Ticagrelor Versus Clopidogrel in Elderly Patients With Acute Coronary Syndromes: A Substudy From the Prospective Randomized PLATelet Inhibition and Patient Outcomes (PLATO) Trial

S. Husted, S. James, R. C. Becker, J. Horrow, H. Katus, R. F. Storey, C. P. Cannon, M. Heras, R. D. Lopes, J. Morais, K. W. Mahaffey, R. G. Bach (+2 others)
2012 Circulation. Cardiovascular Quality and Outcomes  
A ge is a strong predictor of adverse outcomes after acute coronary syndrome (ACS). 1-3 As a result of higher prevalence of cardiac risk factors and impaired healing processes, 4-6 elderly patients with ACS are at higher risk of recurrent ischemic events and death, as well as treatment-related complications compared with younger patients. It has been reported that patients >75 years of age comprise one third of overall ACS episodes and that this age group accounts for around 60% of the overall
more » ... ortality from ACS. 7,8 Further, after allowance for confounding factors, the odds for in-hospital death from acute events increases by 70% for each 10-year increase in age (odds ratio, 1.70; 95% confidence interval [CI], 1.52-1.82). 3 Atypical symptoms are more common in elderly patients presenting with ACS, 9 dyspnea, and confusion are relatively common, whereas ischemic pain is less likely to be present or is present in an atypical location. 7, 9 Age features as a risk factor in many bleeding risk stratification models. 10-12 Indeed, bleeding risk is greater in elderly versus younger patients; in a recent meta-analysis of stroke prevention in elderly patients with atrial fibrillation, the risk of serious bleeding increased for each decade increase of age (hazard ratio (HR), 1.61; 95% CI, 1.47-1.77 13 ). Furthermore, the use of several antiplatelet and anticoagulant therapies is associated with increased bleeding risk in the elderly with a Background-Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (≥75 years of age) with acute coronary syndrome compared with those <75 years of age. Methods and Results-The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged ≥75 years of age (n=2878) and those <75 years of age (n=15 744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged ≥75 years (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27) or patients aged <75 years (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction. Conclusions-The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872. (Circ Cardiovasc Qual Outcomes. 2012;5:680-688.)
doi:10.1161/circoutcomes.111.964395 pmid:22991347 fatcat:xxy7do2whffspkbnzub5yduohe