EVOLVE Short DAPT in Print: P2Y12 Decisions Can Safely Be Made Case-by-Case

Three-month results of the EVOLVE Short DAPT trial, now in print, support the safety of stopping dual antiplatelet therapy (DAPT) in elderly patients at high bleeding risk if necessary, although the decision to do so should be made on a case-by-case basis.

The findings, originally released at TCT 2019 and now published online March 1, 2021, ahead of print in Circulation: Cardiovascular Interventions, show that between 3 and 15 months after PCI with Synergy everolimus-eluting stents (Boston Scientific), patients who dropped their P2Y12 inhibitor after only 3 months had a similar adjusted risk of the combined endpoint of death and MI when compared with controls who stayed on DAPT for 12 months (5.6% vs 5.7%; P = 0.0016 for noninferiority).

Additionally, the rate of stent-related definite/probable stent thrombosis was only 0.2% between 3-15 months in those who followed the shortened DAPT protocol, a significantly lower rate than the prespecified performance goal of 1.0%.

Lead author Ajay J. Kirtane, MD (NewYork-Presbyterian Hospital/Columbia University Irving Medical Center, New York, NY), told TCTMD this study helps put past clinical behavior into perspective, but should give confidence to clinicians who now feel the need to stop DAPT in these patients.

“Ten years ago right after DES came out, it was one of those scenarios that if you had a patient that had to come off for whatever reason or came into the office and told you they hadn't been taking their dual antiplatelet therapy, we would almost give the patient samples of medicine or call the pharmacy ourselves and tell them the patient was going to come to the pharmacy, so that they could immediately be back on their DAPT,” he recalled. “Studies like this one and others really sort of emphasize that that's probably not [needed] for a large proportion of patients, and especially those that are at high bleeding risk.”

Nonetheless, the biggest outstanding question relates to the benefits in terms of reducing non-stent-related events associated with DAPT duration, according to Kirtane.

“It's actually very hard in some ways to study a shorter duration versus a longer duration in a randomized fashion, because it may be that the longer duration is preventing events that have nothing to do with the stent—they just may be events the patient is going to have in areas outside of the stent alone,” he said. “But it'd be good to quantify that with contemporary DES, because that's what the DAPT study tried to study but that had earlier generations of stents.”

Kirtane said that while it seems safe to stop DAPT earlier, their study included only selected patients. “This study did not include patients that had acute myocardial infarctions or were super high risk for stent thrombosis,” he stressed. “I don't think people can just indiscriminately take studies like this and say [for] every single patient we can stop earlier.”

Davide Capodanno, MD, PhD (University of Catania, Italy), who wrote an editorial accompanying the study, told TCTMD that DAPT duration is a “moving target especially when you run these studies in this evolving field.” For example, the control group of this study “is probably no longer contemporary” given that current US and European guidelines suggest 6 months of DAPT for patients at high bleeding risk, he said. “Of course, they didn't randomize against an active comparator because it's probably not ethical to randomize patients at high bleeding risk versus 12 months, so they used a historical cohort. But at the same time, probably now the real comparator is versus 6 months. It's the next question.”

Also, a comparison using other stents and a variety of DAPT durations would be helpful in the future, according to Capodanno.

For now, he advised, clinicians should first recognize how commonly patients are at high bleeding risk. “Probably they are underdetected, while they represent almost half of patients that are receiving PCI,” Capodanno said. As for the best strategy when DAPT is no longer an option, dropping aspirin is not advised and de-escalation has not yet been studied enough in this population, he said; instead, stopping the P2Y12 inhibitor “is the most-used strategy.”

Both the ongoing MASTER DAPT and TARGET SAFE trials of 4,300 and 1,720 patients, respectively, should help bring more clarity to the trade-off between bleeding and thrombotic events associated with varying DAPT durations in high-bleeding-risk patients, Capodanno said.

MASTER DAPT, Kirtane noted, is studying the Ultimaster sirolimus-eluting stent (Terumo), not yet available in the United States.

“The challenge for clinicians is that they often like to have a very formulaic answer to clinical scenarios—so I always give X duration of dual antiplatelet therapy for my patients—and I think it's really important to emphasize that X is not a single number,” Kirtane said. “It depends on a variety of risks of the patient and has to be thought of for every patient. For every patient that I put a stent in, irrespective of stent type, you need to make the decision as to what's optimal for the patient, but having data like this gives one more options as a clinician.”

Capodanno also pointed to a recently published tool based on Academic Research Consortium (ARC) criteria to help clinicians balance the risks in individual patients. “It's difficult as an exercise but probably what we should do more and more,” he said.

Note: Kirtane is a faculty member of the Cardiovascular Research Foundation, the publisher of TCTMD.