DENVER, CO — Shorter dual antiplatelet therapy (DAPT) is a reasonable option after ST-segment elevation MI (STEMI) in patients treated with second-generation drug-eluting stents (DES), results of the DAPT-STEMI trial suggest[1].
“For the first time in the modern DES era, this trial indicates that STEMI patients, similar to stable-angina patients, may not benefit from prolonged DAPT therapy beyond 6 months as currently recommended,” Dr Elvin Kedhi (Isala Hartcentrum, Zwolle, the Netherlands) said during a late-breaking trial session at TCT 2017.
US guidelines carry a class I recommendation for 12 months of DAPT for STEMI patients after primary PCI with DES due to ongoing thromboembolic risk. But nonrandomized data are emerging to support the safety of shortening DAPT duration to counterbalance the increased bleeding risk.
The prospective, noninferiority DAPT STEMI trial enrolled 1100 patients who underwent primary PCI with the Resolute Integrity zotarolimus-eluting stent (Medtronic) at 17 European centers. Patients who were event-free after completing 6 months of DAPT were then randomized to aspirin alone (n=433) or to continue DAPT for another 6 months followed by aspirin alone (n=437).
At 18 months of follow-up (2 years after PCI), the composite primary end point of all-cause mortality, MI, any revascularization, stroke, or TIMI major bleeding occurred in 4.8% of patients receiving aspirin alone and in 6.6% receiving DAPT.
This resulted in a hazard ratio of 0.73 (95% CI 0.41–1.27; P=0.26) and met the prespecified noninferiority margin of 1.66 (P=0.004), Kedhi said.
Rates of the individual components of the primary end point in the single and DAPT groups were:
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Mortality: 0.7% vs 1.4% (HR 0.51; 95% CI 0.13–2.02).
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MI: 1.8% vs 1.8% (HR 1.02; 95% CI 0.38–2.71).
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Revascularization: 3% vs 3.9% (HR 0.87; 95% CI 0.42–1.83).
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Stroke: 0.7% vs 0.7% (HR 1.02; 95% CI 0.21–5.03).
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Major bleeding: 0.2% vs 0.5% (HR 0.51; 95% CI 0.05–5.57).
Kedhi explained that lower-than-estimated event rates in both arms might reflect the trial design of randomizing only event-free patients at 6 months. Randomization was also lower than expected because of higher-than-expected withdrawals as well as treatment of nonculprit lesions outside the prespecified time window.
“Although a noninferiority margin of 1.66 might appear large, it should be noted that it represents the upper limit of the 95% confidence interval and that it takes into account the impact of random fluctuation in a trial like DAPT-STEMI,” he added.
Commenting for theheart.org | Medscape Cardiology, panelist Dr Robert Harrington (Stanford University, CA) said, “I don’t think it will impact practice, but I think it will impact research. What I mean by that is that the design limitations, big noninferiority margin, relatively small trial, and not enough events means it won’t change practice, but it’s a transition study. It gives us the opportunity to think about really tackling this problem.”
He added, “Think about it as almost pilot data that look reasonable. Now what we need to do is a much larger study with appropriate power.”
During the panel discussion, session moderator Dr Gregg Stone (Columbia University, New York, NY) said, “Interestingly, here we didn’t see a difference in any of the ischemic or the bleeding components, suggesting we may not have been powered to see either.”
Panelist Dr David Capodanno (University of Catania, Italy) questioned the generalizability of the results because of the low-risk population and said the composite end point, “which of course makes the trial feasible and we should not forget that,” makes it difficult to interpret the results.
“I believe the results are not conclusive and we don’t have the power certainly on the ischemic and bleeding end points,” he said.
During a press conference, Kedhi responded to a question about the high number of withdrawals, noting that following the poor results with the first-generation DES, European guidelines hammered home the point that STEMI patients needed at least 12 months of DAPT or would face a very high risk of stent thrombosis, MI, or death.
When the trial started in 2011, “It was impossible to convince people to go for 6 months [on DAPT]. They’d go to their house physician and they’d say, ‘Are you crazy? You can’t stop this.’ So to change this mentality will take time,” he said.
Press briefing moderator Dr Gary Mintz (Cardiovascular Research Foundation, New York, NY) said the elevated risk of bleeding with DAPT is important, particularly as the population ages, but that the message from DAPT-STEMI and the REDUCE trial is “extremely consistent.”
“Little by little, based on the hard safety and efficacy data, we can dial down DAPT,” he said.
The study was funded by Maasstad Cardiovascular Research. Kedhi reported receiving consulting fees/honoraria or institutional grants from Medtronic, Abbott, Meril, and OrbusNeich. Harrington discloses receiving grants or research contracts from AstraZeneca, the Medicines Company, Portola, St Jude Medical, Sanofi, Novartis, Bristol-Myers Squibb, and Jannsen; consulting or serving on speaker’s bureaus for Amgen, Gilead, Medscape, MyoKardia, the Medicines Company, and Bayer; and having equity interest in MyoKardia, Element Science, and Scanadu. Mintz disclosed research support and fees from Boston Scientific and has previously reported receiving grants from St Jude, grants and personal fees from Boston Scientific and Volcano, and personal fees from Acis.
Follow Patrice Wendling on Twitter: @pwendl. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.
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