Safe to Drop P2Y12 Inhibitor at 3 Months in High-Bleeding-Risk Patients: EVOLVE Short DAPT

SAN FRANCISCO, CA—Elderly patients at high bleeding risk who receive Synergy everolimus-eluting stents (Boston Scientific) can, if needed, safely stop taking their P2Y12 inhibitor at 3 months and continue on aspirin alone, according to the single-arm EVOLVE Short DAPT study released today at TCT 2019.

The results come on the heels of the randomized TWILIGHT trial, published simultaneously in the New England Journal of Medicine. TWILIGHT took a different approach—dropping aspirin while retaining ticagrelor (Brilinta; AstraZeneca)—and found that the 3-month dual antiplatelet therapy (DAPT) regimen was associated with lower rates of bleeding but no increased risk of death, MI, or stroke.

EVOLVE Short DAPT investigator Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), told reporters during a press briefing that it’s important to look at trials focused on DAPT from a “historical perspective.”

Concerns over late stent thrombosis, dating back to 2006, led to guideline changes extending dual antiplatelet therapy to 1 year as a way of mitigating risk, he said. “This was largely based on observational data and not randomized data. And we know that since then, stents have become safer.” As a result, Kirtane explained, numerous trials have investigated the de-escalation of DAPT, whether by potency or duration.

Here, researchers focused their inquiry on patients who might have much to gain from earlier discontinuation of DAPT: those whose bleeding risk outweighs the potential ischemic benefits of a longer course.

EVOLVE Short DAPT

Kirtane and colleagues enrolled 2,009 patients implanted with the thin-strut, bioresorbable-polymer Synergy stent. Clinical follow-up at 3 months was available for 1,912 patients. Of those, 77.7% were free from stroke, MI, revascularization, and stent thrombosis after the 3-month DAPT regimen and thus were eligible to discontinue their P2Y12 inhibitor.

Two-thirds (67.5%) of the eligible patients were at least 75 years old and thought to have a risk of major bleeding that, after 3 months of DAPT, would outweigh the benefit of these medications; additionally, 30.6% had a need for chronic or lifelong anticoagulation (for whom aspirin was optional), 13.4% had a history of ischemic or hemorrhagic stroke, 9.1% had renal insufficiency or failure, 2.7% had a history of GUSTO major bleeding within 12 months prior to PCI, and 2.0% had a platelet count ≤ 100,000/µL. Fully 22.9% of patients met more than one of these criteria for high bleeding risk.

At 3 months, 87.3% these patients were on DAPT. By 6 months, that rate had dropped 5.2%.

In his presentation, Kirtane described the ischemic event rates as “favorable” between 3 and 15 months: 5.6% for death/MI (adjusted), 0.3% for definite/probable stent thrombosis, and 1.9% for MI alone. BARC type 2, 3, or 5 bleeding was 6.26% with 3-month DAPT and 4.17% with 12-month DAPT (P = 0.98). Using historical controls and propensity-score matching showed that 3 months of DAPT in EVOLVE was noninferior to 12 months of DAPT (P = 0.0016 for noninferiority).

“These data support the use of Synergy with a 3-month duration of DAPT in high-bleeding-risk patients,” Kirtane concluded.

Speaking with the media, Kirtane was careful to stress that 3 months of DAPT shouldn’t be a blanket approach. “What clinicians really need to know, though, is if patients have to stop, what is the safe period to potentially stop? There are many patients that have stents placed who need surgery or they have a gastrointestinal bleed and previously [based on earlier evidence] people were really struggling with this in trying to keep people on dual antiplatelet therapy up to 1 year because that’s what the guidelines had said,” he observed.

What the new data seem to indicate is that, reassuringly, 3 months of DAPT can be long enough when circumstances require a shorter duration, Kirtane added.

Kirtane emphasized that EVOLVE Short DAPT is nonrandomized and, by virtue of being observational, has the potential for unknown confounders. Moreover, the researchers had to calculate nonadjudicated events in the control group under a “worst case scenario,” censoring those whose timing was not known since these events could have happened within the first 3 months.

Following the presentation in the Main Arena, session co-moderator Magnus Ohman, MD (Duke Clinical Research Institute, Durham, NC), said that while this study involves only patients at high bleeding risk, it speaks to a larger pattern. “It tells a story that is very consistent across the board—shorter duration is better. We can talk about what you should use in that longer duration of therapy, but I think this is a very important study,” he commented.

Which Antiplatelet Should Be the ‘Single’?

Moderating the press conference, Ori Ben-Yehuda, MD (Cardiovascular Research Foundation, New York, NY), posed a hypothetical question to panelists: “You’re now in clinic and you have to make the best decision. You have a patient at high bleeding risk and you want to go to [single antiplatelet therapy]. What would [you] do?”

TWILIGHT would suggest dropping aspirin, whereas the current study supports dropping the P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel). There’s also the question of which P2Y12 inhibitor to use and when.

Answers were mixed, but several panelists noted that views on aspirin are shifting. Robert Harrington, MD (Stanford University School of Medicine, CA), for instance, said, “We’ve moved from a time where taking away aspirin was thought to be sacrilegious, because it was largely based on belief over data, to an era where we can see taking away aspirin and going with a P2Y12 inhibitor.”

This change is particularly startling given how long aspirin has been a mainstay of medicine, Vijay Kunandian, MBBS (Newcastle University, England), pointed out. “Aspirin has been around since the late 1800s, I believe.”

In her own view, Kunandian said, clopidogrel would be the best way to go, particularly in elderly patients. She pointed out that in TWILIGHT, which tested a more potent antiplatelet, the mean age was 65 years.

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