Another trial has added to the movement towards shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI).
In the MASTER DAPT trial involving patients at high risk for bleeding who had undergone implantation of a biodegradable-polymer sirolimus-eluting stent, switching from DAPT to single antiplatelet therapy at a median of 34 days after PCI was noninferior to the continuation of DAPT treatment for a median duration of 193 days with regard to the incidence of major adverse cardiac or cerebral events and was associated with a lower incidence of major or clinically relevant bleeding.
The results of the study were presented by Marco Valgimigli, MD, Cardiocentro Ticino Institute, Lugano, Switzerland, on August 28 at the virtual European Society of Cardiology (ESC) Congress 2021. They were simultaneously published online in the New England Journal of Medicine.
"It has been suggested in previous studies that if patients are at high bleeding risk, then they do not seem to derive ischemic benefit from prolonging DAPT, they just get the increased bleeding risk," Valgimigli said. "But this has never been prospectively tested until now."
He pointed out that patients at high bleeding risk are a large group, representing up to 40% of patients undergoing PCI, and the MASTER DAPT trial included "all-comer" high-bleeding-risk patients with no selection based on ischemic risk.
The trial was very well received by commentators at the ESC Hot Line presentation.
Chair of the session, Roxana Mehran, MD, Mount Sinai School of Medicine, New York, described the trial as "practice-changing."
Davide Capodanno, MD, University of Catania, Italy, said, "This is the first adequately powered, active controlled randomized study to look at duration of DAPT in high-bleeding-risk PCI patients. I will feel better now when I stop DAPT in these patients as now we have the evidence."
And Robert Byrne, MD, Mater Private Hospital, Dublin, Ireland, added: "This is a stand-out trial. We have become more comfortable with abbreviated DAPT in high-bleeding-risk patients, but definite evidence for this has been lacking until now. This study tells us that just 1 month of DAPT appears to be safe in that there was no increase in ischemic complications and there was a clear reduction in bleeding."
The MASTER DAPT study involved 4579 patients at high bleeding risk who had undergone implantation of a biodegradable-polymer sirolimus-eluting coronary stent (Ultimaster, Terumo). Around half the patients had PCI for acute coronary syndrome (ACS) and half had it electively. One month after PCI they were randomly assigned to discontinue DAPT immediately (abbreviated therapy) or to continue it for at least 2 additional months (standard therapy).
The three co-primary outcomes were net adverse clinical events (a composite of death from any cause, myocardial infarction, stroke, or major bleeding), major adverse cardiac or cerebral events (a composite of death from any cause, myocardial infarction, or stroke), and major or clinically relevant nonmajor bleeding, all assessed cumulatively at 335 days. The first two outcomes were assessed for noninferiority in the per-protocol population, and the third outcome for superiority in the intention-to-treat population.
Dual antiplatelet therapy consisted of aspirin plus a P2Y12 inhibitor. The choices of the type of P2Y12 inhibitor for DAPT and the type of monotherapy after the discontinuation of DAPT were at the discretion of the investigator. Clopidogrel was the most popular choice, used as monotherapy in 54% of the patients in the abbreviated-therapy group and as part of DAPT in 79% of patients in the standard-therapy group.
Results showed that net adverse clinical events occurred in 7.5% of the abbreviated-therapy group and in 7.7% of the standard-therapy group (difference, –0.23 percentage points; 95% CI, –1.80 to 1.33 percentage points; P < .001 for noninferiority).
Major adverse cardiac or cerebral events occurred in 6.1% of the abbreviated-therapy group and 5.9% of standard therapy group (difference, 0.11 percentage points; 95% CI, –1.29 to 1.51 percentage points; P = .001 for noninferiority).
Reduction in Bleeding Driven by BARC-2
Major bleeding or clinically relevant nonmajor bleeding occurred in 6.5% in the abbreviated-therapy group and in 9.4% in the standard-therapy group (difference, –2.82 percentage points; 95% CI, –4.40 to –1.24 percentage points; P < .001 for superiority).
"This is a highly statistically significant reduction in bleeding giving a number needed to treat of 35," Valgimigli said.
The lower risk for bleeding in the abbreviated-therapy group was mainly due to the lower incidence of clinically relevant nonmajor bleeding events (BARC type 2) in this group than in the standard-therapy group (4.5% vs 6.8%).
