High- versus low-dose angiotensin converting enzyme inhibitor therapy in the treatment of heart failure: an economic analysis of the Assessment of Treatment with Lisinopril and Survival (ATLAS) trial.

BACKGROUND Angiotensin-converting enzyme (ACE) inhibitors reduce heart failure death and hospitalization. Prescribed doses often are lower than randomized clinical trial (RCT) targets and practice guideline recommendations. OBJECTIVE To assess the cost-effectiveness of high- versus low-dose ACE inhibitor therapy in the ATLAS trial. STUDY DESIGN A 19-nation RCT of high-dose (32.5-35.0 mg/day) versus low-dose (2.5-5.0 mg/day) lisinopril in 3164 patients with class II-IV heart failure and left ventricular ejection fraction < or = 30%. METHODS Data on clinical outcomes and major cost events (hospitalizations and drug utilization) were collected prospectively. Hospital costs were estimated using Medicare and representative managed care diagnosis-related group reimbursement rates. ACE inhibitor drug costs were estimated using US average wholesale prices. Costs were discounted at 3% annually. RESULTS Patients in the high-dose lisinopril group had fewer hospitalizations (1.98 vs 2.22, P = .014) and hospital days (18.28 vs 22.22, P = .002), especially heart failure hospitalizations (0.64 vs 0.80, P = .006) and heart failure hospital days (6.02 vs 7.45, P = .028) compared with the low-dose group. The high-dose lisinopril group also had lower heart failure hospital costs (dollars 5114 vs dollars 6361, P = .006) but higher ACE inhibitor drug costs (dollars 1368 vs dollars 855, P = .0001). Total hospital and drug costs were similar between high- and low-dose lisinopril groups (mean difference dollars -875, 95% CI dollars -2613 to dollars 884). Sensitivity analyses confirmed these findings. CONCLUSIONS Cost savings from fewer heart failure hospitalizations offset higher ACE inhibitor costs in the high-dose group. The improved clinical outcomes were achieved without increased treatment costs.