In aged or low-weight sufferers with acute coronary syndrome (ACS), a diminished dose of prasugrel relative to a full-dose of ticagrelor is related to decrease numerical charges of ischemic occasions and bleeding occasions, in keeping with a prespecified substudy of the ISAR-REACT 5 trial.
“The current examine supplies the strongest help for reduced-dose prasugrel as the usual for aged and low-weight sufferers with ACS present process an invasive remedy technique,” in keeping with the senior creator, Adnan Kastrati, MD, professor of cardiology and head of the Catheterization Laboratory at Deutsches Herzzentrum, Technical College of Munich.
The primary outcomes of ISAR-REACT 5, an open-label, head-to-head comparability of prasugrel and ticagrelor in sufferers with ACS, confirmed that the chance of the composite main endpoint of loss of life, myocardial infarction, or stroke 1 12 months after randomization was considerably larger for these on ticagrelor than prasugrel (hazard ratio, 1.39; P = .006). The bleeding danger on ticagrelor was additionally larger however not considerably totally different (5.4% vs. 4.8%; P = .46) (Schüpke S et al. N Engl J Med. 2019 Oct;381:1524-34).
On this substudy newly revealed in Annals of Inner Drugs, outcomes had been in contrast within the 1,099 sufferers who had been 75 years or older or weighed lower than 60 kg. On this group, in contrast to these youthful or weighing extra, sufferers had been randomized to obtain a diminished upkeep dose of 5 mg of once-daily prasugrel (moderately than 10 mg) or full dose ticagrelor (90 mg twice day by day).
At 1 12 months, the low-dose prasugrel technique relative to ticagrelor was related to a decrease charge of occasions (12.7% vs. 14.6%) and a decrease charge of bleeding (8.1% vs. 10.6%), outlined as Bleeding Tutorial Analysis Consortium (BARC) sort 3-5 occasions.
Neither the 18% discount for the efficacy endpoint (HR, 0.82; 95% CI 0.60-1.14) nor the 28% discount within the bleeding endpoint (HR, 0.72; 95% CI 0.46-1.12) reached significance, however Dr. Kastrati reported that there was a major “remedy effect-by-study-group interplay” for BARC 1-5 bleeding (P = .004) favoring prasugrel. This helps low-dose prasugrel as a method to stop the surplus bleeding danger beforehand noticed with the usual 10-mg dose of prasugrel.
In different phrases, a diminished dose of prasugrel, in contrast with the usual dose of ticagrelor, in low-weight and aged sufferers “is related to maintained anti-ischemic efficacy whereas defending these sufferers towards the surplus danger of bleeding,” he and his coinvestigators concluded.
Low-weight and older sufferers represented 27% of these enrolled in ISAR-REACT 5. When in comparison with the examine inhabitants as a complete, the chance for each ischemic and bleeding occasions was no less than twice as excessive, the authors of an accompanying editorial noticed. They praised this effort to refine the optimum antiplatelet routine in a very-high-risk ACS inhabitants.
“The present evaluation means that the prasugrel dose discount routine for aged or underweight sufferers with ACS is efficient and protected,” in keeping with the editorial coauthors, David Conen, MD, and P.J. Devereaux, MD, PhD, who’re affiliated with the Inhabitants Well being Analysis Institute, Hamilton, Ontario.
This substudy was underpowered to point out superiority for the efficacy and security outcomes in aged and low-weight ACS sufferers, which makes these outcomes “speculation producing,” however the authors imagine that they supply the perfect accessible proof for choosing antiplatelet remedy on this difficult subgroup. Though the exclusion of sufferers at very excessive danger of bleeding from ISAR-REACT 5 recommend findings won’t be related to all aged and low-weight people, the investigators imagine the information do inform medical apply.
“Our examine is the primary head-to-head randomized comparability of the diminished dose of prasugrel towards commonplace dose of ticagrelor in aged and low-weight sufferers,” mentioned Dr. Kastrati in an interview. “Particularly designed research for this subset of sufferers are not possible to be performed sooner or later.”
Dr. Kastrati reported no potential conflicts of curiosity related to this examine.
SOURCE: Menichelli M et al. Ann Intern Med. 2020 Jul 21. doi: 10.7326/M20-1806.
This story initially appeared on MDedge.com.