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[Clinical study of the month. The ATLAS study]
1Université de Liège, Service de Cardiologie.
Insights
Higher doses of ACE inhibitors like lisinopril significantly reduce hospitalizations in chronic heart failure patients. This study suggests optimizing dosage for better outcomes in heart failure management.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Chronic heart failure (CHF) management often involves ACE inhibitors.
- Optimal dosing strategies for ACE inhibitors in CHF require further investigation.
Purpose of the Study:
- To compare the efficacy and safety of low-dose versus high-dose ACE inhibition with lisinopril in patients with chronic heart failure.
- To assess the impact of lisinopril dosage on mortality and hospitalization risks.
Main Methods:
- The Atlas Study randomized 3,164 patients with CHF (NYHA class II-IV, ejection fraction <30%) to receive either low-dose (2.5-5 mg/day) or high-dose (32.5-35 mg/day) lisinopril.
- Patients received double-blind treatment for 39-58 months, with continued background heart failure therapy.
Main Results:
- High-dose lisinopril showed a significant 12% reduction in death or hospitalization (p=0.002) and a 24% reduction in heart failure hospitalizations (p=0.002).
- A non-significant 8% lower risk of death was observed in the high-dose group (p=0.128).
- Increased dizziness and renal insufficiency were noted with high doses, but medication discontinuation rates were similar.
Conclusions:
- Patients with chronic heart failure may benefit from higher doses of ACE inhibitors, approaching those used in major clinical trials.
- Avoidance of very low ACE inhibitor doses is recommended unless necessitated by tolerability issues.
- Optimizing ACE inhibitor dosage can improve outcomes in heart failure management.
Abstract:
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.