Solo Aspirin After 3 Months of Post-Stent DAPT Safe in High-Bleed-Risk Patients: EVOLVE Short DAPT Study

September 27, 2019

SAN FRANCISCO — A study called EVOLVE Short DAPT has a message — lately a familiar one, albeit with a few twists — about antiplatelet therapy in patients treated with contemporary coronary drug-eluting stents (DES).

The single-group trial with almost 2000 patients joins a chorus of other studies presented here at Transcatheter Cardiovascular Therapeutics Conference 2019, including TWILIGHT, that support cutting back on the duration and intensity of the subsequent antiplatelet therapy intended to prevent in-stent thrombosis.

But EVOLVE Short DAPT was unusual for looking at a transition from dual antiplatelet therapy (DAPT) to single antiplatelet therapy starting 3 months after the procedure specifically in patients considered at high bleeding risk (HBR).

Such patients included those on chronic oral anticoagulation (OAC), who made up about 31% of the population studied; the two-thirds of patients who were 75 years or older whose risk of bleeding clinicians believed exceeded any likely benefit from prolonged DAPT; and those with a history of stroke, major bleeding, or renal failure.

Moreover, when patients who were event-free after 3 months went from DAPT to a single antiplatelet agent, it was the clopidogrel or other P2Y12 inhibitor they halted, not the aspirin. Those with events, which could have included stent thrombosis, continued on DAPT.

All patients in the study had received the everolimus-eluting SYNERGY stent, coated with a bioabsorbable polymer (Boston Scientific); none received it for an acute MI intervention.

The trial showed that 3 months of DAPT followed by single antiplatelet therapy was noninferior to DAPT continued for 12 months for the dual primary end points of death or acute myocardial infarction (MI) and of definite or probable stent-thrombosis over 15 months.

And the transition of the HBR patients to a single antiplatelet was not associated with an increased risk of major bleeding, defined by Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 criteria.

Only four patients who stopped DAPT at 3 months, or 0.3%, developed stent thrombosis over the full 15 months, with the caveat that the trial's exclusion criteria included complex stent-treated lesions, said Ajay M. Kirtane, MD, Columbia University and NewYork-Presbyterian Hospital, New York City, at a media briefing on EVOLVE Short DAPT.

That stent-thrombosis rate was well under the 1% performance goal established for the study (P < .0001), he said.

For the kind of HBR patients enrolled, EVOLVE Short DAPT supports use of the SYNERGY stent followed by a DAPT duration of only 3 months, said Kirtane, who was a trial principal investigator.

"The stent-thrombosis rate was low, which is the primary reason we do dual antiplatelet therapy," observed Ori Ben-Yehuda, MD, Cardiovascular Research Foundation, New York City, who moderated the media briefing. However, he noted, the study excluded patients with complex, high-risk lesions.

It excluded patients who, for example, had stenting of more than three lesions or for in-stent restenosis, left-main disease, bifurcations, vein grafts, or chronic total occlusions. So the cohort didn't necessarily reflect broad clinical practice.

Given that, Ben-Yehuda asked Kirtane and other panelists at the briefing how they would apply the study's results today, including the question of which antiplatelet should be dropped after 3 months.

The TWILIGHT study didn't have an aspirin-only single-antiplatelet group, Ben-Yehuda observed. If it had included one, "then we'd have the answer."

"I certainly wouldn't be the one to advocate saying 3 months of DAPT is the way to go for all patients treated with this particular stent or some of the others in studies that we've seen today," Kirtane said.

"There are many patients who have stents placed who need a surgery or have gastrointestinal bleeding. Previously people really struggled with how to keep them on dual antiplatelet therapy for up to a year because that's what the guidelines said."

EVOLVE Short DAPT and others in the crop of recent studies supporting briefer post-stent DAPT durations in a variety of patients, Kirtane said, should reassure clinicians that if DAPT has to be halted, "then patients are not going to thrombose their stents. It's not true in all patients — I mentioned the caveats of the enrolment group — but that's a good message for clinicians to have."

Although most of the other panelists also favored clopidogrel as the single-antiplatelet of choice after 3 months from coronary stenting, Davide Capodanno, MD, PhD, University of Catania, Italy, said he would approve of either that drug or prasugrel (Effient/Efient, Eli Lilly/Daiichi Sankyo), depending on the patient.

None of the panelists voiced a preference for aspirin as the single antiplatelet, per EVOLVE Short DAPT. "The benefits of aspirin were established in an era when many of the secondary prevention therapies that we have today were not available, like statins, ACE inhibitors, et cetera," Capodanno observed.

If the older trials that established aspirin for secondary prevention were repeated today, he said, it would be much tougher to show that it deserves to be the "cornerstone of dual antiplatelet therapy."

Indeed, there are a lot of data now that support switching HBR patients to single-antiplatelet therapy with a P2Y12 inhibitor, Robert Harrington, MD, Stanford University, California, told | Medscape Cardiology.

"What I and others do is take away the aspirin first. The key question that I'm still uncomfortable with is, how soon do you take away the aspirin?"

If, for example, the patient has atrial fibrillation and is on triple-therapy with an OAC and DAPT after stenting, then Harrington would recommend dropping the aspirin after 1 month, he said.

But, "for the routine patient, I very much individualize. Really high ischemic risk, diabetic, multivessel disease, or a lot of stents in — I will try to push the dual antiplatelet therapy longer, upward of a year. But when I take something away, if cost is not a barrier to them, I'm more likely now to peel away the aspirin."

Of the 2009 HBR patients in the trial who received at least one SYNERGY stent followed by DAPT at 110 sites around the world, Kirtane said in his formal presentation of EVOLVE Short DAPT here, 1912, or about 95%, were available for follow-up at 3 months.

Of those, 1487 had not experienced an MI or stent thrombosis during the 3 months, and so were eligible for withdrawal of the P2Y12 inhibitor. Then on aspirin only, they were followed out to 15 months. The remaining 425 patients continued on DAPT.

Of the 1032 who were not on OAC, 7.1% experienced BARC 2, 3, 5 bleeding.

Of the patients on single antiplatelet therapy, 5.8% died or experienced an MI from months 3 to 15; the rate of MI by itself was 1.9%. Also, 0.3% had "definite or probable" stent thrombosis and 1.4% experienced a stroke.

The rate of death or MI from 3 to 15 months in the single-antiplatelet group was compared, in a propensity-adjusted analysis, with the rate in a historic control group composed of patients from previous trials of DAPT sustained for 12 months after DES intervention.

The rate was 5.6% for the 1454 patients in the current study and 5.7% for their 1493 matched historic control subjects (P = .0016 for noninferiority), Kirtane reported.

In a separate propensity-adjusted comparison of EVOLVE Short DAPT patients with matched historic control subjects, the rate of BARC 1, 3, or 5 bleeding was 6.26% in 974 patients in the current study who had DAPT for only 3 months, and 4.17% in the 947 historic control subjects who had DAPT for 12 months (P = .98 for superiority).

EVOLVE Short DAPT was funded by Boston Scientific. Kirtane disclosed receiving institutional funding from Medtronic, Boston Scientific Corporation, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, and ReCor Medical. Capodanno discloses receiving honoraria or fees for speaking or consulting from AstraZeneca, Bayer AG, Daiichi-Sankyo/Eli Lilly, and Sanofi-Aventis. Ben-Yahuda and Harrington had no disclosures.

Transcatheter Cardiovascular Therapeutics (TCT) Conference 2019: Presented September 26, 2019.

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