ACE inhibitor dosage at the time of listing predicts survival

Background: To be listed for heart transplantation (HTx), optimization of the dosage of angiotensin converting enzyme (ACE) -inhibitors is recommended worldwide even though this issue has not been thoroughly investigated in the pre-transplantation cohort. Objective: The aim of this database study was to analyze the prognostic impact of a pre-defined high vs a low ACE inhibitor dose range at the time of listing for elective HTx in addition to various previously established prognostic factors. Methods: Medical records from 237 patients (84% male, mean age 54 years) admitted between January 1995 and January 1998 from 25 different centers in Austria were reviewed. Forty-seven percent were taking greater than or equal to 75 mg captopril, 220 mg enalapril, greater than or equal to 20 mg lisinopril or greater than or equal to 5 mg ramipril daily ("high-dose" group) and 53% received smaller doses ("low-dose" group). Results: No significant differences between groups were detected at baseline except that patients with higher ACE inhibitor doses were more likely to take nitrates, beta-blockers and amiodarone, received higher furosemide doses and had higher serum gamma-glutamyl transferase levels. Follow-up was 328 days (248 SD) with 16% deaths in the "high-dose" group vs 288 days (270 SD) with 25% deaths in the "low-dose" group. Kaplan-Meier survival curves demonstrated a significant difference over time between the two treatment groups (P = 0.03). Furthermore, dichotomized ACE inhibitor treatment at the time of listing was the strongest independent single predictor of mortality (P = 0.01) with only blood pressure (P = 0.02), alanine transaminase (P = 0.02) and left ventricular end diastolic diameter (P = 0.02) providing additional prognostic information. To explain these findings several factors have to be considered a) greater benefit with higher ACE inhibitor doses b) sicker patients receiving lower ACE inhibitor doses and c) more experienced heart failure care of the "high-dose" group. Conclusions: Heart transplantation candidates who, for whatever reason, receive ACE-inhibitors below the recommended dosages, are at increased mortality risk and thus merit greater scrutiny.