Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery

Abstract

Objective: This study tested the hypothesis that interruption of the renin-angiotensin system with either an angiotensin-converting enzyme inhibitor or a mineralocorticoid receptor antagonist will decrease the prevalence of atrial fibrillation after cardiac surgery.

Design: Randomized double-blind placebo-controlled study.

Setting: University-affiliated hospitals.

Patients: Four hundred forty-five adult patients in normal sinus rhythm undergoing elective cardiac surgery.

Interventions: One week to 4 days prior to surgery, patients were randomized to treatment with placebo, ramipril (2.5 mg the first 3 days followed by 5 mg/day, with the dose reduced to 2.5 mg/day on the first postoperative day only), or spironolactone (25 mg/day).

Measurements: The primary endpoint was the occurrence of electrocardiographically confirmed postoperative atrial fibrillation. Secondary endpoints included acute renal failure, hyperkalemia, the prevalence of hypotension, length of hospital stay, stroke, and death.

Main results: The prevalence of atrial fibrillation was 27.2% in the placebo group, 27.8% in the ramipril group, and 25.9% in the spironolactone group (p=.95). Patients in the ramipril (0.7%) or spironolactone (0.7%) group were less likely to develop acute renal failure than those randomized to placebo (5.4%, p=.006). Patients in the placebo group tended to be hospitalized longer than those in the ramipril or spironolactone group (6.8±8.2 days vs. 5.7±3.2 days and 5.8±3.4 days, respectively, p=.08 for the comparison of placebo vs. the active treatment groups using log-rank test). Compared with patients in the placebo group, patients in the spironolactone group were extubated sooner after surgery (576.4±761.5 mins vs. 1091.3±3067.3 mins, p=.04).

Conclusions: Neither angiotensin-converting enzyme inhibition nor mineralocorticoid receptor blockade decreased the primary outcome of postoperative atrial fibrillation. Treatment with an angiotensin-converting enzyme inhibitor or mineralocorticoid receptor antagonist was associated with decreased acute renal failure. Spironolactone use was also associated with a shorter duration of mechanical ventilation after surgery.

Trial registration: ClinicalTrials.gov NCT00141778.

Figure 1

Enrollment and study progress.

Figure 2

(A) Mean arterial pressure (MAP) during surgery and on each postoperative day (POD). (B) Proportion of patients treated with specific vasopressors and inotropes during surgery. Data are presented as means±SEM.

Figure 3

(A) Angiotensin-converting enzyme (ACE) and (B) aldosterone concentrations at the initiation of surgery in patients randomized to placebo, ramipril or spironolactone. (C) Serum potassium concentrations during surgery and on each postoperative day (POD). Data are presented as means±SEM. *P<0.05 versus the other two study groups, †P<0.05 versus spironolactone group.

Figure 4

Change in creatinine after controlling for baseline glomerular filtration rate and diuretic use on the day of surgery through the third postoperative day. Data are presented as estimated marginal mean±SEM. The estimated marginal means were calculated after controlling for baseline glomerular filtration rate and diuretic use. P<0.01 for placebo versus either ramipril or spironolactone.