Clopidogrel vs aspirin: Which is superior for long-term antiplatelet monotherapy during the chronic maintenance phase after PCI?Results from the 10-year follow-up of the HOST-EXAM* trial favour clopidogrel over aspirin as chronic maintenance therapy after percutaneous coronary intervention (PCI) with a drug-eluting stent (DES).
“Aspirin is the most widely used standard antiplatelet agent, and clopidogrel is a recommended alternative,” noted Dr Hyo-Soo Kim from the Seoul National University Hospital, Seoul, South Korea, at ACC.26. “However, no trial has addressed which antiplatelet agent is the optimal choice during the chronic maintenance period after PCI with DES.”
“[In this analysis,] compared with aspirin monotherapy, clopidogrel monotherapy significantly reduced the risk of the primary endpoint (patient-oriented composite outcomes [POCO]) over a 10-year follow-up period,” Kim said.
The primary endpoint is a composite of all-cause death, nonfatal MI, stroke, readmission due to acute coronary syndrome (ACS), and major bleeding complications (BARC** type ≥3) at 24 months. [Kim, et al, ACC 2026]
In the intention-to-treat (ITT) analysis, the cumulative incidence of POCO was 3 percent lower with clopidogrel than with aspirin (25.4 percent vs 28.5 percent; hazard ratio [HR], 0.86; p=0.005). The Kaplan-Meier curves diverged at 1 year and continued to do so until year 10.
This pattern was consistently observed in the key secondary endpoints: thrombotic composite outcome (17.3 percent vs 20 percent; HR, 0.82; p=0.002) and any bleeding (BARC type ≥2; 9.1 percent vs 10.8 percent; HR, 0.81; p=0.020).
The thrombotic composite endpoint included cardiac death, nonfatal MI, ischaemic stroke, readmission due to ACS, and stent thrombosis.
The differences in thrombotic and bleeding outcomes were primarily driven by the lower rates of stroke (4.6 percent vs 6.4 percent; HR, 0.72; p=0.008), ACS-related readmission (8.7 percent vs 11 percent; HR, 0.75; p=0.002), and major bleeding (5.6 percent vs 7.7 percent; HR, 0.71; p=0.002) in the clopidogrel vs the aspirin group.
The superiority of clopidogrel over aspirin was also evident across most subgroups for the primary and key secondary endpoints.
The patterns favouring clopidogrel over aspirin were also seen in the per-protocol analysis (POCO: HR, 0.76, p<0.0001, thrombotic outcome: HR, 0.69; p<0.0001, and bleeding outcome: HR, 0.73; p=0.00025) and the landmark analysis at 2 until 10 years (HR, 0.82; p=0.0074, HR, 0.78; p=0.0055, and HR, 0.74; p=0.021, respectively).
In the per-protocol analysis, the clinical benefit of clopidogrel was driven by the lower rates of non-fatal MI (3 percent vs 4.8 percent; HR, 0.58; p=0.002), stroke (3.6 percent vs 6.7 percent; HR, 0.52; p<0.001), readmission due to ACS (7.5 percent vs 11.5 percent; HR, 0.61; p<0.001), and major bleeding (5.3 percent vs 8.2 percent; HR, 0.62; p<0.001).
Furthermore, the number needed to treat (NNT) decreased from the 2-year analysis to the current 10-year evaluation in both the ITT (from 51 to 33) and the per-protocol analyses (from 45 to 17).
“Our working hypothesis was that clopidogrel would be superior to aspirin in terms of POCO in the chronic maintenance period after PCI,” Kim said. Hence, Kim and colleagues sought to evaluate the two antiplatelet agents in patients who underwent PCI with a DES and maintained dual antiplatelet therapy (DAPT), who were event-free for 12 ± 6 months after PCI.
A total of 5,438 participants (mean age 64 years, 74 percent men) were randomized 1:1 to either clopidogrel or aspirin monotherapy. The median follow-up was 10.5 years after PCI (10.7 years in survivors). At randomization, 81 percent of participants were on DAPT (aspirin and clopidogrel).
The most prevalent clinical indication of PCI was unstable angina (36 percent), followed by stable angina (26 percent) and non-ST-segment elevation MI (19 percent). Ten percent of participants underwent PCI for a bifurcation lesion, 9 percent for a CTO*** lesion, and 97 percent received a second-generation DES.
“[Our results show that] clopidogrel may be considered as the preferred agent for long-term antiplatelet monotherapy during the chronic maintenance phase after PCI,” Kim concluded.
The findings also align with guidelines recommending indefinite post-interventional and maintenance treatment with single antiplatelet therapy after the initial 6–12 months of DAPT. [Eur Heart J 2019;40:87-165; J Am Coll Cardiol 2011;58:e44-e122]
“The continued divergence of event curves and the decreasing NNT over time suggests that the clinical benefit of clopidogrel is cumulative,” noted Kim and colleagues in the published manuscript. [Lancet 2026:S0140-6736(26)00422-8]
“The totality of contemporary evidence suggests that the role of aspirin as first-line lifelong antiplatelet therapy after PCI warrants reconsideration, especially in healthcare systems where clopidogrel is accessible and inexpensive,” they said.