P2Y12 inhibitor monotherapy after 3-month or 12-month dual antiplatelet therapy according to type of P2Y12 inhibitor in patients undergoing percutaneous coronary intervention

This prespecified analysis from the SMART-CHOICE trial demonstrated that among patients undergoing percutaneous coronary intervention (PCI), clopidogrel monotherapy after 3-month dual antiplatelet therapy (DAPT) showed comparable cardiovascular outcomes compared with 12-month DAPT.

Key Takeaway

  • In patients undergoing PCI, P2Y12 inhibitor monotherapy after 3-month DAPT and 12-month DAPT groups showed no statistically significant differences in the cumulative rates of major adverse cardiovascular and cerebrovascular events (MACCEs) in both patients treated with clopidogrel and potent P2Y12 inhibitors.
  • Risk of bleeding reduced in patients receiving monotherapy with potent P2Y12 inhibitors.

Why This Matters

  • One alternative to prolonged DAPT is short-term DAPT followed by P2Y12 inhibitor monotherapy (clopidogrel); however, there are concerns regarding clopidogrel monotherapy owing to its limitations, including delayed onset of action and wide individual variability in platelet inhibition.
  • This prespecified analysis of SMART-CHOICE trial compared P2Y12 inhibitor monotherapy after 3-month DAPT with 12-month DAPT according to P2Y12 inhibitor type among patients undergoing PCI.

Study Design

  • The SMART-CHOICE was an investigator-initiated, multicenter, open-label, non-inferiority, randomized trial that enrolled patients undergoing PCI with drug-eluting stents (DES) at 12 months after the index procedure and received antiplatelet therapy.
  • For this prespecified analysis, P2Y12 inhibitors were classified in two groups: clopidogrel and potent P2Y12 inhibitors (ticagrelor and prasugrel). • Inclusion criteria: Age ≥20 years; ≥1 coronary artery stenoses of ≥50% in a native coronary artery suitable for stent implantation; and successful PCI using DES for stable ischemic heart disease or acute coronary syndrome (ACS)
  • Primary endpoint: Occurrence of MACCEs (i.e., composite of all-cause death, myocardial infarction [MI], or stroke at 12 months after the index PCI)
  • Secondary endpoints: Cardiac death, stent thrombosis, Bleeding Academic Research Consortium (BARC) types 2–5 bleeding, BARC types 3–5 bleeding, and net adverse clinical and cerebral events

Key Results

  • Overall, 2,993 patients (mean age: 64 years) were enrolled at 33 sites in Korea (P2Y12 inhibitor monotherapy: n = 1,495; DAPT: n = 1,498). In total, 2,312 (77.2%) and 681 (22.8%) patients received clopidogrel and potent P2Y12 inhibitors, respectively.
  • For patients receiving clopidogrel, 12-month adherence to P2Y12 inhibitors was similar in P2Y12 inhibitor monotherapy (95.3%) and DAPT groups (96.9%).
  • For patients receiving potent P2Y12 inhibitors, rates of P2Y12 inhibitor use at 12 months were 93.8% vs 95.5% in P2Y12 inhibitor monotherapy vs DAPT groups.
  • Outcomes in patients receiving clopidogrel:
    • At 12 months, the P2Y12 inhibitor monotherapy and DAPT groups did not differ significantly regarding the cumulative rates of MACCE (3.0% vs 3.0%; univariable hazard ratio [HR] = 1.02; 95% confidence interval [CI]: 0.64–1.65; P = 0.93).
    • No significant differences were noted in the cumulative rates of cardiac death and stent thrombosis.
    • No significant differences were noted in risk of BARC types 2–5 bleeding (2.1% vs 2.9%; univariable HR = 0.71; 95% CI: 0.42–1.21; P = 0.21).
    • Across subgroups (including ACS, diabetes, and multivessel intervention), MACCEs following clopidogrel monotherapy vs DAPT were consistent.
  • Outcomes in patients receiving potent P2Y12 inhibitors:
    • At 12 months, P2Y12 inhibitor monotherapy and DAPT groups showed no significant heterogeneity in the cumulative rate of MACCE (2.4% vs 0.7%; univariable HR = 3.37; 95% CI: 0.77–14.78; P = 0.11; interaction P = 0.1).
    • Cumulative rates of all-cause death and MI were not significantly different.
    • No evidence of stent thrombosis was observed in both arms.
    • The P2Y12 inhibitor monotherapy group had significantly lower risk of BARC types 2–5 bleeding (1.5% vs 5.0%; univariable HR = 0.33; 95% CI: 0.12–0.87; P = 0.03; interaction P = 0.15).
  • Results of the per-protocol analysis and intention-to-treat analysis were similar.

Limitations

  • The study was not sufficiently powered to compare outcomes following treatment with each P2Y12 inhibitor.
  • Although adherence was lower with P2Y12 inhibitor monotherapy vs DAPT, results of per-protocol analysis and intention-to-treat analysis were similar.
  • Owing to the 2017 European Society of Cardiology guidelines recommendations, directly applying study results to patients undergoing elective DES stenting might be difficult.
  • The study included only Korean patients; considering the “East Asian paradox,” results should be carefully applied to Western population.
    Kim J, Jang WJ, Lee WS, Choi KH, Lee JM, Park TK, et al. P2Y12 inhibitor monotherapy after coronary stenting according to type of P2Y12 inhibitor. Heart. 2021. doi: 10.1136/heartjnl-2020-318821. Epub ahead of print. PMID: 33758008.

MAT-BH-2300008/v1/Jan2023