Efficacy of zofenopril in combination with thiazide diuretics in patients with acute myocardial infarction: a pooled individual data analysis of four randomized, double-blind, controlled, prospective ...

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Background In the Survival of Myocardial Infarction Long Term Evaluation SMILE studies early administration of zofenopril after acute myocardial infarction AMI was prognostically beneficial as compared to placebo and other angiotensin converting enzyme inhibitors ACEIs such as lisinopril and ramipril Here we investigated whether zofenopril efficacy could be affected by a concomitant use of thiazide diuretics TDs Methods This was a post hoc analysis of pooled individual patient data from the SMILE studies Patients treated with other diuretics than TDs were excluded The primary study endpoint was the 1 year combined occurrence of death or hospitalization for CV causes with or without TD Results Among 2 995 patients 263 8 8 were treated with a combination including a TD TD whereas 2 732 91 2 were not treated with any diuretic TD Proportions of subjects who were treated with TD were equally distributed p 0 774 within the placebo zofenopril and other ACEIs groups The 1 year risk of major cardiovascular events was similar in TD 18 3 and TD 16 8 patients hazard ratio HR 1 04 95 CI 0 74 1 45 p 0 838 After stratifying per concomitant treatment and TD the 1 year risk of CV events was significantly lower with zofenopril than with placebo HR 0 70 95 CI 0 55 0 88 p 0 002 and other ACEIs HR 0 58 95 CI 0 46 0 74 p 0 0001 Treatment with ACEIs and TD as concomitant therapy was associated with a larger blood pressure BP reduction p 0 0001 for systolic BP and p 0 045 for diastolic BP Conclusion In post AMI patients zofenopril maintained its positive impact on prognosis compared to placebo or other ACEIs regardless concomitant TD administration In this setting TD shows advantages in managing the most difficult hypertensive patients
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