Three-year outcomes from the SMART-CHOICE trial have shown that P2Y12 inhibitor monotherapy was associated with a lower risk of clinically relevant major bleeding than prolonged dual antiplatelet therapy (DAPT) among patients undergoing percutaneous coronary intervention (PCI).
The long-term follow-up from the Korean randomised clinical trial, published in JAMA Cardiology, suggest that long-term maintenance of P2Y12 inhibitor monotherapy may be a promising antiplatelet strategy after PCI, according to study authors Ki Hong Choi (Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea) et al.
Involving 2,993 patients from 33 hospitals in Korea, 1,495 patients were randomised to receive either P2Y12 monotherapy after three months of DAPT, and 1,498 to receive prolonged DAPT.
Investigators assessed the primary endpoint of major adverse cardiac and cerebrovascular events (MACCE), comprising of a composite of all-cause death, myocardial infarction (MI), or stroke, at three years, with secondary endpoints including bleeding, defined as Bleeding Academic Research Consortium (BARC) types 2–5, and major bleeding, BARC types 3–5.
One -year results for the trial were reported at the American College of Cardiology’s (ACC 68th annual scientific session in 2019, and found that 12 months after the index procedure, for the primary endpoint of MACCEs, P2Y12 inhibitor monotherapy was non-inferior to standard therapy of 12-month DAPT.
Writing in JAMA Cardiology Choi et al report that at three years, the primary endpoint occurred in 87 patients (6.3%) in the P2Y12 inhibitor monotherapy group and 83 (6.1%) in the prolonged DAPT group (hazard ratio [HR] 1.06, 95% confidence interval [CI] 0.79–1.44, p=0.69).
Furthermore, the authors report that P2Y12 inhibitor monotherapy significantly reduced the risk of bleeding with incidents of bleeding reported in 112 patients (3.2%) when compared to 44 (8.2%) in the prolonged DAPT group (HR 0.39, 95% CI 0.28–0.55, p<0.001). Incidence of major bleeding stood at 17 (1.2%) for the P2Y12 inhibitor monotherapy group compared to 31 (2.4%) in the prolonged DAPT group (HR 0.56, 95% CI 0.31–0.99, p=0.04).
The landmark analyses between three months and three years and per-protocol analyses showed consistent results, the investigators add.
“The current extended follow-up of the SMART-CHOICE study reports three-year ischaemic and bleeding outcomes between patients who received three months of DAPT followed by P2Y12 inhibitor monotherapy and those who received prolonged DAPT,” Choi et al write in JAMA Cardiology. “In accordance with the one-year results from the SMART-CHOICE trial, we found that the two treatments had comparable effects in preventing ischaemic events across three years,” the authors add.
Furthermore, they write: “The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI. Future A-CLOSE and SMART-CHOICE III trials will be helpful to confirm our findings.”
The study team note several limitations of their finding, including that all endpoints in the three-year analysis are exploratory as the completion of follow-up rate is 92.5%, while also noting that the treatments were open-label, “reflecting the impossibility of masking for an antiplatelet strategy”. However, all outcomes were adjudicated by an independent committee blinded to the treatment group, they add.
Though the three-year risk of ischaemic cardiovascular events did not show a statistically significant difference between the two groups, this result must be interpreted cautiously because of the limited number of events and sample size, the authors write in their conclusion.
Findings of the SMART-CHOICE are accompanied in JAMA Cardiology by an editorial comment from Ajay Kirtane (Columbia University Irving Medical Center New York-Presbyterian Hospital, New York, USA) and Roxana Mehran (Icahn School of Medicine at Mount Sinai, New York, USA), in which they advocate a “patient-directed” approach to antiplatelet therapy.
“These data should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk, although SMART-CHOICE was underpowered to rigorously assess ischaemic differences, so caution is warranted,” Kirtane and Mehran note. “For patients at greatest risk for recurrent ischaemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualised treatment decisions. To some,
the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions.”
