One month of twin antiplatelet remedy (DAPT) adopted by 11 months of clopidogrel monotherapy failed to sign noninferiority to 12 unbroken months of DAPT for accept clinical revenue in a multicenter Jap trial that randomized bigger than 4000 patients who underwent percutaneous coronary intervention (PCI) after a unusual acute coronary syndrome episode.
The outcomes showed that whereas truncating DAPT duration could well, as anticipated, cut predominant bleeding episodes roughly in half, it also led to a valuable device doubling of myocardial infarction (MI) and showed a sturdy pattern in the direction of also rising a composite tally of quite rather a lot of forms of ischemic occasions. These info had been reported this week by Hirotoshi Watanabe, MD, PhD, at the digital annual congress of the European Society of Cardiology. All watch patients had gone through PCI with cobalt-chromium everolimus-eluting (CCEE) coronary stents (Xience™).
These findings from the STOPDAPT-2 ACS trial highlighted the boundaries of minimizing DAPT after PCI in patients at high ischemic chance, equivalent to after an acute coronary syndrome (ACS) match.
It also used to be a counterpoint to a considerably connected watch also reported at the congress, MASTER DAPT, which showed that 1 month of DAPT used to be noninferior to 3 or more months of DAPT for accept clinical revenue in a distinctly diverse inhabitants of patients undergoing PCI (and the utilization of a diverse form of coronary stent) — these at high bleeding chance and with most efficient about half the patients having had a unusual ACS.
The outcomes of STOPDAPT-2 ACS “enact now now not toughen use of 1 month of DAPT adopted by P2Y12 inhibitor monotherapy with clopidogrel in contrast with same old DAPT,” commented Robert A. Byrne, MBBCh, PhD, designated discussant for the document and professor at the RCSI University of Medication and Health Sciences in Dublin, Eire.
“Regardless that predominant bleeding used to be vastly reduced with this device, there seemed as if it could perhaps well be a valuable amplify in adverse ischemic occasions, and there used to be a certain signal when it comes to overall mortality, the supreme arbiter of accept clinical revenue,” added Byrne, who is also director of cardiology at Mater Private Clinic in Dublin.
He urged that a mechanistic motive of the signal of harm appear in STOPDAPT-2 ACS used to be the relatively low efficiency of clopidogrel (Plavix) as an antiplatelet agent, in contrast with diverse P2Y12 inhibitors equivalent to prasugrel (Effient) and ticagrelor (Brilinta), to boot to the genetically driven variability based completely mostly on clopidogrel that’s also absent with different agents.
These between-agent variations are of “particular clinical relevance within the early aftermath of an ACS match,” Byrne said.
12-Month DAPT Stays Identical old for PCI Sufferers With Most up-to-date ACS
The totality of clinical evidence “continues to augment a passe 12-month duration of DAPT — the utilization of aspirin and both prasugrel or ticagrelor — as basically the most in fashion default device,” Byrne concluded.
He acknowledged that an abbreviated duration of DAPT adopted by P2Y12 inhibitor monotherapy “could well very effectively be conception to be as an different.” In patients following an ACS match who enact now now not comprise high chance for bleeding, he said, the minimal duration of DAPT wish to be as a minimal 3 months and with preferential use of a stronger P2Y12 inhibitor.
Twelve months of DAPT medication with aspirin and a P2Y12 inhibitor for patients following PCI “stays the long-established of care in tricks,” famed Marco Roffi, MD, a 2nd discussant at the congress. Nonetheless quite rather a lot of questions remain, he added, equivalent to which P2Y12 inhibitors work most efficient and whether DAPT could well very effectively be lower than 12 months.
“The investigators [for STOPDAPT-2 ACS] pushed these questions to the limit with 1 month of DAPT and clopidogrel monotherapy,” said Roffi, professor and director of interventional cardiology at University Clinic, Geneva, Switzerland.
“This used to be a harmful wager, and the investigators misplaced by now now not proving noninferiority and with excess ischemic occasions,” he commented.
First Came STOPDAPT-2
Watanabe and colleagues designed STOPDAPT-2 ACS as a custom-up to their prior STOPDAPT-2 trial, which randomly assigned a minute bit bigger than 3000 patients at 90 Jap centers to the identical two medication alternate choices: 1 month of DAPT adopted by 11 months of clopidogrel monotherapy or 12 months of DAPT, aside from the trial enrolled all forms of patients undergoing PCI. This supposed that a minority, 38%, had a unusual ACS match, whereas the closing patients had chronic coronary artery disease. As in STOPDAPT-2 ACS, all patients in STOPDAPT-2 had purchased a CCEE stent.
