Effects of canrenoate plus angiotensin-converting enzyme inhibitors versus angiotensin-converting enzyme inhibitors alone on systolic and diastolic function in patients with acute anterior myocardial infarction

Abstract

Background Aldosterone (ALDO) exerts profibrotic effects, acting via the mineralocorticoid receptors in cardiovascular tissues. Aldosterone antagonism in combination with angiotensin-converting enzyme inhibition may better protect against the untoward effects of ALDO than angiotensin-converting enzyme inhibition alone. Methods In a double-blind randomized study, the tolerability and efficacy of canrenoate (25 mg/d) plus captopril versus captopril alone were evaluated in 510 patients with an acute anterior myocardial infarction (MI), a serum creatinine concentration <2.0 mg/dL, and a serum potassium level <5.0 mmol/L. Three hundred forty-one patients received captopril and 25-mg canrenoate (group A). Group B (346 patients) received captopril and placebo. At baseline and at 10, 90, and 180 days after admission, Doppler echocardiography was performed. Results Clinical and demographic aspects were similar in both groups. In addition, baseline cardiac enzyme levels, left ventricular function, and incidence of surgical interventions and angioplasty were comparable. Overall, creatinine, blood urea, and serum potassium levels did not show significant differences between groups. However, in 18 patients in group A, increases in serum potassium levels to >5.5 mEq/L and creatinine levels to >2.0 mg/L after 10 days of treatment were observed. At 180 days, the mitral E-wave–A-wave ratio was higher (P = .0001) and left ventricular end-systolic volume was smaller (P = .0001) in patients treated with canrenoate than in those receiving placebo. No further side effects were observed during the study period. Conclusions Our data suggest that the combination of captopril plus canrenoate is well tolerated after an acute MI and has beneficial effect on systolic and diastolic parameters and may decrease post-MI remodeling.