ACEI Dosage Optimization in Heart Failure

Abstract & Commentary

Synopsis: Optimization of angiotensin-coverting enzyme inhibitors in a heart failure program can markedly reduce readmissions and lower the cost of care in heart failure patients.

Source: Luzier AB, et al. Am J Cardiol 2000;86: 519-523.

Since the atlas trial was published, there has been increased interest in the effects of optimizing angiotensin converting enzyme inhibitors (ACEIs) in heart failure patients. Thus, Luzier and colleagues conducted a prospective intervention study in 110 patients with systolic left ventricular dysfunction entered into a multidisciplininary heart failure disease management program. They were divided into three groups. Group A consisted of 28 patients on at least recommended doses of ACEI (captopril 150 mg, enalapril 20 mg, lisinopril 20 mg, or quinapril 40 mg daily), which averaged 30 mg of enalapril or its equivalent daily. Some patients were up-titrated so the final average dose of enalapril was 36 mg daily. The 82 patients (75%) considered to be on suboptimal ACEI or none were divided into group B, which consisted of 51 patients in whom the recommendation to increase ACEI was accepted by the treating physician, and those in whom it was not were in group C. In group B, ACEI was initiated in 26 (51%) patients and was increased in the rest to a mean of 16 mg daily for the group. Mean ACEI dose in Group C was 6 mg/d. Readmission rates at 90 days follow-up were: group A = 14%, B = 19%, and C = 29% (P = 0.02), and at 180 days were A = 31%, B = 35%, and C = 63% (P < 0.007). The higher readmission rate in group C was associated with higher direct costs. Luzier et al concluded that optimization of ACEI in a heart failure program can markedly reduce readmissions and lower the cost of care in heart failure patients.

Comment by Michael H. Crawford, MD

Several studies have documented suboptimal ACEI usage in heart failure patients and optimization of ACEI is believed to be an important aspect of multidisciplinary heart failure management programs. The bar for ACEI dosages was raised by the ATLAS trial,1 which showed that doses of lisinopril greater than 30 mg/d resulted in better outcome than less than 5 mg/d. However, the lisinopril dose in other successful trials was 20 mg/d and this is the recommendation of the AHCPR guidelines. Unfortunately, ATLAS did not test this dose. An analysis of this discrepancy by Drs. Nicklas, Cohn, and Pitt2 recommend that physicians continue to use ACEI dosages from randomized clinical trials (i.e., lisinopril 20/d) rather than the high doses used in ATLAS. The rationale for this recommendation was that the difference in benefits between high-and low-dose ACEI in ATLAS was small and it is likely that the intermediate doses used in randomized clinical trials would have the same effect as higher doses.

With regard to the end point of rehospitalization, this ACEI dose optimization study supports the recommendation for intermediate doses since there was no difference in outcome between groups A (36 mg/d enalapril) and B (16 mg/d), but group C (6 mg/d) did worse. One caveat to this study is that half of the group B patients were not on ACEI at initiation into the study, but 96% were after the intervention. So this is not just a study of dose optimization, because it includes initiating ACEI for half the patients. This clouds the results with regard to dose optimization.

The reason given for why patients were either not on ACEI or at low doses in group B was fear of adverse effects: 14 were intolerant to ACEI; of these, 11 with cough were put on losartan and three with renal insufficiency were put on hydralazine/nitrates. These patients were included in group B and contribute to the outcome results. Thus, ACEI optimization in this study also included recognized alternative therapy.


1. Packer M, et al. ATLAS trial. Circulation 1999;100:2312-2318.

2. Nicklas JM, et al. J Cardiac Failure 2000;6:165-168.