronary intervention (PCI), high-risk patients on clopidogrel monotherapy have a reduced risk of multiple cardiovascular (CV) outcomes compared with those on aspirin monotherapy, according to a study presented at SCAI 2022.

Using the Fuwai PCI registry, the researchers identified 8,377 patients at high risk for both bleeding and thrombosis who had one clinical and one angiographic criterion based on inclusion criteria of the TWILIGHT trial. Of these, 7,392 high-risk patients did not experience any ischaemic or bleeding events at 12 months post-PCI and were adherent to dual antiplatelet therapy (DAPT*). The present analysis included 5,664 patients (mean age 58.5 years, 75.8 percent male) who received antiplatelet monotherapy (clopidogrel [n=1,974]; aspirin [n=3,690]) for >12 months without extended duration DAPT. Patients were followed up for a median 29 months.

At 12–30 months post-PCI, the incidence of net adverse clinical events (NACE), defined as a composite of all-cause death, myocardial infarction (MI), definite/probable stent thrombosis, stroke, or BARC** bleeding type 2, 3, or 5, occurred in a smaller proportion of patients on clopidogrel than aspirin monotherapy (2.5 percent vs 5.0 percent; hazard ratio [HR], 0.566, 95 percent confidence interval [CI], 0.403–0.795; p=0.001). [SCAI 2022, abstract A-46]

The risk of major adverse cardiac or cerebral events (MACCE; a composite of death, MI, stent thrombosis, or stroke) at 12–30 months was also significantly reduced with clopidogrel than aspirin monotherapy (1.0 percent vs 3.1 percent; HR, 0.451, 95 percent CI, 0.281–0.725; p=0.001).

All-cause death rate was also significantly lower with clopidogrel vs aspirin monotherapy (0.6 percent vs 1.6 percent; HR, 0.497; p=0.031), as were rates of CV death (0.2 percent vs 0.9 percent; HR, 0.343; p=0.029) and stroke (0.4 percent vs 1.4 percent; HR, 0.384; p=0.013).

The risk of major or clinically relevant non-major bleeding (BARC type 2, 3, or 5) at 30 months was numerically lower with clopidogrel vs aspirin monotherapy (1.5 percent vs 2.1 percent; HR, 0.729, 95 percent CI, 0.452–1.178; p=0.197).

Bleeding rates did not significantly differ between the clopidogrel and aspirin groups specifically TIMI*** minor or major bleeding (0.5 percent vs 0.7 percent; p=0.791), GUSTO*** moderate or severe bleeding (0.4 percent vs 0.7 percent; p=0.571), intracranial bleeding (0.1 percent each), or gastrointestinal bleeding (0.3 percent vs 0.6 percent; p=0.556).

“These findings show for the first time clopidogrel monotherapy is associated with reduced risk of long-term NACE and MACCE,” said study author Dr Hao-Yu Wang from the Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

“Our results may have important practical implications for determining the optimal treatment for patients requiring a single antiplatelet drug, either aspirin or clopidogrel, for secondary prevention of ischaemic events in a high-risk PCI population,” said Wang.

The results are specific to East Asian patients from a single institution and as such, may not be generalizable to other populations. The low incidence of bleeding and ischaemic events may also have affected the findings, the authors said.

“[O]ptimal antiplatelet monotherapy during the chronic maintenance period beyond 12 months after PCI with drug-eluting stents in high-risk patients in real-world settings remains unclear,” said Wang. Aspirin is the most common antiplatelet used beyond 1-year post-PCI “due to its proven net benefit in the setting of secondary CV prevention.”

“In this real-world study, clopidogrel monotherapy has effects on all-cause and CV mortality, as well as stroke compared with aspirin monotherapy; therefore, this strategy might be an effective alternative to aspirin for secondary prevention of CV disease,” Wang concluded.

Nonetheless, further research is necessary to assess the safety and efficacy of P2Y₁₂ inhibitor monotherapy beyond 1-year post-PCI, said Wang.