Abbreviated DAPT can be safe for patients with high bleeding and ischemic risk: MASTER-DAPT substudy

Key Points:

• In this pre-specified MASTER DAPT sub-study, patients with high bleeding risk and high ischemic risk (the latter of which was defined as those who have had a myocardial infarction within the last 12 months) 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 with anticoagulation).
• The three co-primary endpoints included the following at one 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 not significantly different from standard DAPT for NACE and MACCE in patients with high ischemic risk. Abbreviated DAPT resulted in lower major or nonmajor bleeding. There were no significant differences between the patients with high ischemic risk and those without.

Standard of practice after placement of drug-eluting stents involves at least a year of dual antiplatelet therapy (DAPT); however, this strategy may pose considerable harm to patients at high bleeding risk.  Several recent trials have examined the use of abbreviated DAPT, including STOPDAPT-2, GLOBAL LEADERS, and Onyx ONE Clear. More recently, the MASTER DAPT (NCT03023020) trial, first presented at the 2021 European Society of Cardiology Conference, evaluated the efficacy and safety of an abbreviated DAPT course on patients with high bleeding risk undergoing PCI with drug-eluting stent. In a breaking presentation at the 2021 Transcatheter Cardiovascular Therapeutics Conference today, Dr. Pieter Smits and his team presented the results of a pre-specified sub-study of the MASTER DAPT trial, which specifically included patients of high ischemic risk.

The MASTER DAPT study was a multicenter, randomized, international clinical trial across 140 hospitals worldwide. Patients were all treated with the sirolimus-eluting Ultimaster stent.  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 cause 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.  The sub-study specifically assessed outcomes in patients with high ischemic risk, which was defined as an MI within 12 months of presentation. 95% of these patients met these criteria due to an MI at the time of PCI, and 5% met them via an MI within the 12 months prior to PCI.

A total of 4,579 patients were randomized, of whom 1780 were designated as “high ischemic risk.” Of these, 914 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. 866 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 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. In patients at high ischemic risk, there was no difference in NACE (HR 0.83 [95% CI; 0.61-1.12], p=0.22) or MACCE (HR 0.86 [95% CI; 0.62-1.19], p=0.36) in the abbreviated DAPT group. The p-interaction when compared with the patients without high ischemic risk was not significant. Major bleeding was significantly reduced in the abbreviated DAPT group in patients with high ischemic risk (HR 0.65 [95% CI; 0.46-0.91], p=0.01). Similarly, there was no interaction when comparing with patients without high ischemic risk. There was also no difference in the secondary outcomes in the high ischemic risk subgroup between the two DAPT regimens, including MI, all-cause death, and stroke.

When discussing the implications of the study with Cardiology Now News, Dr. Smits stated: “In these bi-risk patients with high ischemic risk and high bleeding risk, we found that for NACE and MACCE endpoints …there was no difference in outcomes between the abbreviated or non-abbreviated DAPT arms in either the prior MI or the [normal ischemic] risk subgroups…For bleeding, we found a significant reduction in the abbreviated DAPT arm, which was consistent in patients with a prior MI or patients with no prior MI…As to whether this finding can be extended to different stents, that remains to be seen.”