3 Ticagrelor is from a new class of drugs (cyclopentyl triazolo pyrimidine) that differs from thienopyridines. Since then, new P2Y 12-ADP receptor antagonists, such as ticagrelor and prasugrel, have been developed to overcome these limitations and further improve the clinical outcome of patients suffering from ACS. These limitations were associated with adverse ischemic events including stent thrombosis. In 2001, stent thrombosis continued to occur despite DAPT, leading investigators to suspect clopidogrel "resistance." In fact, biological studies showed that clopidogrel, which is a pro-drug with a short-lived active metabolite, had a mild potency, a slow onset of action, and a large inter-individual variability in its biological effects. 1 Clopidogrel remained the gold standard of P2Y 12-ADP receptor antagonists for several years and participated in the wide expansion of percutaneous coronary intervention (PCI) for revascularization. Indeed, dual antiplatelet therapy (DAPT) is mandatory to prevent patients from ischemic recurrences (including stent thrombosis, myocardial infarction, and cardiovascular death) during these acute atherothrombotic events. "Now to me it's confirmatory that you can change outcomes by inhibiting this for another year," conference chair Athena Poppas, MD, director of the echocardiography lab at Rhode Island Hospital and director of cardiovascular imaging at its Cardiovascular Institute, both in Providence.Blockade of the P2Y 12-ADP receptor is critical in the care of acute coronary syndromes (ACS). However, Weaver and others saw the findings as confirmation of the recent benefits seen with 30 months versus the typical 12 months of dual antiplatelet therapy (DAPT) after stenting in the landmark DAPT trial. He suggested that the data could prompt speculation as to whether dual platelet inhibition with high-potency agents is "approaching the point of diminishing returns." "On the basis of the 60-mg ticagrelor dose, treating 10,000 patients for 1 year would prevent approximately 42 primary endpoint events and produce approximately 31 TIMI major bleeding events - close to an even proposition," he wrote. Keaney Jr., MD, of the University of Massachusetts Medical School in Worcester, said in an accompanying editorial. The results, confirming top-line results released by drugmaker AstraZeneca in January from the 21,162-patient trial, might make a greater case for ticagrelor's use in secondary prevention but weren't seen as a home run for the drug.Įven that efficacy may really be a somewhat zero-sum game, John F. Sabatine, MD, MPH, who reported the results at a late-breaking clinical trial session at the American College of Cardiology (ACC) meeting in San Diego. The 60-mg dose is probably the better choice because it was better tolerated and caused less bleeding, said PEGASUS principle investigator Marc S. Rates of major bleeding by Thrombolysis in Myocardial Infarction (TIMI) criteria were more than doubled with ticagrelor, at 2.60% with 90-mg and 2.30% with 60-mg versus 1.06% with placebo (both P<0.001).īut the most worrisome forms - intracranial hemorrhage and fatal bleeding - were not elevated with ticagrelor. 7.77% on 60-mg ticagrelor twice daily and aspirin (hazard ratio 0.84, 95% CI 0.74 to 0.95).The primary composite of cardiovascular death, MI, or stroke at 3 years of treatment occurred in:
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