Coronary disease & ACSSecondary analysis
Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial
- Secondary analysis of the ODYSSEY OUTCOMES randomised trial
- post hoc
- double-blind
- placebo-controlled
Authors' conclusion
A high PRS for CAD is associated with elevated risk for recurrent MACE after acute coronary syndrome and a larger absolute and relative risk reduction with alirocumab treatment, providing an independent tool for risk stratification and precision medicine.
Study context
- Population
- Patients with ACS and elevated atherogenic lipoproteins despite optimized statin treatment, with available DNA samplesof 18,924 in trial
- Participants
- 11,953 patients
- Comparison
- Alirocumab vs placebo, by genome-wide polygenic risk score for coronary artery disease (CAD)
- Primary endpoint
- MACE:
- Death of CAD
- Nonfatal MI
- Ischemic stroke
- Unstable angina requiring hospitalization
Primary result
As reported in the abstract
MACE reduction by alirocumab vs placebo, by PRS subgroup
Alirocumab vs PlaceboHazard ratio (95% CI)P value
high PRS (>90th percentile): absolute reduction 6.0%, RR reduction 37%
0.63(0.46–0.86)
P = 0.004low PRS (≤90th percentile): absolute reduction 1.5%, RR reduction 13%
0.87(0.78–0.98)
P = 0.022Further findings
MACE incidence in placebo, by PRS
P < 0.001
- Major adverse cardiovascular events (MACE) incidence in placebo, by polygenic risk scores (PRS): not explained by baseline LDL-C or other established risk factors
Original publication
Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial. Circulation. Published 11 November 2019. doi:10.1161/circulationaha.119.044434
Summarised from the published abstract; every number is checked against it