Abstract 14540: Genetic Variations Optimized Treatment Benefit of the Angiotensin-Converting- Enzyme Inhibitors in Patients With Stable Coronary Artery Disease: A 12-Year Follow-Up Study
BACKGROUND: The objective of this study was to evaluate the effects of angiotensin converting enzyme (ACE) inhibitors and pharmacogenetic interaction in patients with coronary artery disease (CAD).
METHODS: Subjects with angiographic CAD were recruited from 1995 to 2003. Baseline characteristics and genetic polymorphisms (ACE gene insertion/deletion [I/D] polymorphism, six polymorphisms of the angiotensinogen [AGT] gene, and A1166C polymorphisms of the angiotensin II type I receptor gene [AGT1R]) were collected. Patients were randomized to 2 groups (ACE inhibitor or No-ACE inhibitor) and followed for up to 12 years. Kaplan-Meier curves and Cox regression models were used to demonstrate the survival and major cardiovascular events (MACE) event-free survival trend. Pharmacogenetic effects were determined by several Cox regression models.
RESULTS: Of the 784 patients, 432 were treated with ACE inhibitors and 352 were not. Prescription of ACE inhibitors was associated with a lower rate of MACE at 4000 days. In addition, ACE I/D gene D and AGT1R gene C allele were associated with a higher rate of MACE in a multivariate regression analysis (HR: 1.49, 95% CI: 1.26∼1,75, P = 0.008; HR: 1.42, 95% CI: 1.04∼1,94, P = 0.027, respectively). This effect could be attenuated by the pharmacogenetic interaction of ACE inhibitors and the ACE gene (ACE inhibitors*ACE gene, HR: 0.8, 95% CI: 0.62∼0.94, P = 0.03).
CONCLUSIONS: The use of ACE inhibitors was associated with a significant decrease in MACE in patients diagnosed with CAD. Genetic variants were also associated with event-free survival, but their effects were modified by the use of ACE inhibitors.
- © 2011 by American Heart Association, Inc.