Losartan Intervention For Endpoint reduction in hypertension (LIFE) study - LIFE

Description:

This was a double-masked, randomized, parallel-group trial comparing use of losartan with atenolol in patients with hypertension and left ventricular hypertrophy (LVH).

Hypothesis:

Selective angiotensin-II type 1-receptor antagonism with losartan would be more effective than beta-blockade with atenolol in reducing cardiovascular morbidity and death in patients with essential hypertension and signs of LVH.

Study Design

  • Placebo Controlled
  • Randomized
  • Blinded
  • Parallel

Patients Screened: 10,780
Patients Enrolled: 9,193
Mean Follow Up: ≤4 years (mean 4.8 years)
Mean Patient Age: 55-80 years
Female: 54

Patient Populations:

Aged 55-80 years, previously treated or untreated hypertension, systolic BP 160-200 mm Hg, diastolic BP 95-115 mm Hg, and ECG signs of LVH

Exclusions:

Secondary hypertension; MI or stroke within the previous six months; angina pectoris requiring treatment with beta-blockers or calcium-antagonists; heart failure or LV ejection fraction of ≤40%; or disorder that, in the treating physician's opinion, required treatment with losartan or another angiotensin-II type 1-receptor antagonist, atenolol, or another beta-blocker, hydrochlorothiazide, or angiotensin-converting enzyme inhibitors

Primary Endpoints:

Composite of death, MI, or stroke

Secondary Endpoints:

Changes in systolic and diastolic BP, individual endpoints in composite (death, MI, or stroke), angina pectoris or heart failure requiring admission to hospital, coronary or peripheral revascularization procedures, resuscitated cardiac arrest, and new-onset diabetes

Drug/Procedures Used:

Randomization to losartan-based or atenolol-based regimens after 1-2 weeks of placebo, and drugs dosed to reach a target blood pressure (BP) of <140/90 mm Hg per titration schedule

Principal Findings:

BP fell by 30.2/16.6 in the losartan arm and 29.1/16.8 mm Hg in the atenolol arm (treatment difference, p=0.017 for systolic BP and p=0.37 for diastolic BP). The primary composite endpoint occurred in 11% of losartan-treated patients and 13% of atenolol-treated patients (hazard ratio [HR] 0.87, p=0.021).

Cardiovascular mortality was 4% in the losartan arm and 5% in the atenolol arm (HR 0.89, p=0.206). Stroke was lower in the losartan group (5% vs. 7%, HR 0.75, p=0.001). New-onset diabetes occurred less frequently in the losartan arm (6% vs. 8%, HR 0.75, p=0.001).

Interpretation:

Unlike the CAPPP, NORDIL, and STOP-HTN2 trials, which compared angiotensin-converting enzyme inhibitors or calcium channel blockers with beta-blockers and diuretics for treatment of hypertension and saw no difference in efficacy, the LIFE trial showed a significant treatment effect with use of the angiotensin II type 1-receptor antagonist losartan. Losartan was associated with a greater reduction in the composite endpoint of death, myocardial infarction (MI), and stroke (with most of the significance driven by the difference in stroke), than the beta-blocker atenolol for a similar reduction in BP. Additional benefits included a 25% reduction in new-onset diabetes, possibly due to an effect on insulin resistance.

This trial was designed to examine the efficacy of losartan in high-risk hypertensive patients with signs of LVH; generalizability of the results to lower risk hypertensive patients cannot be made. In addition, no inferences can be made regarding how losartan would compare to a diuretic in efficacy.

References:

Dahlof B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995-1003.

Presented at the European Society of Cardiology, Vienna, Austria, September 2003.

Clinical Topics: Prevention, Hypertension

Keywords: Hypertrophy, Left Ventricular, Losartan, Stroke, Myocardial Infarction, Diuretics, Electrocardiography, Insulin Resistance, Calcium Channel Blockers, Hypertension, Diabetes Mellitus


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