Genotype-guided P2Y12 inhibitor de-escalation reduced BARC 2, 3, or 5 bleeding (HR 0.77; 95% CI 0.62-0.97) and NACE without increasing MACE compared with conventional therapy.
Meta-Analysis (n=6,734)
Does genotype-guided P2Y12 inhibitor selection reduce bleeding and MACE in patients with ACS undergoing PCI?
In ACS patients undergoing PCI, genotype-guided de-escalation of P2Y12 inhibitors reduces bleeding and net adverse clinical events without increasing ischemic risk, particularly in the first 3 months.
BACKGROUND Genotype-guided P2Y12 inhibitor selection may improve outcomes in acute coronary syndrome (ACS) or percutaneous coronary interventions (PCI) patients. OBJECTIVES This study sought to assess the impact of guided therapy escalation or de-escalation vs conventional therapy. METHODS Randomized controlled trials comparing guided therapy using CYP2C19 genetic testing vs conventional therapy among patients with ACS undergoing PCI were searched and individual participant-level data obtained. The primary safety endpoint was time-to-first type 2, 3, or 5 Bleeding Academic Research Consortium (BARC) bleeding at 12 months. The primary efficacy endpoint was time-to-first major adverse cardiovascular event (MACE) at 12 months. RESULTS A total of 6,734 participants from 2 randomized controlled trials were available for analysis. After 1 year, there were no differences in the primary safety or efficacy endpoints with overall guided therapy vs conventional therapy. However, guided therapy reduced myocardial infarction (0.68; 95% CI: 0.48-0.97) and net adverse cardiovascular events (NACE) (0.85; 95% CI: 0.73-1.00) compared with conventional therapy. Guided therapy de-escalation reduced the primary safety endpoint (0.77; 95% CI: 0.62-0.97) and NACE (0.77; 95% CI: 0.62-0.94) with no significant difference in MACE, compared with conventional therapy. The primary safety and efficacy endpoints were similar between patients undergoing guided therapy escalation and conventional therapy groups. Time-dependent covariate analyses showed that overall guided therapy and de-escalation strategies reduced bleeding and NACE before 90 days, compared with conventional therapy. CONCLUSIONS These findings support evaluating genotype-guided therapy by separately analyzing de-escalation and escalation. In ACS patients undergoing PCI, genotype-guided de-escalation reduces bleeding and NACE without increasing MACE, with the greatest benefit in the first 3 months post-PCI. (Genotype-Guided versus Conventional Oral P2Y12 Inhibitors in Acute Coronary Syndrome: An Individual Patient Data Meta-analysis of Randomized Controlled Trials; PROSPERO CRD42024580431).
Galli et al. (Sun,) conducted a meta-analysis in Acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) (n=6,734). Genotype-guided P2Y12 inhibitor selection using CYP2C19 genetic testing vs. Conventional therapy was evaluated on Time-to-first type 2, 3, or 5 Bleeding Academic Research Consortium (BARC) bleeding and time-to-first major adverse cardiovascular event (MACE) at 12 months. Genotype-guided P2Y12 inhibitor de-escalation reduced BARC 2, 3, or 5 bleeding (HR 0.77; 95% CI 0.62-0.97) and NACE without increasing MACE compared with conventional therapy.