Ticagrelor for ACS confers similar net events but more bleeding, dyspnea vs. clopidogrel
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For patients with ACS, ticagrelor after PCI demonstrated similar rates of net adverse clinical events at 1 year compared with clopidogrel, according to findings published in JAMA.
However, in the retrospective, propensity-matched study, ticagrelor (Brilinta, AstraZeneca) was associated with more frequent hemorrhagic events and dyspnea compared with clopidogrel.
“In the PLATO trial, the benefit was not evident in patients from North America and Asia. Other concerns about the safety of ticagrelor include the drug-induced dyspnea and higher hemorrhagic events associated with its use, which can lead to early discontinuation,” Seng Chan You, MD, MS, of the department of biomedical informatics at the Ajou University School of Medicine in Suwon, South Korea, and colleagues wrote. “Recent observational studies have raised questions about whether ticagrelor is associated with better outcomes compared with clopidogrel in clinical practice.”
For this retrospective analysis, investigators included 31,290 matched pairs (median age group, 60 to 64 years; 29% women) of patients with ACS who underwent PCI and received either ticagrelor or clopidogrel. In addition, 95.5% of the cohort took aspirin.
The composite primary endpoint was net adverse clinical events at 12 months, which included ischemic events (recurrent MI, revascularization or stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding).
Clinical events at 1 year
Investigators found that the risk for net adverse clinical events at 12 months was no different between the ticagrelor and clopidogrel groups (15.1% vs. 14.6%, respectively; HR = 1.05; 95% CI, 1-1.1; P = .06).
There was also no difference in risk for all-cause mortality between the ticagrelor and clopidogrel groups (2% vs 2.1%, respectively; HR = 0.97; 95% CI, 0.81-1.16) or ischemic events (13.5% vs. 13.4%, respectively; HR = 1.03; 95% CI, 0.98-1.08).
“There are several possible explanations for the lack of a significant difference in risk of net adverse clinical events for patients treated with ticagrelor compared with clopidogrel,” the researchers wrote. “Owing to the observational nature of the study, residual confounding might have produced this finding. However, this study performed empirical calibration using falsification endpoints to measure and reduce the degree of systematic error, which demonstrated the low degree of residual bias.”
Hemorrhagic events, dyspnea
However, those who received ticagrelor compared had elevated risk for hemorrhagic events (2.1% vs. 1.6%; HR = 1.35; 95% CI, 1.13-1.61) and dyspnea (27.3% vs. 22.6%; HR = 1.21; 95% CI, 1.17-1.26) compared with those who received clopidogrel.
“The drug adherence in the ticagrelor group was lower than in the clopidogrel group. Nonadherence with the use of antiplatelet agents is a well-known factor associated with higher incidences of all-cause mortality, cardiovascular mortality, acute MI, unplanned revascularization, and even hemorrhagic events,” the researchers wrote. “Low adherence with ticagrelor, compared with other agents, has been consistently reported in recent randomized clinical trials, mostly because of nonserious adverse events such as dyspnea or nonmajor bleeding.
“The overall improvement in the clinical outcomes of patients with coronary diseases may be another possible explanation for the diminished benefit of ticagrelor in the modern era; in particular, this may be driven by progress in the use of drug-eluting stents and poststenting care,” the researchers wrote. “In addition, it may be that despite the finding from a single trial, ticagrelor is not more effective than clopidogrel.”
In a related editorial, Eric R. Bates, MD, professor of interventional cardiology at the University of Michigan in Ann Arbor, wrote: “Compared with clopidogrel and prasugrel (Effient, Daiichi Sankyo/Eli Lilly), ticagrelor may not demonstrate greater clinical benefit because of adverse effects (dyspnea), inconvenience (twice-daily dosing), or higher cost (clopidogrel and prasugrel are generics), which may decrease medication adherence. The pragmatic clinical recommendation, yet to be proven in randomized trials, may be to prescribe ticagrelor (or prasugrel because it was more effective than ticagrelor in one randomized trial) for patients with ACS, if the patient tolerates and can afford this medication, and to consider de-escalating to clopidogrel at 1 month after the greatest ischemic risk period has passed to decrease subsequent bleeding risk and cost.”
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