The appropriate duration of dual antiplatelet therapy in patients at high risk for bleeding after the implantation of a drug-eluting coronary stent remains unclear. Valgimigli et al have shown that 1 month of dual antiplatelet therapy (DAPT) is noninferior to the continuation of therapy for at least 2 additional months with regard to the occurrence of net adverse clinical events and major adverse cardiac or cerebral events; along with the added advantage of lower incidence of major or clinically relevant nonmajor bleeding. The results of this multicenter, randomized, open-label, noninferiority trial with sequential superiority testing were published in the latest issue of NEJM last week.
Prolonged dual antiplatelet therapy is the treatment of choice for patients with an acute coronary syndrome who have undergone percutaneous coronary intervention (PCI) with a drug-eluting stent. The rationale is anchored in the understanding that drug-eluting stents impair the vascular healing process, because exposure of the metal in the stent serves as a nidus for stent thrombosis. But the ideal duration of this therapy is still a gray area for stable angina patients undergoing PCI.
The evolotion of recent 3rd and 4th generation stents has resulted in retention of their anti-restenosis properties while shortening their drug-eluting properties to minimize the exposure of the metal to platelets and fibrin. This may allow for shorter DAPT therapy for patients who are at high bleeding risk and cannot tolerate prolonged DAPT regimens.
MASTER DAPT trial involved 4579 patients, the majority of whom had stable heart disease (51% of the patients), who were randomly assigned to receive 30 days or 6 months of dual antiplatelet therapy (i.e., abbreviated therapy or standard therapy) and were then followed up to 1 year.
The choice of the single antiplatelet therapy after randomization in the abbreviated-therapy group, at 30 days after PCI, was decided by the investigator and was predominantly clopidogrel (in 56% of the patients) or ticagrelor (in 14%); 31% of the patients in this group received aspirin as single antiplatelet therapy.
The three ranked primary outcomes were:
1. Net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding),
2. Major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and
3. Major or clinically relevant nonmajor bleeding; cumulative incidences were assessed at 335 days.
The cumulative incidence of net adverse clinical events was 7.5% in the abbreviated-therapy group and 7.7% in the standard-therapy group, which met the noninferiority criteria established for the trial (P<0.001).
These findings were driven by a cumulative incidence of major bleeding that was approximately 30% lower in the abbreviated-therapy group than in the standard-therapy group. The incidence rate of MACCE also met the non-inferiority criteria.
Major or clinically relevant nonmajor bleeding occurred in 148 patients (6.5%) in the abbreviated-therapy group and in 211 (9.4%) in the standard-therapy group, that satisfied the pre-decided superiority criteria for abbreviated therapy group.
The finding that the use of abbreviated dual antiplatelet therapy may be reasonable in patients at increased bleeding risk should also be viewed in the context of the use of the Ultimaster drug-eluting stent (Terumo) in this trial. This is a biodegradable-polymer sirolimus-eluting stent. However, abbreviated therapy may not be applicable to all later-generation drug-eluting stents, so caution should be used before short dual antiplatelet therapy is adopted more broadly.
"The findings of Valgimigli and colleagues are important and move us toward a shorter and simpler antithrombotic strategy after PCI. Concomitant shorter antiplatelet monotherapy in the context of chronic disease after the implantation of a drug-eluting stent represents a major shift. This news is welcome for patients at high risk for bleeding after stent placement", writes E. Magnus Ohman, M.B in an accompanying editorial.
Source: NEJM:
1. DOI: 10.1056/NEJMoa2108749
2. DOI: 10.1056/NEJMe2112747