OAC Analysis From MASTER DAPT Raises No Red Flags for Shorter DAPT

High-bleeding-risk (HBR) patients taking an oral anticoagulant (OAC), as well as those who were not, had similar rates of ischemic and net adverse events in the MASTER DAPT trial, no matter whether they were randomized to abbreviated dual antiplatelet therapy (DAPT) or to a standard regimen for at least 6 months after PCI.

Patients without an indication for OACs also had statistically fewer clinically relevant bleeds if randomized to the shorter DAPT. Patients taking OACs trended in the same direction, but the difference, as compared with OAC patients randomized to the more standard DAPT duration, was not statistically significant.

Full results from MASTER DAPT were released this past weekend at the European Society of Cardiology Congress 2021, as reported by TCTMD. One day later, Pieter Smits, MD, PhD (Maasstad Hospital, Rotterdam, the Netherlands), presented the prespecified OAC analysis from MASTER DAPT.

“The main message is that, although statistical significance was not reached, I think that 1-month DAPT in HBR patients, whether they are using OAC or not on OAC, it's still safe . . . [and it is likely] this also reduces bleeding,” Smits told TCTMD.

The OAC analysis was also published simultaneously in Circulation.

A High-Interest Group

In the overall results for MASTER DAPT, HBR patients implanted with a biodegradable-polymer, sirolimus-eluting stent who were randomized to discontinue DAPT 1-month post-PCI had roughly similar rates of both net adverse clinical events (NACE) and major adverse cardiac or cerebrovascular events (MACCE) as patients randomized to standard therapy (at least 2 months of additional DAPT), meeting the trial definition for noninferiority. For major and clinically relevant nonmajor bleeding, the abbreviated DAPT strategy proved superior to the standard approach.

At the time the study was presented, however, one of the big outstanding questions was whether an abbreviated DAPT approach would be safe and effective in people already taking OACs, a group that made up more than one-third of the study’s HBR population. In this group, patients were randomized after 1 month of mandatory DAPT to either stopping DAPT and continuing clopidogrel monotherapy for an additional 5 months, with OAC alone thereafter (the abbreviated group), or to continuing DAPT out to the 3-month mark, followed by clopidogrel to the 12-month mark, then OAC alone thereafter if required.

Among patients with an OAC indication in the trial, rates of NACE (all-cause death, MI, stroke, and BARC 3 or 5 bleeding) were not significantly different between DAPT groups, although rates were numerically lower in the abbreviated group (HR 0.83; 95% CI 0.60-1.15). By contrast, in patients with no OAC indication, NACE rates were nearly superimposable over the 12-month follow-up period (HR 1.01; 95% CI 0.77-1.33).

For MACCE, event rates across all four groups—OAC and no-OAC, abbreviated and nonabbreviated DAPT—were roughly similar (OAC indication: HR 0.88; 95% CI 0.60-1.30, non-OAC indication: HR 1.06; 95% CI 0.79-1.44).

There were no differences in clinically relevant nonmajor bleeding (BARC 2, 3, or 5), among OAC patients randomized to standard or abbreviated DAPT (HR 0.83; 95% CI 0.62-1.12), whereas a statistically significant difference was seen among patients not on OACs (HR 0.55; 95% CI: 0.41-0.74).

Of note, a larger proportion of OAC patients in the abbreviated group were nonadherent to their allocated antiplatelet regimen, such that a significant proportion of patients remained on antiplatelet therapy beyond the 6-month mark.

Smits, to TCTMD, characterized the requirement of stopping clopidogrel in these patients as “a real hurdle,” not just for physicians but also for patients, reflecting discomfort over the idea of not having this additional perceived protection against ischemic events. “Approximately 17% [of OAC patients] did not do that, and that was unfortunate,” Smits said, “and that prevented us from having a significant reduction in bleeding as well.”

In their presentation—but not in the Circulation paper—MASTER DAPT investigators performed a censor-weighted analysis to correct for nonadherence. This analysis, Smits noted, showed clinically relevant bleeding was significantly reduced in among OAC patients who stopped clopidogrel, as intended, at 6-months.

“The censor-weighted 6-month landmark analysis showed that stopping of single antiplatelet therapy at 6 months significantly reduced clinically relevant bleeding without increase of ischemic risk.” Smits said in concluding his presentation. He and his co-investigators plan to publish the censor-weighted analysis as a separate paper, he told TCTMD.

Robert W. Yeh, MD (Harvard Medical School, Boston, MA), commenting on the MASTER DAPT OAC analysis, said he previously had not been advising his PCI patients also taking OAC to discontinue all antiplatelet drugs after a short period of antiplatelet monotherapy. “But in the highest-bleeding-risk patients, this appears to be a reasonable option, especially in those with lower ischemic risk, for example, the stable CAD patients,” he told TCTMD in an email. “I think my practice may change a bit for high-bleeding-risk patients.”

For patients not taking an oral anticoagulant, he added, “I was slowly moving toward single antiplatelet therapy with a P2Y12 inhibitor, and this further bolsters that case in the HBR population.”

Yeh and others, discussing MASTER DAPT on Twitter, had expressed some anxiety around transitioning patients off antiplatelets within such a short window post-PCI. These data, he said, help to placate some of those concerns: “I hadn’t done OAC-only before, so I am a bit nervous like others, but this gives data to help reassure me that it may be a good strategy. I’ll certainly be cautious in whom I apply that strategy, but this, combined with the AFIRE data, clearly point to it as a potentially useful strategy in selected patients.”

Still to be clarified is how patients with less-stable disease might fare with this abbreviated strategy. According to Smits, the prespecified ACS subanalysis from MASTER DAPT has been submitted for presentation at the TCT 2021 meeting in November.