One month of dual antiplatelet therapy after PCI non-inferior to standard duration: results from MASTER DAPT.

Key Points:

• Patients with high bleeding risk who were treated with PCI with an Ultimaster stent were randomized to either standard care dual antiplatelet therapy (DAPT) or abbreviated DAPT starting after 30 days of DAPT post PCI. Standard DAPT was defined as an additional 2 or 5 month duration (with or without anticoagulation, respectively) followed by single antiplatelet therapy (SAPT) for up to 11 months following randomization. Abbreviated DAPT was defined as immediate DAPT discontinuation followed by SAPT for 11 months (or 5 months if anticoagulation was indicated).
• The three primary endpoints included the following outcomes at 1 year: a) net adverse clinical events (NACE), b) major adverse cardiac and cerebral events (MACCE), and c) major or clinically relevant non-major bleeding (MCB).
• Treatment with abbreviated DAPT was noninferior to standard DAPT for NACE and MACCE. Abbreviated DAPT resulted in lower major or nonmajor bleeding.

Standard of practice after placement of drug-eluting stents has generally involved up to a year of dual antiplatelet therapy (DAPT). However, this strategy poses a unique challenge for patients with elevated bleeding risk, for whom the risk of major bleed may potentially outweigh the benefit of extended antithrombotic therapy.  Several recent trials have examined the use of abbreviated DAPT, including STOPDAPT-2, GLOBAL LEADERS, and Onyx ONE Clear. However, the results of these studies were complicated by either lack of randomization or not being fully representative of the patient populations of interest (i.e., primarily including patients at low ischemic or bleeding risk). The aim of the Management of High Bleeding Risk Patients Post Bioresorbable Polymer Coated Stent Implantation With an Abbreviated Versus Prolonged DAPT Regimen (MASTER DAPT) clinical trial (NCT03023020) was to evaluate the efficacy and safety of an abbreviated DAPT course on patients with high bleeding risk undergoing PCI with drug-eluting stent. In a Hot Line presentation at the 2021 European Society of Cardiology Conference today, Dr. Marco Valgimigli (University of the Italian Switzerland, Lugano) and his team presented the results of the MASTER DAPT trial.

The MASTER DAPT study was a multicenter, randomized, international clinical trial. Patients were all treated with an Ultimaster stent, a sirolimus-eluting stent with an open cell 2-link design and abluminal, PDLLA-PCL gradient polymer coating. No restrictions were placed as to the clinical context for requiring the stent or the complexity of received PCI. All recruited patients were required to have high bleeding risk. Patients at high bleeding risk were defined as those with at least one of 10 criteria, including a) clinical indication to oral anticoagulants (OAC) for >12 months, b) recent (<12 months) non-access site bleeding episode(s) which required medical attention, c) previous bleeding episode(s) which required hospitalization if the underlying c

ause has not been definitively treated, d) age >75, e) systemic conditions associated with increased bleeding risk, f) documented anemia (Hb <11g/dL) or transfusion within 4 weeks, g) use of chronic steroids or NSAIDS, h) malignancy with high bleeding risk, i) any previous stroke, or TIA within 6 months, or j) PRECISE DAPT score >25. Relevant exclusion criteria included the placement of stents or treatment of in-stent thrombosis/restenosis within 6 months of the index use of Ultimaster stent, or any previous use of bioresorbable scaffolds.

A total of 4,579 patients were randomized, all of whom were required to be free from adverse cardiovascular events within a month of the index PCI and received a month of DAPT prior to randomization. 2,295 received abbreviated DAPT therapy, which involved stopping DAPT and then either a) continuing SAPT until the end of the trial or b) up to an additional five months along with ongoing clinically indicated OAC. 2,284 patients received standard DAPT, which involved either a) continuing DAPT for at least an additional 5 months or b) two months along with clinically indicated OAC, either of which was followed by SAPT. The median DAPT duration in the abbreviated group was 34 days from the date of the index PCI and 193 days in the standard care group.

The three primary endpoints (all evaluated at 335 days) were as follows: a) net adverse clinical events (NACE, defined as a composite of all-cause death, MI, stroke, and major bleeding), b) major adverse cardiac and cerebral events (MACCE, the composite of all-cause death, MI, and stroke), and c) major or clinically relevant non-major bleeding. The first two outcomes were assessed for noninferiority, and the third for superiority. NACE occurred in 7.5% the abbreviated DAPT group and 7.7% in the standard care group (p<0.001 for noninferiority); MACCE occurred in 6.1% and 5.9% of patients respectively (p=0.001 for noninferiority). Both NACE and MACCE met noninferiority. Major bleeding was significantly elevated in the standard care group compared to the abbreviated DAPT group (9.4% vs 6.5% respectively, p<0.001, NNT ~35).

When discussing the implications of the study at the ESC Congress, Dr. Valgimigli stated: “The message of the study [for clinicians] is very clear…we can go short [DAPT] for 30 days and then continue with either aspirin or a P2Y12 inhibitor—which of the two is better, we did not assess…high bleeding risk patients may receive 30 days of DAPT, and [this] may actually be safer.” The major limitations of the study include heterogeneity in the duration of DAPT in the standard care arm, as well as heterogeneity in selection of SAPT and oral anticoagulant strategy.

The associated manuscript has been published in the New England Journal of Medicine.