Shorter DAPT Succeeds in Xience-Treated Patients at High Bleeding Risk

Two large but nonrandomized studies presented today at TCT Connect 2020 solidify the case that, with current-generation DES, dual antiplatelet therapy (DAPT) can safely be shortened to just 1 or 3 months among patients at high risk for bleeding.

“DAPT is essential to prevent ischemic events after PCI but of course it increases bleeding, especially in those patients at high bleeding risk that can constitute up to 40% of patients who come to our cath labs and undergo PCI,” investigator Roxana Mehran, MD (Icahn School of Medicine at Mount Sinai, New York, NY), told the media yesterday.

“As hemorrhagic events after PCI receive a lot of attention because they have substantial prognostic implications, we are looking at bleeding-avoidance strategies to improve patient outcomes,” she continued.

One such strategy is shortened DAPT, which Mehran pointed out has demonstrated safety in the Onyx ONE, SENIOR, LEADERS FREE, and ZEUS trials. “But the optimal duration remains unclear,” she added.

XIENCE Short DAPT Program

The XIENCE Short DAPT program, led by Mehran and Marco Valgimigli, MD, PhD (Cardiocentro Ticino, Lugano, Switzerland), tested durations of 1 month and 3 months among approximately 3,600 patients. XIENCE 90, with 3-month DAPT, has enrolled 2,047 patients at 101 US sites. XIENCE 28, with 1-month DAPT, includes 963 patients at 52 global sites and 642 patients at 58 US sites. Each of the two studies is prospective, open-label, and nonrandomized.

All participants were deemed to have high bleeding risk based on whether they had at least one risk factor (age ≥ 75 years, chronic or lifelong anticoagulation, history of major bleeding ≤ 12 months of index PCI, history of stroke, renal insufficiency or failure, systemic conditions like hematological or coagulation disorders linked to bleeding, and/or anemia), or if their referring physician thought their major bleeding risk with more than 1 month of DAPT would outweigh the benefit. Patients with STEMI and those with LVEF < 30% were excluded, as were people slated to undergo surgery in the next few months.

After the index PCI with Xience DES, patients initially received a P2Y12 inhibitor plus aspirin. Then, if they were event free at 1 or 3 months, depending on the study, they continued on aspirin alone—patients had to have been free from MI, repeat revascularization, stroke, or stent thrombosis and compliant with DAPT, Mehran explained.

For XIENCE 28, the primary analysis period was between months 1 and 6. For XIENCE 90, outcomes were analyzed between months 3 and 12.

Historical controls were drawn from the XIENCE V all-comers study, published in 2012, in which 90.5% of patients were on DAPT at 6 months and 85.6% at 1 year. To test noninferiority, the researchers used the Farrington-Manning method, stratifying patients by propensity score across quintiles.

Using this method, XIENCE 90 participants had similar rates of all death or MI between 3 and 12 months compared with controls (5.4% vs 5.4%; P for noninferiority = 0.0063). XIENCE 28 also matched controls for death/MI in the test group between 1 and 6 months (3.5% vs 4.3%, P for noninferiority = 0.0005).

For the secondary endpoint of BARC type 2 to 5 bleeding, rates were 5.1% with 3-month DAPT and 7.0% among controls (P for superiority = 0.0687). Patients in XIENCE 28 on 1-month DAPT had a BARC type 2 to 5 bleeding rate of 4.9% compared to 5.9% among controls (P for superiority = 0.19). Major bleeding (BARC type 3 to 5) was less common in both XIENCE 90 (2.2% vs 6.3%, P for superiority < 0.0001) and XIENCE 28 (2.2% vs 4.5%, P for superiority = 0.0156) than in the XIENCE V cohort.

And finally, in XIENCE 90, ARC-defined definite/probable stent thrombosis occurred at a rate of 0.20% between 3 and 12 months. In both XIENCE 28 and XIENCE V, the rate was 0.3% between 1 and 6 months.

An ‘Underserved Population’

Allen Jeremias, MD (St. Francis Hospital, Rosalyn, NY), speaking at the press conference, observed that patients at high bleeding risk are an “underserved population.”

“Those are very difficult patients to treat, as we all know, so to have more-dedicated therapies available for them is very, very important, in particular because this is, I think, also a growing population. As the population ages and it’s much more complex disease that we now treat, this is actually a common problem,” he commented. “To see that we can shorten DAPT to even 28 days is good news for these patients and the outcomes are impressive—certainly there is no signal that there is a safety concern at all. And I think there is very convincing evidence that bleeding is reduced, which obviously makes intuitive sense.”

Jeremias asked what would happen if the tables were flipped, with patients continuing on P2Y12 inhibitors alone rather than aspirin monotherapy.

GLOBAL LEADERS looked at this concept, Valgimigli pointed out. “In that study, there was some suggestion that the relative protection against ischemic endpoints was pretty much comparable,” but so too was bleeding risk. Mehran said this is an important question, one that also needs to be tested in complex patients, with the goal of reducing ischemic events as well as bleeding.

Here, in XIENCE 90/28, “we were able to show this kind of a benefit with a stent platform that I think is very hard to beat,” Mehran concluded.