Select high bleeding risk (HBR) patients can safely receive just 1 or 3 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) without more ischemic events, according to results of the XIENCE 90 and XIENCE 28 trials.
The two single-arm trials met noninferiority for the primary endpoint of all-cause death or myocardial infarction (MI), but failed to achieve superiority for clinically relevant BARC 2-5 bleeding compared with real-world historical controls.
However, both trials reached that bar for major BARC 3-5 bleeding, with a very low incidence of stent thrombosis, Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai in New York City, reported in a late-breaking clinical science session at TCT Connect, the virtual meeting of Transcatheter Cardiovascular Therapeutics (TCT) 2020.
Recent trials on next-generation drug-eluting stents such as LEADERS-FREE SENIOR and ONYX ONE have shown an acceptable safety profile with shorter DAPT. “However, the optimal DAPT duration in high bleeding risk patients remains unknown,” she noted.
XIENCE 90 enrolled 2047 patients who underwent successful PCI with Abbott’s XIENCE everolimus-eluting stent, and were treated with aspirin plus a P2Y12 inhibitor for 3 months, followed by aspirin monotherapy in 1693 of these patients (88%) who were event free and medication compliant at 3 months. The primary analysis period was between 3 and 12 months.
Similarly, XIENCE 28 enrolled 1605 patients treated with the same stent but 1 month of DAPT, followed by aspirin alone in 1392 patients (90%) who were event free and compliant at 1 month. The primary analysis period was between 1 to 6 months.
The all-comer XIENCE V post-approval study served as the control group in propensity score matched analyses for both trials, led by Mehran and Marco Valgimigli, MD, PhD, CardioCentro Ticino, Lugano, Italy, and University of Bern, Switzerland.
Mehran observed that these patients were truly HBR, with the trials enrolling only patients who had at least one of several risk criteria (age at least 75 years, chronic or lifelong anticoagulation, a history of major bleeding within 12 months, renal insufficiency, a history of stroke, or anemia) and whose physician felt the risk of major bleeding with more than 1 month of DAPT would outweigh the benefits.
Importantly, however, she pointed out key exclusions, including patients with ST-elevation myocardial infarction, a left ventricular ejection fraction < 30%, a planned surgery within 1 or 3 months of PCI, target lesions containing thrombus or overlapping stents, target lesions in the left main coronary artery or within an arterial or saphenous vein graft, chronic total occlusions, and restenotic target lesions.
Noninferior for Ischemic Outcomes
In XIENCE 90, all-cause death or MI occurred in a mean of 5.4% of patients and 5.4% of historic controls treated with 12 months of DAPT, which met the noninferiority margin of 2.8% (P = .0063).
For XIENCE 28, the same primary endpoint occurred in a mean of 3.5% of patients and 4.3% of controls treated with 6 months of DAPT, which met the noninferiority margin of 2.5% (P = .0005).
BARC type 2-5 bleeding trended lower compared with controls but failed to meet the superiority margin in both XIENCE 90 (5.1% vs 7.0%; P = .0687) and XIENCE 28 (4.9% vs 5.9%; P = .19).
Mehran pointed out that the XIENCE V protocol, unfortunately, did not mandate collection of BARC 2 bleeding events but that superiority was met in a non-prespecified analysis of BARC 3-5 bleeding for XIENCE 90 (2.2% vs 6.3%; P < .0001) and XIENCE 28 (2.2% vs 4.5%; P = .0156).
Definite or probable stent thrombosis, a powered secondary endpoint in XIENCE 90, occurred in four patients (0.20%) between 3 and 12 months, which was significant against the performance goal of 1.2% (P <.0001).
While not a powered endpoint, rates of definite/probable stent thrombosis were identical, at 0.3%, among patients in XIENCE 28 and XIENCE V controls.
Discussant Ziad A. Ali, MD, Columbia University Medical Center/NewYork-Presbyterian Hospital in New York City, said XIENCE 90 was “really very successful and builds on the STOPDAPT-2 data.” That said, he rattled off the many exclusion criteria and questioned what’s left.
In conducting a trial like this, it’s important to first understand the safety and efficacy of the strategy, Mehran said. “I’m certain now we can start to look, hopefully, in registries in more complex patients and lesions. And, I think it’s not for everyone.”
Ali went on to ask co-study leader Valgimigli how to reconcile the current data with that showing a reduction in ischemic events with prolonged DAPT, and whether a risk score needs to be applied in every patient in clinical practice.
Valgimigli said it’s not difficult to reconcile the data because XIENCE 90/28 only focused on HBR patients, whereas trials like DAPT and PEGASUS, showing a benefit with prolonged DAPT, mainly selected low-risk patients.
“Perhaps in clinical practice, we may want to use a bleeding risk score to properly risk stratify the patient or the recently proposed HBR criteria,” he said. “Anyhow, with the data Roxana has presented, it’s only applicable to patients with high bleeding risk features, who do not derive a benefit from prolonged DAPT and, in fact, shortened DAPT is safer.”
During a press briefing on the study, discussant Allen Jeremias, MD, St. Francis Hospital, Roslyn, New York, said the XIENCE 90/28 trials are very important because HBR patients are an underserved and growing population.
“As the population ages and it’s a much more complex disease that we now treat, I think this is actually a very, very common problem,” he said. “To see that we can shorten DAPT to even 28 days is very 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.”
“The data would be different,” said Valgimigli, who observed that this hypothesis was tested in the second year of GLOBAL LEADERS. “There was some suggestion that the relative protection from ischemic endpoints was pretty much comparable,” but the bleeding risk was also alike.
The current findings with aspirin monotherapy probably also speak to the fact that “the stent platform was extremely safe” because the “stent thrombosis rate was really minimal,” he said.
The trials were sponsored by Abbott. Mehran reported relationships with several drug and device manufacturers including a consultant/advisory role with and research funding to her institution from Abbott. Valgimigli reported grant/research support from Daiichi Sankyo, Medicure, Terumo, CoreFLOW; and consulting fees/honoraria from Abbott, Alvimedica/CID, Astra Zeneca, Bayer, CoreFLOW, Chiesi, IDORSIA, Bristol Myers Squib SA, Medscape, Vesalio, and the Universität Basel Dept. Klinische Forschung.
Transcatheter Cardiovascular Therapeutics (TCT) 2020: XIENCE Short DAPT Program. Presented October 15, 2020.