Benefits of losartan on cardiovascular morbidity and mortality in patients with isolated systolic hypertension: a LIFE substudy - LIFE Elderly Substudy

Description:

Comparison of losartan to atenolol in elderly patients with isolated systolic hypertension and left ventricular hypertrophy.

Hypothesis:

Losartan administration to elderly patients with left ventricular hypertrophy will lead to improved outcomes compared to atenolol.

Study Design

Study Design:

Patients Screened: 10,778
Patients Enrolled: 9,222 (1326 in this substudy)
Mean Patient Age: 55-80 years Mean 70 years
Female: 60%

Patient Populations:

1) Age 55-80 years 2) Previously treated or untreated hypertension 3) Systolic blood pressure 160-200 mm Hg and diastolic blood pressure <90 mm Hg 4) ECG criteria of LVH using Cornell Voltage Product criteria or Sokolow-Lyon Voltage

Exclusions:

1) Secondary hypertension 2) Stroke or myocardial infarction within previous 6 months 3) Angina requiring treatment with beta-blocker or calcium channel blocker 4) Heart failure or LVEF <40% 5) Condition requiring treatment with angiotensin II receptor antagonist, atenolol, or ACE inhibitor

Secondary Endpoints:

1) All cause mortality 2) Stroke 3) Fatal/nonfatal myocardial infarction 4) Cardiovascular death 5) New onset diabetes 6) Treatment discontinuation

Drug/Procedures Used:

Losartan 50 mg/day compared to atenolol 50 mg/day titrated upward to SBP <140 mm Hg

Concomitant Medications:

HCTZ added after 2 months if SBP >140 mm Hg, other agents added if losartan or atenolol dose 100 mg/day, HCTZ dose 25 mg/day and SBP >140 mm Hg

Principal Findings:

When analyzed by both ECG criteria, there was a significant difference in LVH regression favoring losartan (p<0.001). There was also a decreased incidence of new onset diabetes in the losartan treated group (RR 36%, p=0.038). Cardiovascular mortality (RR 46%, p=0.011) and total mortality (RR 28%, p=0.048) were also significantly lower in the losartan treated group. A lower risk of stroke was noted with a RR of 41%, p=0.02. Both the occurrence of the primary composite endpoint (RR 26%, p=0.051) and of fatal/nonfatal myocardial infarction (RR13%, p=0.056) did not achieve statistical significance. Losartan was significantly better tolerated with a lower incidence of treatment discontinuation (25% losartan vs. 32% atenolol; p=0.02).

Interpretation:

This trial showed a beneficial effect with regard to regression of LVH and fewer cardiovascular events, strokes and onset of diabetes in the subgroup of elderly patients with systolic hypertension enrolled in the LIFE trial. No data were presented regarding absolute reductions in blood pressure in each group, and based on these data, it is unknown whether the benefit of losartan is independent of the blood pressure lowering effect. In so far as losartan may be better tolerated than atenolol, and because losartan in this subgroup may be more beneficial, losartan can be considered as an alternative to atenolol for systolic hypertension in the elderly. The known synergistic effect of HCTZ with angiotensin II receptor antagonists in reducing blood pressure may have led to additional benefit and such an effect has not been demonstrated with atenolol. While the composite endpoint difference did not reach statistical significance, such a difference favoring losartan may have been detected if a greater number of events were larger. Based on these findings, it is unclear if these benefits can be generalized to patients with systolic and diastolic hypertension, younger age or no LVH. While these substudy data are provocative, further prospective data validating these findings is lacking at present.

References:

Presented by S.E. Kjeldsen at the Annual Meeting of the European Society of Cardiology, September 2, 2002.

Clinical Topics: Prevention, Statins, Hypertension

Keywords: Hypertrophy, Left Ventricular, Angiotensin Receptor Antagonists, Losartan, Myocardial Infarction, Stroke, Hydrochlorothiazide, Electrocardiography, Hypertension, Diabetes Mellitus


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