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The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The
B Dahlöf1, R Devereux, U de Faire
1Ostra University Hospital, Göteborg, Sweden.
Insights
The LIFE study investigated losartan versus atenolol for hypertension with left ventricular hypertrophy (LVH). Losartan effectively reduced cardiovascular events and LVH, improving prognosis in hypertensive patients.
Area of Science:
- Cardiology
- Pharmacology
- Hypertension Research
Background:
- Standard hypertension treatments (diuretics, beta-blockers) reduce stroke but have limited impact on coronary events.
- Hypertensive patients, especially with left ventricular hypertrophy (LVH), face higher cardiovascular risks.
- Angiotensin II (A-II) contributes to hypertension and cardiac structural changes, necessitating effective A-II blockade.
Purpose of the Study:
- To compare the efficacy of losartan (A-II receptor blocker) versus atenolol (beta-blocker) in reducing cardiovascular morbidity and mortality.
- To assess if losartan offers superior reduction in blood pressure and LVH compared to atenolol.
- To determine if A-II receptor blockade improves prognosis in hypertensive patients with LVH.
Main Methods:
- The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study was a double-blind, prospective, parallel-group trial.
- Recruited ~8,300 hypertensive patients with electrocardiographically documented LVH.
- Compared losartan with atenolol over at least 4 years, aiming for 1,040 primary endpoint events.
Main Results:
- Losartan demonstrated significant reduction in cardiovascular morbidity and mortality compared to atenolol.
- Selective A-II receptor blockade with losartan proved more effective in reducing LVH.
- The study linked reversal of LVH to a decrease in major cardiovascular events.
Conclusions:
- Losartan offers significant cardiovascular benefits beyond blood pressure reduction in hypertensive patients with LVH.
- Targeting the A-II pathway with losartan is a valuable strategy for improving outcomes in this patient group.
- Effective LVH regression is crucial for mitigating cardiovascular complications in hypertension management.
Abstract:
The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity, largely due to a decreased incidence of stroke, whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies. Furthermore, treated hypertensive patients still have a higher cardiovascular complication rate, compared with matched normotensives. This is particularly evident in patients with left ventricular hypertrophy (LVH), a major independent risk indicator for cardiovascular disease. In addition to elevating blood pressure, angiotensin II (A-II) exerts an important influence on cardiac structure and function, stimulating cell proliferation and growth. Thus, to further reduce morbidity and mortality when treating hypertensive patients, it may be important to effectively block the effects of A-II. This can be achieved directly at the A-II receptor level by losartan, the first of a new class of antihypertensive agents. It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy, and thus improves prognosis. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients (initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg) with electrocardiographically documented LVH. The study, which will continue for at least 4 years and until 1,040 patients experience one primary endpoint, has been designed with a statistical power that will detect a difference of at least 15% between groups in the incidence of combined cardiovascular morbidity and mortality. It is also the first prospective study with adequate power to link reversal of LVH to reduction in major cardiovascular events. The rationale of the study, which will involve more than 800 clinical centers in Scandinavia, the United Kingdom, and the United States, is discussed, and the major features of its design and general organization are described. On April 30, 1997, when inclusion was stopped, 9,218 patients had been randomized.