Clopidogrel Based Strategies in ACS

Selective, clopidogrel-based strategies vs conventional treatment in acute coronary syndrome: A study-level meta-analysis.

The approach of “unguided de-escalation” rather than “guided de-escalation” to clopidogrel resulted in reduction of major or minor bleeding complications and net clinical endpoint vs ticagrelor/prasugrel use, while sustaining similar ischemic protection in patients with ACS undergoing PCI.

Key Takeaway

• This meta-analysis of six randomized trials (RCTs) including patients with ACS undergoing PCI demonstrated:
• Incidence of major bleeding and major adverse cardiovascular events (MACE) was similar in the selective, clopidogrel-based (unguided de-escalation/guided therapy) vs conventional treatment (ticagrelor/prasugrel) approaches
• Rates of major or minor bleeding and occurrence of net clinical endpoint were lower in the selective, clopidogrel-based vs conventional treatment group
• A “plain de-escalation to clopidogrel” after PCI for ACS (driven by clinical judgment), provided a better net clinical benefit vs conventional approach when conducted approximately four weeks after the procedure
• Study findings do not support the strategy of platelet function- or genotype-guided clopidogrel therapy after PCI for patients with ACS, owing to lack of safety benefits vs conventional treatment, costs, and organizational issues

Why This Matters

• Prasugrel or ticagrelor is recommended after ACS, owing to their potent platelet inhibition and higher protection of ischemic events vs clopidogrel
  • However, this greater efficacy of potent platelet inhibition occurs at the price of increased bleeding complications.
  • Hence, two strategies with clopidogrel therapy (unguided de-escalation and guided clopidogrel therapy) have been recently developed to maintain an adequate anti-ischemic effect and reduced bleeding risk.

Study Design

• This study-level meta-analysis evaluated six RCTs investigating selective clopidogrel-based therapies vs conventional treatment with ticagrelor/prasugrel after PCI.
• Inclusion criteria: Only RCTs* enrolling ≥40% of patients with ACS
• Main safety endpoint: Pooled incidence of major bleeding
• Main efficacy endpoint: Cumulative incidence of MACE (composite of cardiovascular death, myocardial infarction, and stroke)
• Other outcome measures: Net clinical endpoint, major or minor bleeding, individual components of the MACE endpoint, stent thrombosis, and unplanned coronary revascularization

Key Results

• Meta-analysis included six RCTs (three on unguided de-escalation [N = 3,473]; three on guided clopidogrel therapy [N = 7,533])
• Overall mean duration of follow-up = 10.3 months

Safety Outcomes

• Rate of major bleeding (clopidogrel-based vs conventional therapy): 1.8% vs 3.1% (odds ratio [OR] = 0.72 [95% confidence interval {CI}: 0.51–1.01; P = 0.06])
• Rate of major or minor bleeding (clopidogrel-based vs conventional therapy): 4.8% vs 9.1% (OR = 0.57 [95% CI: 0.40–0.80; P = 0.001])
  • Greater safety of selective, clopidogrel-based therapy was significant for unguided de-escalation (4.2% vs 8.9% [OR = 0.43 {95% CI: 0.32–0.58; P <0.00001}]), and nonsignificant with guided therapy (5.2% vs 9.2 % [OR = 0.72 {95% CI: 0.51–1.02; P = 0.07}]) (P for interaction = 0.03)

Efficacy Outcomes

• Incidence of MACE: Similar for clopidogrel-based vs conventional therapy (2.9% vs 3.2% [OR = 0.93 {95% CI: 0.72–1.20; P = 0.58}])
• Net clinical endpoint (clopidogrel-based vs conventional therapy): Occurred in 6.4% vs 9.8% patients (OR = 0.59 [95% CI: 0.41–0.85; P = 0.004])
  • Statistically significant reduction for unguided de-escalation (6.1% vs 11.3% [OR = 0.50 {95% CI: 0.39–0.64; P <0.00001}]); whereas no difference was noted for guided clopidogrel and conventional therapy (6.9% vs 8.4% [OR = 0.85 {95% CI: 0.62–1.16; P = 0.30}]) (P _{for interaction} = 0.01)
• Rate of stent thrombosis: Similar for clopidogrel-based vs conventional therapy (0.50% vs 0.26% [OR = 1.60 {95% CI: 0.72–3.54; P = 0.24}])
• Unplanned coronary revascularization (reported only in three trials on unguided de-escalation vs conventional therapy): 3.5% vs 4.0% (OR = 0.86 [95% CI: 0.60–1.23; P = 0.42])

Limitations

• Absence of patient-level data hampers specific outcome analyses and prevents adjustments for differences between the included trials
• Two studies of this meta-analysis included a certain number of patients with chronic coronary syndrome
• A subpopulation was selected from the intention-to-treat overall sample in two trials to specifically address the aims of the meta-analysis
• Safety outcomes were variable across different investigations
• Number of patients was smaller in the studies on unguided vs guided therapy
• This analysis did not allow a direct comparison of unguided de-escalation vs guided clopidogrel therapy

*Please refer source publication (Patti et al.) for details on search strategy, trial characteristics, and de-escalation/platelet function testing/genotype guided approaches.

MAT-BH-2300020/V1/JAN2023