Choose excessive bleeding threat (HBR) sufferers can safely obtain simply 1 or 3 months of twin antiplatelet remedy (DAPT) after percutaneous coronary intervention (PCI) with out extra ischemic occasions, in line with outcomes of the XIENCE 90 and XIENCE 28 trials.
The 2 single-arm trials met noninferiority for the first endpoint of all-cause demise or myocardial infarction (MI), however failed to attain superiority for clinically related BARC 2-5 bleeding in contrast with real-world historic controls.
Nonetheless, each trials reached that bar for main BARC 3-5 bleeding, with a really low incidence of stent thrombosis, Roxana Mehran, MD, Icahn Faculty of Drugs at Mount Sinai in New York Metropolis, reported in a late-breaking scientific science session at TCT Join, the digital assembly of Transcatheter Cardiovascular Therapeutics (TCT) 2020.
Latest trials on next-generation drug-eluting stents equivalent to LEADERS-FREE SENIOR and ONYX ONE have proven a suitable security profile with shorter DAPT. “Nonetheless, the optimum DAPT period in excessive bleeding threat sufferers stays unknown,” she famous.
XIENCE 90 enrolled 2047 sufferers who underwent profitable PCI with Abbott’s XIENCE everolimus-eluting stent, and have been handled with aspirin plus a P2Y12 inhibitor for 3 months, adopted by aspirin monotherapy in 1693 of those sufferers (88%) who have been occasion free and medicine compliant at 3 months. The first evaluation interval was between 3 and 12 months.
Equally, XIENCE 28 enrolled 1605 sufferers handled with the identical stent however 1 month of DAPT, adopted by aspirin alone in 1392 sufferers (90%) who have been occasion free and compliant at 1 month. The first evaluation interval was between 1 to six months.
The all-comer XIENCE V post-approval research served because the management group in propensity rating matched analyses for each trials, led by Mehran and Marco Valgimigli, MD, PhD, CardioCentro Ticino, Lugano, Italy, and College of Bern, Switzerland.
Mehran noticed that these sufferers have been actually HBR, with the trials enrolling solely sufferers who had not less than one in every of a number of threat standards (age not less than 75 years, power or lifelong anticoagulation, a historical past of main bleeding inside 12 months, renal insufficiency, a historical past of stroke, or anemia) and whose doctor felt the chance of main bleeding with greater than 1 month of DAPT would outweigh the advantages.
Importantly, nonetheless, she identified key exclusions, together with sufferers with ST-elevation myocardial infarction, a left ventricular ejection fraction < 30%, a deliberate surgical procedure inside 1 or 3 months of PCI, goal lesions containing thrombus or overlapping stents, goal lesions within the left important coronary artery or inside an arterial or saphenous vein graft, power whole occlusions, and restenotic goal lesions.
Noninferior for Ischemic Outcomes
In XIENCE 90, all-cause demise or MI occurred in a imply of 5.4% of sufferers and 5.4% of historic controls handled with 12 months of DAPT, which met the noninferiority margin of two.8% (P = .0063).
For XIENCE 28, the identical major endpoint occurred in a imply of three.5% of sufferers and 4.3% of controls handled with 6 months of DAPT, which met the noninferiority margin of two.5% (P = .0005).
BARC kind 2-5 bleeding trended decrease in contrast with controls however failed to satisfy the prevalence margin in each XIENCE 90 (5.1% vs 7.0%; P = .0687) and XIENCE 28 (4.9% vs 5.9%; P = .19).
Mehran identified that the XIENCE V protocol, sadly, didn’t mandate assortment of BARC 2 bleeding occasions however that superiority was met in a non-prespecified evaluation 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).
Particular or possible stent thrombosis, a powered secondary endpoint in XIENCE 90, occurred in 4 sufferers (0.20%) between 3 and 12 months, which was important towards the efficiency purpose of 1.2% (P <.0001).
Whereas not a powered endpoint, charges of particular/possible stent thrombosis have been an identical, at 0.3%, amongst sufferers in XIENCE 28 and XIENCE V controls.
Discussant Ziad A. Ali, MD, Columbia College Medical Middle/NewYork-Presbyterian Hospital in New York Metropolis, stated XIENCE 90 was “actually very profitable and builds on the STOPDAPT-2 knowledge.” That stated, he rattled off the various exclusion standards and questioned what’s left.
In conducting a trial like this, it is vital to first perceive the protection and efficacy of the technique, Mehran stated. “I am sure now we will begin to look, hopefully, in registries in additional complicated sufferers and lesions. And, I feel it isn’t for everybody.”
Ali went on to ask co-study chief Valgimigli tips on how to reconcile the present knowledge with that displaying a discount in ischemic occasions with extended DAPT, and whether or not a threat rating must be utilized in each affected person in scientific observe.
Valgimigli stated it isn’t troublesome to reconcile the information as a result of XIENCE 90/28 solely centered on HBR sufferers, whereas trials like DAPT and PEGASUS, displaying a profit with extended DAPT, primarily chosen low-risk sufferers.
“Maybe in scientific observe, we might wish to use a bleeding threat rating to correctly threat stratify the affected person or the lately proposed HBR criteria,” he stated. “Anyhow, with the information Roxana has introduced, it is solely relevant to sufferers with excessive bleeding threat options, who don’t derive a profit from extended DAPT and, the truth is, shortened DAPT is safer.”
Throughout a press briefing on the research, discussant Allen Jeremias, MD, St. Francis Hospital, Roslyn, New York, stated the XIENCE 90/28 trials are crucial as a result of HBR sufferers are an underserved and rising inhabitants.
“Because the inhabitants ages and it is a way more complicated illness that we now deal with, I feel that is really a really, quite common drawback,” he stated. “To see that we will shorten DAPT to even 28 days is excellent information for these sufferers and the outcomes are spectacular. Definitely there isn’t a sign that there’s a security concern in any respect, and I feel there’s very convincing proof that bleeding is diminished, which clearly makes intuitive sense.”
Jeremias requested the investigators whether or not sufferers would do higher if aspirin have been stopped and sufferers have been maintained on a single P2Y12 inhibitor like ticagrelor or clopidogrel.
“The information could be completely different,” stated Valgimigli, who noticed that this speculation was examined within the second 12 months of GLOBAL LEADERS. “There was some suggestion that the relative safety from ischemic endpoints was just about comparable,” however the bleeding threat was additionally alike.
The present findings with aspirin monotherapy most likely additionally communicate to the truth that “the stent platform was extraordinarily protected” as a result of the “stent thrombosis price was actually minimal,” he stated.
The trials have been sponsored by Abbott. Mehran reported relationships with a number of drug and machine producers together with a marketing consultant/advisory position with and analysis funding to her establishment from Abbott. Valgimigli reported grant/analysis help from Daiichi Sankyo, Medicure, Terumo, CoreFLOW; and consulting charges/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. Introduced October 15, 2020.