Potent P2Y12 Inhibitors Versus Clopidogrel in Elderly Patients with Acute Coronary Syndrome: Systematic Review and Meta-analysis

Background: Potent P2Y12 inhibitors reduce cardiovascular events but increase bleeding in patients presenting with acute coronary syndrome (ACS). Elderly patients are at increased risk of bleeding and whether the benefit-risk ratio of potent P2Y12 inhibitors remains favorable is not known.

Objectives: To investigate the efficacy and safety of potent P2Y12 inhibitors versus clopidogrel in elderly patients with ACS.

Methods: PUBMED and EMBASE were searched through July 2020 for randomized control trials (RCTs) or subgroup analyses of RCTs investigating potent P2Y12 inhibitors (prasugrel or ticagrelor) or clopidogrel in elderly (age ≥ 65 years) patients with ACS. The primary outcome was major adverse cardiovascular events (MACE).

Results: Our search identified 9 RCTs with a total of 10,792 elderly patients. When compared with clopidogrel, potent P2Y12 inhibitors had similar risk of MACE (hazard ratio (HR): 0.94; 95%; confidence interval (CI) [0.85-1.06], P = .31, I = 9%), all-cause mortality (HR: 0.89; 95% CI [0.74-1.07], P = .22, I = 29%), reduced the risk of cardiovascular death (HR: 0.82; 95% CI [0.68-0.98], P = .03, I = 16%) but increased the risk of major bleeding (HR: 1.27; 95% CI [1.04-1.56], P = .02, I = 0%). In a subgroup analysis, ticagrelor reduced all-cause mortality (HR: 0.73; 95% CI [0.55-0.98]) and cardiovascular death (HR: 0.70; 95% CI [0.54-0.90]) compared with clopidogrel.

Conclusions: Among elderly patients with ACS, potent P2Y12 inhibitors reduce cardiovascular death but increase bleeding with no difference in MACE or all-cause death when compared with clopidogrel. Further RCTs are needed to refine P2Y12 inhibitor selection for elderly patients with ACS.