Background Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). In these patients, use of sulfhydrylACE-inhibitors (ACEIs), such as zofenopril or captopril, and xanthine oxidase inhibitors (XOIs), may potentially result in an enhanced antioxidant effect and improved survival. However, the benefit of such combination in post-myocardial infarction has never been verified.
Objectives To test the usefulness of the combination therapy Zofenopril + XOI in improving survival free from MACE in post-AMI patients
Methods We re-analyzed the data of the four SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies by grouping patients according to the type of ACEIs and the use of XOIs. 165 (31.4%) of the 525 patients were treated with XOIs (79 under zofenopril and 86 under placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril and 168 placebo or other ACEIs). In these four groups, we separately estimated the 1-year combined risk of major cardiovascular events (MACE, death or hospitalization for cardiovascular causes).
Results MACE occurred in 10.1% of patients receiving zofenopril + XOIs, in 18.6% receiving placebo or other ACEIs + XOIs, in 13.5% receiving zofenopril without XOIs and in 22.0% receiving placebo or other ACEIs, but no XOIs (p=0.034 across groups). Rate of survival free from MACE was significantly larger in patients treated with zofenopril and XOIs than with other ACEIs with no XOIs [hazard ratio: 2.29 (1.06, 4.91), p=0.034]. A non-significant trend for superiority of zofenopril + XOIs combination was observed vs. zofenopril alone [1.19 (0.54, 2.64), p=0.669] or vs. placebo or other ACEIs combined with XOIs [1.82 (0.78, 4.26), p=0.169].
Conclusions Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an ACEI and urate lowering drug with antioxidant activity.
Disclosure of Interest None declared