STOPDAPT-2 also extinct the same valuable endpoint to tally accept clinical revenue as STOPDAPT-2 ACS: cardiovascular dying, MI, stroke of any type, certain stent thrombosis, or TIMI predominant or minor bleeding classification.
In STOPDAPT-2, the utilization of the blended inhabitants with each unusual ACS and chronic coronary disease, the routine of 1 month of DAPT adopted by 11 months of clopidogrel monotherapy used to be each noninferior to and superior to 12 months of DAPT, cutting back the online adverse-match tally by 36% relative to 12-month DAPT and by an absolute cut charge of 1.34%, as reported in 2019.
With out reference to this superiority, the outcomes from STOPDAPT-2 had minute influence on worldwide prepare, commented Kurt Huber, MD, professor and director of the cardiology ICU at the Medical University of Vienna, Austria.
“STOP-DAPT-2 did now now not give us a certain message with admire to cutting back antiplatelet medication after 1 month. I conception that for ACS patients 1 month could well very effectively be too short,” Huber said throughout a press briefing.
Specializing in Put up-ACS
To straight tackle this reveal, the investigators launched STOPDAPT-2 ACS, which extinct the same assemble as the preceding watch but most efficient enrolled patients rapidly after an ACS match. The trial included for its predominant prognosis 3008 newly enrolled patients with unusual ACS, and 1161 patients who had a unusual ACS match and had been randomly assigned in STOPDAPT-2, creating a entire watch cohort for the unusual prognosis of 4136 patients treated and adopted for the watch’s fat 12 months.
The patients averaged 67 years oldschool, 79% had been men, and 30% had diabetes. About 56% had a unusual ST elevation MI, about 20% a unusual non-ST elevation MI, and the closing 24% had unstable angina. For their unspecified P2Y12 inhibition, roughly half the patients purchased clopidogrel and the leisure purchased prasugrel. Adherence to the 2 assigned medication regimens used to be very factual, with a in actual fact slight selection of patients now now not adhering to their assigned protocol.
The composite adverse match incidence over 12 months used to be 3.2% among these who purchased 1-month DAPT and a pair of.83% in these on DAPT for 12 months, a distinction that failed to operate the prespecified definition of noninferiority for 1-month DAPT, reported Watanabe, an interventional coronary heart specialist at Kyoto University.
The ischemic match composite used to be 50% lower among these on 12-month DAPT in contrast with 1 month of DAPT, a distinction that correct left out significance. The charge of MI used to be 91% bigger with 1-month DAPT in contrast with 12 months, a valuable distinction.
One-month DAPT also vastly reduced the principle measure of bleeding occasions — the mix of TIMI predominant and minor bleeds — by a valuable 54% in contrast with 12-month DAPT. A 2nd metric of clinically meaningful bleeds, other folks that meet both the sort 3 or 5 definition of the Bleeding Academic Research Consortium (BARC), had been reduced by a valuable 59% by 1-month DAPT in contrast with 12 months of DAPT.
The unusual findings from STOPDAPT-2 ACS contrasted with these from MASTER DAPT, but in an explicable manner that connected to diverse patient forms, diverse P2Y12 inhibitors, diverse medication intervals, and diverse stents.
“We now comprise viewed in MASTER DAPT that when you happen to use the supreme stent and use ticagrelor for monotherapy there could well very effectively be some ability to shorten DAPT, but we restful enact now now not know what would happen in patients with very high ischemic chance,” concluded Huber.
“A cut charge in DAPT duration could well work in patients without high bleeding chance, but I would exclude patients with very high ischemic chance,” he added. “I will even now now not repeat you whether 1 month or 3 months is the supreme device, and I center of attention on clopidogrel is now now not the supreme drug to use for monotherapy after ACS.”
STOPDAPT-2 and STOPDAPT-2 ACS had been each sponsored by Abbott Vascular, which markets the cobalt-chromium everolimus-eluting (Xience) stents extinct in each analysis. Watanabe has purchased lecture costs from Abbott and from Daiichi-Sankyo. Byrne has purchased analysis funding from Abbott Vascular to boot to from Biosensors, Biotronik, and Boston Scientific. Roffi has purchased analysis funding from Biotronik, Boston Scientific, GE Healthcare, Medtronic, and Terumo. Huber has purchased lecture costs from AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Eli Lilly, Pfizer, sanofi-aventis, and The Medicines Company.
European Society of Cardiology (ESC) Congress 2021. Supplied August 30, 2021.
Mitchel L. Zoler is a reporter with Medscape and MDedge based completely mostly within the Philadelphia blueprint. @mitchelzoler