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,...
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BACKGROUND 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 OBJECTIVE 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 METHODS 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 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 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 CONCLUSIONS 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