Potent P2Y12 inhibitors versus Clopidogrel in elderly patients with acute coronary syndrome: Systematic review and meta-analysis

Am Heart J. 2021 Jul:237:34-44. doi: 10.1016/j.ahj.2021.03.009. Epub 2021 Mar 15.

Abstract

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, I2 = 9%), all-cause mortality (HR: 0.89; 95% CI [0.74-1.07], P = .22, I2 = 29%), reduced the risk of cardiovascular death (HR: 0.82; 95% CI [0.68-0.98], P = .03, I2 = 16%) but increased the risk of major bleeding (HR: 1.27; 95% CI [1.04-1.56], P = .02, I2 = 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.

Keywords: Acute coronary syndrome; Clopidogrel; Elderly; P2Y12 inhibitor; Prasugrel; Ticagrelor.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Administration, Oral
  • Age Factors
  • Aged
  • Clopidogrel / administration & dosage*
  • Dose-Response Relationship, Drug
  • Humans
  • Purinergic P2Y Receptor Antagonists / administration & dosage*
  • Risk Assessment / methods*
  • Treatment Outcome

Substances

  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel