The ATLAS trial: ACE inhibitor dosing in chronic heart failure [Classics Series]

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1. When compared to a lower dose, high-dose angiotensin-converting-enzyme inhibitor significantly reduced the risk of hospitalization or death in patients with chronic heart failure

Original Date of Publication: December 7, 1999

Study Rundown: Physicians typically prescribe angiotensin-converting-enzyme (ACE) inhibitors to patients with chronic heart failure in lower doses than have been proven effective by large-scale studies. Nonetheless, research on the comparative benefits of high doses and low doses of ACE inhibitors was severely lacking. The ATLAS trial randomized 3,164 patients to receive low- or high-dose of the ACE inhibitor lisinopril for 29-58 months. This study demonstrated that compared with those in the low-dose group, patients in the high-dose treatment group had a significantly lower risk of death or hospitalization for any reason and additionally, significantly fewer hospitalizations for heart failure. These findings suggest that patients with heart failure due to left ventricular systolic dysfunction should not be maintained on low doses of ACE inhibitor unless they are intolerant of higher doses. Rather, tolerant patients should be placed on a higher dose treatment of ACE inhibitor due to its increased effectiveness as compared to low-dose treatment.

Click to read the study in Circulation

In-Depth [randomized, controlled study]: The ATLAS study, originally published in Circulation in 1999, sought to compare the effect of lisinopril dosage on mortality and morbidity of chronic heart failure patients. The study randomly assigned 3,164 patients with New York Heart Association (NYHA) class II to IV heart failure and an ejection fraction of ≤30% to treatment with either a high-dose (32.5-35 mg daily) or low-dose (2.5-5.0 mg daily) of lisinopril, an ACE inhibitor. The trial was conducted in 287 hospitals across 19 countries. The duration of follow-up ranged from 39 to 58 months.

The trial found that patients randomized to receive high-dose lisinopril experienced a 12% lower risk of hospitalization or death for any reason (P=0.002) and 24% fewer hospitalizations for heart failure (P=0.002) as compared to patients in the low-dose group. Patients in the high-dose group did experience dizziness and renal insufficiency more frequently. However, these side effects did not lead to lower compliance with medication in the high-dose group. Based on the findings of this study, it is suggested that patients with chronic heart failure be treated with the highest tolerable doses of ACE inhibitor.

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