Effects of the concomitant administration of xanthine oxidase inhibitors with zofenopril or other ACE-inhibitors in post-myocardial infarction patients: a meta-analysis of individual data of four randomized, double-blind, prospective studies

• Published in: BMC cardiovascular disorders 2018-06, Vol.18 (1), p.112-112, Article 112
• Main Authors: Borghi, Claudio, Omboni, Stefano, Reggiardo, Giorgio, Bacchelli, Stefano, Esposti, Daniela Degli, Ambrosioni, Ettore
• Format: Article
• Language: English
• Subjects: Acute myocardial infarction; Aged; Analysis; Angiotensin-converting enzyme inhibitors; Angiotensin-Converting Enzyme Inhibitors - adverse effects; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Antioxidants; Captopril - adverse effects; Captopril - analogs & derivatives; Captopril - therapeutic use; Cardiac output; Cardiovascular disease; Cardiovascular diseases; Coronary vessels; Data processing; Diagnosis; Double-Blind Method; Double-blind studies; Endothelium; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - therapeutic use; Enzymes; Female; Health aspects; Heart attacks; Heart failure; Humans; Hypertension; Hyperuricemia; Ischemia; Lisinopril - therapeutic use; Male; Meta-analysis; Middle Aged; Mortality; Myocardial infarction; Myocardial Infarction - diagnosis; Myocardial Infarction - drug therapy; Myocardial Infarction - mortality; Myocardial Infarction - physiopathology; Oxidative stress; Patients; Progression-Free Survival; Prospective Studies; Ramipril - therapeutic use; Randomized Controlled Trials as Topic; Retrospective Studies; Rheumatism; Risk Factors; Studies; Survival; Systematic review; Time Factors; Treatment Outcome; Uric acid; Xanthine; Xanthine oxidase; Xanthine Oxidase - antagonists & inhibitors; Xanthine oxidase inhibitors
• ISSN: 1471-2261; 1471-2261
• DOI: 10.1186/s12872-018-0800-x

Oxidative stress is increased in hyperuricemic patients with acute myocardial infarction (AMI). Use of sulfhydryl ACE-inhibitors (ACEIs), such as zofenopril or captopril, plus xanthine oxidase inhibitors (XOIs), may potentially result in enhanced antioxidant effects and improved survival. We verified the benefit of such combination in a randomly stratified sample of 525 of the 3630 post-AMI patients of the four randomized prospective SMILE (Survival of Myocardial Infarction Long-term Evaluation) studies. One hundred sixty-five (31.4%) patients were treated with XOIs (79 under zofenopril, 86 placebo, lisinopril or ramipril), whereas 360 were not (192 zofenopril, 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). 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 under treatment with zofenopril + 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 + XOIs [1.82 (0.78-4.26), p = 0.169]. Our retrospective analysis suggests an improved survival free from MACE in post-AMI patients treated with a combination of an urate lowering drug with antioxidant activity and an ACEI, with best effects observed with zofenopril.