Research in context
Evidence before this study
For patients with acute coronary syndrome, European guidelines recommend potent platelet inhibition with aspirin and ticagrelor or prasugrel, irrespective of age. Therefore, older patients receive potent platelet inhibitors, despite the fact that they are at increased risk of bleeding. To identify the optimal antiplatelet regimen, we did a search in PubMed on Nov 19, 2019, with no language restrictions using the search terms “acute coronary syndrome”, “clopidogrel”, “ticagrelor” and “prasugrel”.
We found two trials that showed prasugrel (TRITON-TIMI 38 trial) and ticagrelor (PLATO trial) are superior to clopidogrel at reducing cardiovascular death and reducing myocardial infarction and stroke. TRITON-TIMI 38 did not show a net clinical benefit of prasugrel in the subgroup of older patients (aged ≥75 years), due to higher rates of bleeding, and therefore the use of prasugrel is not recommended in patients of this age, or with dose adjustment. Although, the superiority of ticagrelor in the PLATO trial was not found to be age dependent, ticagrelor related bleeding (including intracranial and fatal bleeding) occurred more frequently, especially in the older patients, than did clopidogrel related bleeding. Therefore, the preference for ticagrelor in older patients from the guideline seems controversial. The Elderly ACS 2 trial, aimed to show superiority of prasugrel 5 mg over clopidogrel in older patients with acute coronary syndrome; however, was prematurely interrupted because of futility for efficacy. After recruitment of 1443 patients, at 1-year follow-up, the primary outcome of mortality, myocardial infarction, stroke, rehospitalisation for cardiovascular causes, or bleeding occurred equal in both groups.
Added value of this study
The POPular AGE trial is the first randomised trial to investigate clopidogrel versus ticagrelor or prasugrel in patients aged 70 years or older with a non-ST-elevation acute coronary syndrome. Treatment with clopidogrel on top of standard treatment significantly reduced bleeding risk and did not increase risk of thrombotic events compared with ticagrelor or prasugrel. By showing non-inferiority of clopidogrel in net clinical benefit (all-cause death, myocardial infarction, stroke, and PLATelet inhibition and patient Outcomes; major or minor bleeding), our trial provides important evidence justifying treatment with clopidogrel as an alternative strategy in older patients with non-ST-elevation acute coronary syndrome.
Implications of all the available evidence
Popular AGE has proven the safety and efficacy of a treatment strategy with clopidogrel in older patients with non-ST-elevation acute coronary syndrome, especially when these patients have a higher bleeding risk. Therefore, clopidogrel is a favourable alternative to ticagrelor.