THE LOSARTAN INTERVENTION FOR END-POINT REDUCTION (LIFE) IN HYPERTENSION STUDY - RATIONALE, DESIGN, AND METHODS

The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity, largely due to a decre ased incidence of stroke, whereas the beneficial effects of antihypert ensive therapy on the occurrence of coronary events have been less tha n expected from epidemiological studies. Furthermore, treated hyperten sive patients still have a higher cardiovascular complication rate, co mpared with matched normotensives. This is particularly evident in pat ients with left ventricular hypertrophy (LVH), a major independent ris k indicator for cardiovascular disease. In addition to elevating blood pressure, angiotensin II (A-II) exerts an important influence on card iac structure and function, stimulating-cell proliferation and growth. Thus, to further reduce morbidity and mortality when treating hyperte nsive patients, it may be important to effectively block the effects o f A-II. This can be achieved directly at the A-II receptor level by lo sartan, the first of a new class of antihypertensive agents. It theref ore seems pertinent to investigate whether selective A-II receptor blo ckade with losartan not only lowers blood pressure but also reduces LV H more effectively than current therapy, and thus improves prognosis. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertensio n study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker aten olol on the reduction of cardiovascular morbidity and mortality in app roximately 8,300 hypertensive patients (initial sitting diastolic bloo d 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 o f combined cardiovascular morbidity and mortality. It is also the firs t-prospective study with adequate power to link reversal of LVH to red uction in major cardiovascular events. The rationale of the study, whi ch will involve more than 800 clinical centers in Scandinavia, the Uni ted Kingdom, and the United States, is discussed, and the major featur es of its design and general organization are described. On April 30, 1997, when inclusion was stopped, 9,218 patients had been randomized. (C) 1997 American Journal of Hypertension, Ltd.