Blood pressure reduction and antihypertensive medication use in the losartan intervention for endpoint reduction in hypertension (LIFE) study in patients with hypertension and left ventricular hypertrophy

University of Helsinki, Helsinki, Uusimaa, Finland
Current Medical Research and Opinion (Impact Factor: 2.37). 03/2007; 23(2):259-70. DOI: 10.1185/030079906X162854
Source: PubMed

ABSTRACT To compare blood pressure response and antihypertensive medication use visit-by-visit from baseline in patients receiving losartan-based or atenolol-based therapy in the LIFE study.
LIFE was a randomized, double-blind trial comparing losartan-based and atenolol-based treatment regimens on the primary composite endpoint of death, myocardial infarction (MI), or stroke in 9193 patients aged 55-80 years with hypertension and left ventricular hypertrophy. Systolic and diastolic, pulse, and mean arterial pressures, blood pressure responder rates, distribution of open-label antihypertensive agents utilized, and the proportion of patients on randomized treatment were determined for each group at each clinic visit over a follow-up period of at least 4 years.
Overall blood pressure reductions were comparable in the losartan-based and atenolol-based treatment groups. The mean reductions in sitting trough systolic and diastolic blood pressures from baseline to the end of follow-up (or last visit before a primary endpoint event) were 30.2/16.6 mmHg in the losartan group and 29.1/16.8 mmHg in the atenolol group. The time-averaged difference in overall mean arterial pressure was similar between groups. The proportion of patients on individual dose combinations varied visit by visit but was generally comparable between groups. During the entire study, 56% (2579/4605) of losartan-treated patients received at least one dose of the combination of losartan 100 mg plus hydrochlorothiazide 12.5 mg and 51% of atenolol-treated patients received 100 mg of atenolol plus hydrochlorothiazide 12.5 mg at some time during the study.
Differences in blood pressure or distribution of add-on medications between treatment groups were not evident in the LIFE trial and, thus, cannot account for the observed outcome difference in the primary endpoint of risk reduction of the composite of cardiovascular death, stroke and MI favoring losartan.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Losartan, an angiotensin II receptor blocker (ARB), has been reported to promote sodium excretion and show an enhanced antihypertensive effect when used in combination with hydrochlorothiazide (HCTZ). We investigated the effects of losartan monotherapy and combination therapy together with HCTZ on cardiac function in hypertensive rats using echocardiography. Methods Spontaneously hypertensive rats (n = 21) fed on high-salt diet (8 % NaCl) for 13 weeks were randomly assigned to rats without medication (HS, n = 7), those medicated with ARB (ARB, losartan 30 mg/kg/day, n = 8), and those with ARB and HCTZ (ARB + HCTZ, losartan 30 mg/kg/day + HCTZ 10 mg/kg/day, n = 6). Blood pressure measurements and echocardiography were performed at 13, 17, and 29 weeks of age. After the end of the protocol, the proportion of cardiac muscle fibrosis was measured histologically. Results In the HS group, blood pressure and left ventricular mass/body weight (LV mass/BW) increased, and % fractional shortening (%FS) and early diastolic mitral annular velocity (e′) decreased significantly with age. In the ARB group, although blood pressure and %FS were maintained, LV mass/BW increased with age as in the HS group, and e′ decreased. In the ARB + HCTZ group, blood pressure decreased and LV mass/BW, %FS, and e′ were maintained. The progression of myocardial fibrosis was clearly prevented in rats treated with ARB. Conclusion ARB was shown to inhibit systolic disorder and myocardial fibrosis in hypertensive rats. Combination therapy proved to be more effective than monotherapy and is also effective in inhibiting diastolic disorders.
    Journal of Echocardiography 12/2012; 10(4). DOI:10.1007/s12574-012-0141-1
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A fixed-dose combination of losartan/hydrochlorothiazide (HCTZ) therapy may be a logical choice for antihypertensive treatment, including for initial therapy in patients with blood pressure elevation >20/10 mmHg above treatment target. The renin-angiotensin-aldosterone-system-activating effect of hydrochlorothiazide augments the efficacy of blocking the angiotensin II type 1 (AT1) receptor with losartan. Some adverse effects associated with hydrochlorothiazide, including increased risk for new-onset diabetes mellitus, may be offset by losartan. Losartan was frequently administered with hydrochlorothiazide in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, in which there was a 25% risk reduction for stroke in the losartan-based compared with the atenolol-based treatment group. The efficacy, tolerability, and convenience of losartan/HCTZ combination therapy may increase patient compliance and lower risk for stroke, a devastating outcome in patients with hypertension.
    Vascular Health and Risk Management 05/2007; 3(3):299-305.
  • [Show abstract] [Hide abstract]
    ABSTRACT: A series of urea analogues related to SA6817 and a GSK phosphonic acid with reported ACE inhibitory activity were prepared and tested for dual ACE and ECE activities. Although excellent ACE and NEP inhibition was achieved, only modest ECE inhibition was observed with one analogue.
    Bioorganic & medicinal chemistry letters 03/2008; 18(3):1058-62. DOI:10.1016/j.bmcl.2007.12.013 · 2.33 Impact Factor