P2Y12 inhibitor monotherapy after coronary stenting

1. In patients undergoing percutaneous coronary intervention, 3-month dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy showed comparable cardiovascular outcomes to 12-month DAPT.

Evidence Rating Level: 2 (Good)

Several randomized trials have showed that after percutaneous coronary intervention (PCI), short-duration DAPT (dual antiplatelet therapy) followed by P2Y12 inhibitor monotherapy reduced bleed risk while providing comparable protection against recurrent ischemic events compared to 12-month DAPT. In STOPDAPT 2, 1-month DAPT followed by clopidogrel monotherapy showed a reduction in a composite endpoint of cardiovascular and bleeding events. More potent P2Y12 inhibitors, such as ticagrelor and prasugrel, may provide more consistent inhibition against platelet aggregation, but have only been indicated for patients with acute coronary syndrome. While clopidogrel is by far the most frequently prescribed P2Y12 inhibitor, data with clopidogrel monotherapy remains limited due to interpatient variability in response. This pre-specified analysis of an open-label, non-inferiority, randomized trial, The Smart Angioplasty Research Team: Comparison Between P2Y12 Antagonist Undergoing Implantation of Coronary Drug-Eluting Stents (SMART-CHOICE), included 2 993 patients (58.2% presenting with ACS) who had undergone PCI with drug eluting stent (DES). Patients received either P2Y12 inhibitor monotherapy after 3-month DAPT or 12-month DAPT. Clopidogrel was the main P2Y12 inhibitor used, received by 77.2% of the study population, with the remaining 22.8% using potent P2Y12 inhibitors (18.4% with ticagrelor, 4.3% with prasugrel). Regardless of P2Y12 inhibitor used, no significant differences were found between the groups with P2Y12 monotherapy and 12-month DAPT in the composite primary endpoint of all-cause death, myocardial infarction or stroke (MACCE) at 12 months after the index procedure. Among patients receiving clopidogrel, consistent treatment effects were shown across various subgroups, such as ACS, diabetes, and multivessel intervention. Among patients receiving potent P2Y12 inhibitors, there was a significantly lower risk of bleeding in the group who received P2Y12 inhibitor monotherapy compared to the DAPT group (HR 0.33, p=0.03). Of note, patient adherence to antiplatelet treatment was lower in the P2Y12 inhibitor monotherapy group compared to the DAPT group; nonetheless, both the per-protocol analysis and the intention-to-treat analysis showed similar results. As well, this study was conducted in a Korean population. Given a higher prevalence of CYP2C19 loss-of-function genotype, resulting in poorer metabolization of clopidogrel, among East Asians, these study results will need to be applied carefully to other groups. While this study demonstrated comparable cardiovascular outcomes between the use of 3-month DAPT followed by clopidogrel monotherapy and 12-month DAPT, further studies powered to compare different arms between P2Y12 inhibitors would be necessary.

Click to read the study in BMJ

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