An entire year of dual-antiplatelet therapy may be no better at limiting ischemic events or death than a shorter course for patients who have undergone percutaneous coronary intervention with a drug-eluting stent.
The two trials, which tested dual-antiplatelet therapy (DAPT) regimens of 3 months and 1 month, are also noteworthy for giving a P2Y12 inhibitor after DAPT instead of aspirin monotherapy, which is a more common approach. Each randomized about 3,000 patients.
According to lead authorof Sungkyunkwan University in Seoul, South Korea, and colleagues, who conducted the first trial (SMART-CHOICE), both shorter and longer DAPT regimens with aspirin have been associated with shortcomings.
Specifically, shorter duration DAPT with subsequent aspirin monotherapy carries increased risks of MI and stent thrombosis, the investigators wrote. “Conversely, prolonged DAPT increases the risk of bleeding, which offsets the benefit from reducing recurrent ischemic events. Therefore, neither prolonged DAPT nor short-duration DAPT followed by aspirin monotherapy is fully satisfactory.” Because of these shortcomings, the investigators suggested that developing novel strategies “is of paramount importance.”
The multicenter trial by Dr. Hahn and colleagues, conducted in South Korea, involved 2,993 patients undergoing percutaneous coronary intervention with drug-eluting stents. Patients were randomized to receive either standard DAPT with aspirin and a P2Y12 inhibitor for 12 months, or aspirin plus a P2Y12 inhibitor for 3 months followed by 9 months of P2Y12 monotherapy. Patients were stratified by enrolling center, clinical presentation, type of stent, and type of P2Y12 therapy. Stents were limited to those eluting cobalt-chromium everolimus (Xience Prime, Xience Expedition, or Xience Alpine; Abbott Vascular), platinum-chromium everolimus (Promus Element, Promus Premier, or SYNERGY; Boston Scientific), or sirolimus (Orsiro; Biotronik). Acceptable P2Y12 therapies were clopidogrel, ticagrelor, and prasugrel. The primary endpoint was a composite of major adverse cerebrovascular and cardiac events, including stroke, MI, or all-cause death, at 12 months after percutaneous coronary intervention. A number of secondary endpoints were also evaluated, such as bleeding rate, stent thrombosis, and the individual components of the primary endpoint.
Almost all patients (95%) in the DAPT group adhered to the study protocol, while a smaller proportion (79%) followed P2Y12 monotherapy as described. Still, for both groups, more than 97% of patients completed 1-year follow-up. Primary endpoint analysis showed that the cumulative rate of major adverse cerebrovascular and cardiac events was similar between both groups, at 2.9% in the P2Y12 group versus 2.5% in the DAPT group, which was statistically significant for noninferiority (P = .007). Per-protocol analysis supported this finding.
Similarly, the components of the primary endpoint – stroke, MI, or all-cause death – did not vary significantly between groups. No significant difference was detected for the risk of stent thrombosis. Although the major bleeding rate was comparable between groups, the overall bleeding rate was significantly lower in the P2Y12 inhibitor group than the DAPT group (2.0% vs. 3.4%; P = .02); this finding also was supported by per-protocol analysis (1.8% vs. 3.1%; P = .04).
The investigators proposed several explanations for the results. “First, aspirin might provide little additional inhibition of platelet aggregation in the presence of a P2Y12 inhibitor. … Second, the risk of bleeding was significantly lower with P2Y12 inhibitor monotherapy than with DAPT in the present study.”
They noted that second-generation drug-eluting stents were used, which have been shown to significantly reduce MI and stent thrombosis, compared with first-generation products.