title: The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group.
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.
authors.affiliation: Ostra University Hospital, Göteborg, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Dahlöf
authors.forename: R
authors.initials: R
authors.lastname: Devereux
authors.forename: U
authors.initials: U
authors.lastname: de Faire
authors.forename: F
authors.initials: F
authors.lastname: Fyhrquist
authors.forename: T
authors.initials: T
authors.lastname: Hedner
authors.forename: H
authors.initials: H
authors.lastname: Ibsen
authors.forename: S
authors.initials: S
authors.lastname: Julius
authors.forename: S
authors.initials: S
authors.lastname: Kjeldsen
authors.forename: K
authors.initials: K
authors.lastname: Kristianson
authors.forename: O
authors.initials: O
authors.lastname: Lederballe-Pedersen
authors.forename: L H
authors.initials: LH
authors.lastname: Lindholm
authors.forename: M S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: P
authors.initials: P
authors.lastname: Omvik
authors.forename: S
authors.initials: S
authors.lastname: Oparil
authors.forename: H
authors.initials: H
authors.lastname: Wedel
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D000804:Angiotensin II / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001262:Atenolol / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use*; D019808:Losartan; D008297:Male; D008875:Middle Aged; D012107:Research Design; D013777:Tetrazoles / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D001262:Atenolol; D019808:Losartan