Smart-choice trial_P2Y12 inhibitor monotherapy in complex PCI

P2y12 inhibitor monotherapy following short-term dual antiplatelet therapy in complex percutaneous coronary intervention: a post-hoc analysis of smart-choice trial.

In patients with complex percutaneous coronary interventions (PCIs), P2Y12 inhibitor monotherapy, mostly clopidogrel, following short-term dual antiplatelet therapy (DAPT) did not increase ischemic events compared with 12 months of DAPT.

Key Takeaway

• At 1 year, patients with complex PCIs had a higher risk of ischemic events and similar risk of bleeding events than those with non-complex PCIs.
• P2Y12 inhibitor monotherapy, mostly with clopidogrel, following 3 months of DAPT resulted in favorable ischemic outcomes comparable to the standard 12 months of DAPT for complex PCIs.

Why This Matters

• It remains uncertain whether P2Y12 monotherapy, especially clopidogrel, following short-term DAPT is associated with favorable outcomes in patients with complex PCI.
• This post-hoc analysis of SMART-CHOICE trial investigated the efficacy and safety of P2Y12 inhibitor monotherapy, mostly clopidogrel (78%), following short-term DAPT vs 12 months of DAPT in complex PCI.

Study Design

• This was a post-hoc analysis of the SMART-CHOICE trial (NCT02079194), a multicenter, prospective open-label randomized clinical trial:
  • Patients were allocated to two groups before PCI: (1) DAPT (aspirin + P2Y12 inhibitor) for 3 months, followed by 9 months of P2Y12 inhibitor monotherapy (2) DAPT for 12 months
• Complex PCI was defined by at least one of the following features:
  • 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation PCI with ≥2 stents implanted, and a total stent length of ≥60 mm
• Primary efficacy endpoint included major adverse cardiac and cerebrovascular event (MACCE), defined as the composite of all-cause death, myocardial infarction, or stroke at 12 months after the index procedure.
• Primary safety endpoint included bleeding defined as Bleeding Academic Research Consortium (BARC) types 2–5 at 12 months after the index procedure.

Key Results

• A total of 2,993 patients at 33 hospitals were randomized including 498 treated with complex PCIs and 2,495 undergoing non-complex PCIs
  • 76.3% (380/498) underwent complex PCIs and 83.8% (1961/2495) non-complex PCIs were exposed to clopidogrel-based therapy
• At 1 year, compared to the non-complex PCIs group, patients in the complex PCI group had higher rates of MACCE (4.0% versus 2.3%; hazard ratio [HR] = 1.74; 95% confidence interval [CI]: 1.05–2.89, P = 0.033), all-cause death (2.6% versus 1.0%, HR = 2.52, 95% CI: 1.30–4.90, P = 0.007), cardiac death (1.6% versus 0.6%, HR = 2.51, 95% CI: 1.08–5.88, P = 0.033), and stent thrombosis (0.6% versus 0.1%, HR = 7.53, 95% CI: 1.26–45.06, P = 0.027).BARC types 2–5 bleeding showed similar rates in both the groups (2.6% versus 2.6%, HR = 1.02; 95% CI: 0.56–1.86, P = 0.939).
• Effects of DAPT and P2Y12 inhibitor monotherapy in the complex and non-complex PCI groups
  • In non-complex PCI
    • MACCE rates: P2Y12 monotherapy showed similar MACCE rates compared with the DAPT group (2.6% versus 2.1%; HR = 1.27; 95% CI: 0.76–2.14; P = 0.359)
    • Bleeding BARC type 2–5: Significantly lower in P2Y12 group than DAPT group (1.9% versus 3.3%; HR = 0.57; 95% CI: 0.34–0.96; P = 0.033)
  • In complex PCI
    • MACCE rates: Similar in both groups (3.8% versus 4.2%; HR = 0.92; 95% CI: 0.38–2.21; P = 0.853)
    • Bleeding BARC type 2–5: lower in P2Y12 monotherapy group than DAPT group without statistical significance (1.9% versus 3.4%; HR = 0.58; 95% CI: 0.19–1.77; P = 0.340)
• The interaction was not statistically significant between complex and non-complex PCI groups with MACCE (Pinteraction = 0.483) and BARC bleeding types 2–5 (P_interaction = 0.904).

Limitations

• This study on complex PCI was not pre-specified in the protocol, and thus the findings must only be interpreted as hypothesis-generating.
• Complexity of coronary anatomy and lesions were not reviewed by an angiographic core laboratory but were site-reported.
• P2Y12 inhibitor monotherapy was associated with fewer bleeding events in complex PCI without statistical significance due to type II error associated with a small sample size.
• These findings cannot be generalized to Western patients because all study participants were East Asians.

MAT-BH-2300025/v1/Jan2023