During the discussion, Byrne pointed out that the most serious type of bleeding (BARC type 3-5) was not reduced in the abbreviated DAPT group.
Valgimigli responded that the investigators were surprised about that because previous studies indicated that this most serious bleeding would be reduced, but he suggested that this may be explained by the standard group only receiving 3 to 6 months of DAPT rather than a year or more in previous studies. "Having said that, BARC-2 bleeding is not a trivial event," he added.
Can Results Be Applied to Other Stents?
Byrne also questioned whether the results can be applied to patients receiving other types of stents — not just Ultimaster, which is not available everywhere. Valgimigli highlighted the low rate of stent thrombosis seen with the Ultimaster stent and said, "I would be scared to assume these results are reproducible with other stents."
But Mehran challenged this view, saying, "I'm not so sure about that. I think we can probably extrapolate."
To theheart.org | Medscape Cardiology, Mehran added: "I think this is one of the much-needed studies in our field. For the first time, we have a randomized trial on duration of DAPT in high-bleeding-risk patients. The study was inclusive, and enrolled truly high-bleeding-risk patients, including those on oral anticoagulants."
"These results show that although high-bleeding-risk patients are at high risk of ischemic events, just 1 month of DAPT works well for them regardless, by reducing bleeding, net adverse clinical events, and without increasing ischemic events," she concluded.
In an editorial accompanying the publication, E. Magnus Ohman, MB, from Duke University, Durham, North Carolina, pointed out the wide CIs in the results, which he said introduced some uncertainly to the findings.
But he concluded that: "The findings of Valgimigli and colleagues are important and move us toward a shorter and simpler antithrombotic strategy after PCI."
To theheart.org | Medscape Cardiology, Ohman pointed out that the Ultimaster stent is not available in the United States. "We have to think about whether this stent would perform differently to other third- or fourth-generation stents. I wouldn't have thought so, but it is hard to say for sure."
"All in all, we are looking at shorter periods of DAPT now after PCI. Several trials have now suggested that is the way to go. The forthcoming US PCI guidelines should put all the studies together and come up with recommendations on different patient groups," he concluded.
Also commenting for theheart.org | Medscape Cardiology, Michelle O'Donoghue, MD, Harvard Medical School, Boston, Massachusetts, said, "The findings lend further support to growing evidence that we may be able to discontinue DAPT earlier after PCI in patients who are at high risk of bleeding. This is particularly true with newer-generation stents."
She added: "It was reassuring to see that risk of MACE [major adverse cardiac events] was grossly similar between the treatment arms for patients regardless of whether or not they had experienced a recent ACS. However, the key question that remains is whether clinicians should discontinue aspirin or a P2Y12 inhibitor if they are planning monotherapy."
Kurt Huber, MD, Wilhelminenhospital, Vienna, Austria, a commentator at the ESC press conference on the study, said, "We have already started, based on other studies, to shorten DAPT to 1 month (stable patients) and up to 3 months (ACS patients). Now we have additional data that the Ultimaster stent performs extremely well in this group of patients. We will use this stent much more in the future," he told theheart.org | Medscape Cardiology.
Several commentators said they would like to see the data on the patients receiving oral anticoagulants in the study before making firm conclusions on how to translate the results into clinical practice. "This is such an important group. It is difficult to interpret the results without this data," Ohman noted.
Patients receiving oral anticoagulants, who made up 36% of the study population, will be the subject of a separate report to be presented at the ESC meeting in the coming days.
The MASTER DAPT trial was supported by Terumo. Valgimigli reports research grants from Terumo, Abbott, and SMT and consulting or speaker fees from Terumo, Abbott, Daiichi Sankyo, Chiesi, Vesalio, Vifor, Avimedica, Medtronic, Boston Scientific, and Astra Zeneca. Ohman reports grants from Abiomed, grants from Chiesi USA, personal fees from Cara Therapeutics, Genentech, Imbria, Impulse Dynamics, Milestone Pharmaceuticals, Xylocor, Cytokinetics, Dispersol, Otsuka, Pfizer, Cytosorbent, Neurocrine, and Paradigm, outside the submitted work.
European Society of Cardiology (ESC) Congress 2021. Presented August 28, 2021.
N Engl J Med. Published online August 28, 2021. Abstract, Editorial
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Cite this: MASTER DAPT: 1 Month DAPT Enough After High-Bleeding-Risk PCI - Medscape - Aug 28, 2021.