Ticagrelor may confer risk for death, bleeding in older patients with ACS vs. clopidogrel
Among patients 80 years or older, treatment of ACS with ticagrelor was associated with greater risk for death and bleeding compared with clopidogrel, researchers reported.
According to research presented at the European Society of Cardiology Congress and published in Circulation, the composite outcome of MI, stroke, death or readmission for bleeding was no different between treatment modalities.
“Ticagrelor (Brilinta, AstraZeneca), one of the most potent P2Y12 platelet inhibitors, combined with aspirin is recommended [by the ESC guidelines] for the duration of 1 year for following a myocardial infarction to reduce the risk of an ischemic event,” Karolina Szummer, MD, PhD, researcher in the department of cardiology at Karolinska Institutet in Stockholm, Sweden, said during a presentation. “This is based on the PLATO trial, which was published in 2009. Ticagrelor compared with clopidogrel reduced the risk of ischemic outcome at 12 months by 16%.
“This observational analysis from the SWEDEHEART registry indicates that ticagrelor should be used with caution among elderly patients who are 80 years and older as this medication is associated with increased risk of death and bleeding,” Szummer said during the presentation. “This an observational study with the problem of selection bias. Therefore, there is a need for adequately powered randomized studies examining the effects of proven antiplatelet [therapies] in the elderly population.”
For this analysis, investigators assessed 14,005 patients at least 80 years of age with ACS on dual antiplatelet therapy with either ticagrelor (39.8%) or clopidogrel (60.2%) plus aspirin and compared outcome between the two platelet inhibitors. The primary outcome was a composite of all-cause death, MI and stroke at 1 year. The secondary composite endpoint was all-cause death, MI, stroke and readmission for bleeding at 1 year.
Ticagrelor vs. clopidogrel in ACS
From 2010 to 2017, use of ticagrelor for ACS in patients aged 80 years or older increased more than 60%, according to the study.
Although occurrence of the primary and secondary composite endpoints was similar between the ticagrelor and clopidogrel groups (HR for primary outcome = 0.97; 95% CI, 0.88-1.06; HR for secondary outcome = 1.03; 95% CI, 0.94-1.12), investigators observed that patients on ticagrelor were more likely to die (HR = 1.17; 95% CI, 1.03-1.32) and experienced approximately 48% more readmissions for bleeding (HR = 1.48; 95% CI, 1.25-1.76) compared with patients taking clopidogrel.
However, the ticagrelor group experienced fewer MIs and strokes at 1 year (HR for MI = 0.8; 95% CI, 0.7-0.92; HR for stroke = 0.72; 95% CI, 0.56-0.92), compared with patients on clopidogrel.
Ticagrelor vs. clopidogrel in younger patients
In a secondary analysis that included 58,671 patients aged less 80 years of age who received either ticagrelor (61.8%) or clopidogrel (38.2%) for ACS, researchers found that the ticagrelor group experienced a significantly lower risk for death compared with those on clopidogrel (HR = 0.85; 95% CI, 0.76-0.96). The risk for bleeding among younger patients taking ticagrelor was elevated compared with those taking clopidogrel (HR = 1.32; 95% CI; 1.18-1.47), but not to the same degree as in older patients.
“Our results are somewhat in contrast from the PLATO trial, in which there were no signs of an age-by-treatment interaction,” Szummer and colleagues wrote in Circulation. “It is important to note that patients included in clinical trials are very different from those in real-world clinical practice. But not all elderly people are the same and several other factors influence the risk of bleeding, and high age is associated with high platelet reactivity and increased risk of thrombotic complications. Before we have more evidence from randomized trials, a more individualized approach may be appropriate in the elderly.”
Reference:
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Szummer K, et al. 1. Late-Breaking Science in Acute Coronary Syndromes 2. Presented at: European Society of Cardiology Congress; Aug. 29-Sept. 1, 2020 (virtual meeting).
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