[Clinical study of the month. The ATLAS study].
The Atlas Study was set up to compare the efficacy and safety of low doses and high doses of ACE inhibition by lisinopril on the risk of death and hospitalization in chronic heart failure. Three thousand one hundred sixty-four patients with class II to IV heart failure and an ejection fraction below 30% were randomly assigned to double blind treatment with either low doses (2.5-5 mg/daily, n = 1596) or high doses (32.5-35 mg/daily, n = 1568) of the ACE inhibitor lisinopril for 39 to 58 months while background therapy for heart failure was continued. Patients in the high dose group had a non significant 8% lower risk of death (p = 0.128), but a significant 12% lower risk of death or hospitalizations for any reason (p = 0.002) and 24% fewer hospitalizations for heart failure (p = 0.002). Side-effects such as dizziness and renal insufficiency were more frequently encountered in the high dose group, but there was no difference between the two groups in terms of number of patients requiring discontinuation of study medication. These findings indicate that patients with heart failure should not, as too frequently is, be maintained on very low dose of an ACE inhibitor unless this is the only dose that can be tolerated. The patients are expected to benefit more if they receive higher doses close to those used in the large clinical trials which have demonstrated a reduction by ACE inhibition in morbidity and mortality in heart failure.
Kulbertus
H
H
Université de Liège, Service de Cardiologie.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006760:Hospitalization; D006801:Humans; D017706:Lisinopril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018570:Risk Assessment; D016896:Treatment Outcome
D000806:Angiotensin-Converting Enzyme Inhibitors; D017706:Lisinopril