Ticagrelor failed to the United States clopidogrel because the tenet-on the spot P2Y12 inhibitor of preference in patients undergoing non-mandatory percutaneous coronary intervention for stable CAD in the randomized ALPHEUS trial.
“The greater stage of platelet inhibition obtained with ticagrelor would not translate correct into a reduction of periprocedural MI or myocardial injury interior 48 hours of excessive-pain PCI performed in stable coronary patients,” reported Johanne Silvain, MD, PhD, professor of cardiology on the Sorbonne University and director of the ICU at Pitie-Salpetriere Scientific institution, Paris, on the digital American Coronary heart Association scientific classes.
Ticagrelor did, alternatively, result in a drastically greater fee of nuisance or minor bleeding than clopidogrel interior 30 days submit PCI, moreover to extra frequent dyspnea and therapy discontinuation.
ALPHEUS became as soon as an birth-mark, randomized trial together with 1,883 patients undergoing non-mandatory PCI for stable coronary disease at 49 French or Czech PCI centers. All participants were both troponin-adverse or had a modestly elevated nonetheless declining excessive-sensitivity troponin stage. They possessed a median of 3.2 blueprint-linked or patient-linked excessive-pain facets, amongst the most general of which were multivessel disease, lengthy lesions requiring quite loads of stents, and diabetes. Sufferers were randomized to a 300- or 600-mg loading dose of clopidogrel (Kengreal) or 180 mg of ticagrelor (Brilinta) sooner than PCI. Afterwards they endured on 90 mg of ticagrelor twice daily or 75 mg of clopidogrel as soon as daily for 30 days. Everybody became as soon as additionally on aspirin.
Myonecrosis Hypothesis Falls Flat
The most main endpoint became as soon as the occurrence of most main myocardial injury, defined as a periprocedural troponin elevated greater than 5 cases the upper limit of neatly-liked interior 48 hours of PCI; form 4a MI, defined as most main myocardial injury plus signs or signs of ischemia; or stent thrombosis.
The rates were closely identical: 35.5% with ticagrelor, 36.2% with clopidogrel. The majority of events consisted of most main myocardial injury, with an incidence of 26.7% in the ticagrelor team and 27.7% with clopidogrel. Stent thrombosis occurred in 0.3% of patients in every team. Model 4a MI occurred in 8.5% of the ticagrelor team and 8.2% of patients on clopidogrel.
The gaze hypothesis became as soon as that a gargantuan fragment of periprocedural myonecrosis may per chance perhaps be thrombotic in nature, and that a stronger P2Y12 inhibitor may per chance perhaps also minimize the occurrence of these mini-infarcts and thus present patient earnings. However the hypothesis became as soon as now not borne out.
“We invent now not know if these events are a pain factor or factual a marker of pain,” Dr. Silvain talked about.
There were no between-team variations in most main bleeding events at 48 hours or 30 days. Nonetheless, the velocity of nuisance or minor bleeding at 30 days became as soon as 11.2% in the ticagrelor arm, drastically greater than the 7.5% incidence with clopidogrel. Moreover, dyspnea occurred in 11.2% of patients on ticagrelor, when put next to 0.2% with clopidogrel. Deem drug discontinuation became as soon as extra frequent in the ticagrelor arm: 2.2%, versus 0.4%.
Dr. Silvain additionally offered a pooled prognosis of the 1,883 patients in ALPHEUS plus 781 from the similarly designed SASSICAIA trial, which when put next prasugrel (Effient) to clopidogrel. Neither of the extra potent P2Y12 inhibitors showed superiority over clopidogrel.
Discussant Stephen D. Wiviott, MD, summed things up: “With out a evidence for ischemic earnings and greater rates of low-severity bleeding, this trial would not toughen the usage of extra potent P2Y12 antagonists for non-mandatory PCI. Based entirely totally on these outcomes, and in step with SASSICAIA, aspirin with clopidogrel must easy remain the favorite of care on this population.”
Troponin Response May perhaps well Fluctuate
A striking finding in ALPHEUS became as soon as the discrepancy between very excessive rates of periprocedural troponin elevation and in actuality low rates of clinical events thru 30 days of prepare-up. “When you compare at these modest elevations of troponin it appears that there is a quantity of noise right here,” talked about Dr. Wiviott, vice president for clinical trials study and administration at Massachusetts Fundamental Scientific institution and Brigham and Females’s Scientific institution and a cardiologist at Harvard Scientific College, Boston.
Troponin elevations in stable coronary patients undergoing PCI may per chance perhaps even contain a definite underlying mechanism than elevated troponins in patients undergoing PCI for an acute coronary syndrome, he added. In stable CAD patients, the phenomenon may per chance perhaps be extra linked to atherosclerosis than to platelet activation and thrombosis.
All the method thru a panel discussion, Sunil V. Rao, MD, talked about cardiologists are “potentially going to pray to head abet to the draw planning stage and knowing what kinds of events are in actuality, in actuality main.”
“It be incumbent on our profession to resolve out whether periprocedural MI must easy continue to be a ingredient of the composite endpoint in PCI trials, because it be highly relying on the definition that is being prone,” observed Dr. Rao, professor of medication at Duke University, Durham, N.C.
Dr. Silvain reported receiving institutional study funding and consulting charges from AstraZeneca, which funded the ALPHEUS trial. He serves as a expert to a handful of diversified pharmaceutical corporations as effectively.
Simultaneously with Dr. Silvain’s presentation at AHA 2020, the ALPHEUS outcomes were printed online in The Lancet.
SOURCE: Silvain J. AHA 2020. Session LBS 3
This article originally seemed on MDedge.com, phase of the Medscape Professional Community.
