Takeaway
- Early clopidogrel loading (minimum 2 hours before percutaneous coronary intervention [PCI]) is associated with better efficacy and similar bleeding risks compared with clopidogrel loading performed late in patients with ST-elevation myocardial infarction (STEMI) and non-ST elevation acute coronary syndrome (NSTE-ACS), but not in those undergoing elective PCI.
- Early loading with prasugrel and ticagrelor had no significant effects on ischaemic events.
Why this matters
- Rapid platelet inhibition is a therapeutic goal in patients with ACS undergoing PCI.
- The platelet inhibitory action of P2Y12 inhibitors is time-dependent, hence the timing of their administration is a crucial variable influencing patient outcomes.
- Yet, optimal timing of P2Y12 inhibitor loading in patients undergoing PCI remains debatable.
Study design
- Meta-analysis of 23 studies (10 randomised controlled trials [RCTs], 4 post hoc analyses of RCTs and 9 non-randomised studies) with a total of 60,907 patients.
- Primary outcomes included major adverse cardiovascular events (MACEs), myocardial infarction (MI), target vessel revascularisation (TVR), mortality and bleeding complications.
- Funding: None
Key results
- Early P2Y12 inhibitor loading was associated with a 22% relative risk reduction (RRR) of MACE (relative risk [RR], 0.78; 95% CI, 0.68–0.89; P<0.001), 30% RRR of MI (RR, 0.70; 95% CI, 0.6–0.82; P<.0001), and 25% RRR of death (RR, 0.75; 95% CI, 0.64–0.87; P=.0002).
- Rates of major bleeding events did not differ significantly between the early and late clopidogrel loading groups; 2.2% vs 1.6% (RR, 0.98; 95% CI, 0.79–1.21; P=.82).
- In the sub-group analysis, early clopidogrel loading was associated with 35% and 22% RRR of 30 days MACE in the STEMI and NSTE-ACS groups (P<.001 for both), respectively.
- Similarly, early clopidogrel loading was associated with a 39% (P<.001) and 31% (P=.0003) RRR of MI in the STEMI and NSTE-ACS groups, respectively.
- Pre-treatment with ticagrelor or prasugrel neither reduced the RR of MACE, MI, TVR, and death, nor increased major bleeding events during 30-day follow-up (P>.05).
- Early clopidogrel loading in patients undergoing elective PCI did not alter the risk for MACE, MI, TVR or bleeding events (P>.05).
Limitations
- Some included retrospective studies are more likely to have a bias (selection, observer or publication) and confounding.
- Studies have variations in the definition of MACE and classification of major bleedings.
- Significant heterogeneity among studies investigating the risk of MACE and MI.
References
References
