Background: Genotype-guided P2Y12 inhibitor selection may improve outcomes in acute coronary syndrome (ACS) or percutaneous coronary interventions (PCI) patients.
Objectives: To assess the impact of guided therapy (GT) escalation or de-escalation vs. conventional therapy (CT).
Methods: Randomized controlled trials (RCTs) comparing GT using CYP2C19 genetic testing vs. CT 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 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 two RCTs were available for analysis. After 1 year, 12 there were no differences in the primary safety or efficacy endpoints with overall GT vs. CT. However, GT 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 CT. GT 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 to CT. The primary safety and efficacy endpoints were similar between patients undergoing GT escalation and CT groups. Time-dependent covariate analyses showed that overall GT and de-escalation strategies reduced bleeding and NACE prior to 90 days, compared to CT.
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.
Editors
Editor-in-Chief
Harlan M. Krumholz, MD, SM, FACC
CME Editor
Ragavendra R. Baliga, MD
Author
Mattia Galli, MD
Important Dates
Date of Release: February 9, 2026
Term of Approval/Date of CME/MOC Expiration: February 8, 2027