Potent P2Y12 Inhibitors vs Clopidogrel in elderly ACS patients

Efficacy and safety of potent P2Y12 inhibitors versus clopidogrel in elderly patients with Acute Coronary Syndrome.

The results of this systematic review and meta-analysis showed that among elderly patients with Acute Coronary Syndrome (ACS), use of potent P2Y12 inhibitors reduced cardiovascular death and increased bleeding with no significant difference in major adverse cardiovascular events (MACE) or all-cause death compared to the use of clopidogrel.

Key Takeaway

• The findings of this systematic review and meta-analysis on the efficacy and safety of various P2Y12 inhibitors in elderly patients with ACS are as below:
  • Potent P2Y12 inhibitors were associated with reduced risk of cardiovascular death compared to clopidogrel.
  • Differences in MACE were not significant between patients receiving potent P2Y12 inhibitors versus clopidogrel.
  • Risk of major bleeding was significantly higher in patients receiving potent P2Y12 inhibitors vs clopidogrel.
  • In sensitivity analysis, ticagrelor significantly reduced the risk of all-cause mortality and cardiovascular death compared with clopidogrel.

Why This Matters

• Potent P2Y12 inhibitors reduce the incidence of cardiovascular disease but increase the risk of bleeding in patients with ACS.
• Although the impact of potent P2Y12 inhibitors in elderly patients with ACS has been investigated, it has not been completely elucidated.
• This study determines the efficacy and safety of potent P2Y12 inhibitors versus clopidogrel in elderly patients with ACS.

Study Design

• This systematic review and meta-analysis of randomized controlled trials (RCTs) or subgroup analyses of RCTs investigated the effect of P2Y12 inhibitors in elderly patients with ACS.
• Search strategy: 2-level search strategy (PUBMED and EMBASE) through July 2020
• Data were collected according to PICOS model:
  • Population: Patients with ACS; Interventions: P2Y12 inhibitors (prasugrel and ticagrelor); Comparison: Clopidogrel; Outcome: All-cause mortality, cardiovascular mortality, myocardial injury, stroke, major bleeding, and stent thrombosis; Study type: RCTs
• Inclusion criteria: (1) Studies published in peer-reviewed journals, (2) RCTs or subgroup analyses of RCTs enrolling patients aged ≥65 years with ACS receiving at least two P2Y12 inhibitors, (3) studies reporting outcomes of interest
• Primary outcome: MACE
• Secondary outcomes: All-cause mortality, cardiovascular death, myocardial infarction, stroke, stent thrombosis, and trial-defined major bleeding

Key Results

• Overall, 9 RCTs were identified (enrolling 10,792 elderly patients; median age: 77–80 years). Median follow-up was 12 months.
• Seven studies were identified for the direct comparison of potent P2Y12 inhibitors versus clopidogrel, and all 9 were included in the network meta-analysis.
• Compared to clopidogrel, potent P2Y12 inhibitors did not significantly decrease MACE (hazard ratio [HR] = 0.94; 95% confidence interval [CI]: 0.85–1.06, P = 0.31; no significant heterogeneity [I² = 9%, P = 0.36]).
• Differences in all-cause mortality (HR = 0.89; 95% CI: 0.74–1.07, P = 0.22, I² = 29%), myocardial infarction, stroke, and stent thrombosis were not significant between potent P2Y12 inhibitors and clopidogrel.
• Use of P2Y12 inhibitors reduced the risk of cardiovascular death compared to clopidogrel (HR = 0.82; 95% CI: 0.68–0.98, P = 0.03, I² = 16%) but increased the risk of major bleeding (HR = 1.27; 95% CI: 1.04–1.56, P = 0.02, I² = 0%).
• Network meta-analysis: Compared to clopidogrel, ticagrelor significantly 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).
  • Risk of these outcomes was not significantly different between prasugrel versus clopidogrel groups and ticagrelor versus prasugrel groups.
  • The risk of major bleeding was higher with ticagrelor and prasugrel than with clopidogrel, but without statistical significance.

Limitations

• This study is a meta-analysis of trial-level data. Therefore, differences in trial design, treatment regimens compared, and individual patient data were not considered.
• Study had limited data to assess differences within P2Y12 inhibitor groups.
• Doses of medication used or compliance to each treatment strategy was not accounted for.
• Heterogeneity was observed in the definition of endpoints (MACE and bleeding events) and age for the elderly.

MAT-BH-2300007/V1/Jan2023