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
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.
SourceAvailable from: onlinelibrary.wiley.com[Show abstract] [Hide abstract]
ABSTRACT: J Clin Hypertens (Greenwich). 2012;14:861-870. ©2012 Wiley Periodicals, Inc. Renal sympathetic denervation (RDN) is a novel treatment strategy for patients with resistant arterial hypertension. Recently, the Symplicity trials demonstrated significant peripheral blood pressure (BP) reduction. The present study aimed at measuring central aortic pressures and arterial stiffness as better predictors for cardiovascular risk in patients undergoing RDN. RDN was performed in 21 patients (systolic peripheral BP ≥150 mm Hg) with an Ardian/Medtronic (Mountain View, CA) ablation system. Data were recorded with an Arteriograph. After 6 months, peripheral systolic BP was reduced by 6.1% (P<.05) while central systolic pressure was reduced by 7.0% (P<.05). Subgroup analysis showed that in responders, peripheral systolic BP was reduced by 16.1% (P<.01) while central systolic pressure was reduced by 18.3% (P<.01). Arterial stiffness improved significantly. Aortic augmentation index (AIx) improved by 9.5% (P<.05). In responders, AIx improved by 19.2% (P<.02). Pulse wave velocity (PWV) was high at baseline (10.8 m/s) and improved by 10.4% (P<.05). In responders, PWV improved by 13.7% (P<.05). Multivariate analysis showed that short-term effects on PWV were BP-related, whereas during follow-up, improvement of PWV becomes BP-unrelated. RDN improves peripheral and central blood pressure as well as arterial stiffness and, thus, may improve cardiovascular outcome.Journal of Clinical Hypertension 12/2012; 14(12):861-70. DOI:10.1111/j.1751-7176.2012.00704.x · 2.96 Impact Factor
[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
[Show abstract] [Hide abstract]
ABSTRACT: Objective: To compare the effect of adding canrenone or hydrochlorothiazide (HCTZ) to valsartan/amlodipine combination on urinary albumin excretion (UAE) in microalbuminuric type 2 diabetic hypertensives. Research design and methods: After a 2-week placebo period and after 4 weeks of valsartan 160 mg plus amlodipine 5 mg combination, 120 patients whose blood pressure (BP) was not controlled (> 130/80 mmHg) were randomized to canrenone 25 mg or HCTZ 12.5 mg in addition to the previous therapy for 24 weeks. After the first 6 weeks of triple therapy, canrenone or HCTZ doses were doubled in the patients whose BP was yet uncontrolled. At the end of each period (placebo, dual combination and triple combination therapy), clinic and ambulatory BP measurements were recorded and 24 h UAE was evaluated. Results: Both triple combinations produced greater clinical and ambulatory BP reduction than dual therapy, with no difference between the two groups. UAE was reduced by both regimens, but the decrease associated with canrenone add-on therapy was more pronounced. At week 24, UAE decreased by 45.3% in the canrenone group and by 20.3% in the HCTZ group (p < 0.01). Conclusions: These findings indicate that, despite similar BP-lowering effect, the addition of canrenone to valsartan/amlodipine combination was more effective in reducing UAE than HCTZ addition.Expert Opinion on Pharmacotherapy 01/2014; DOI:10.1517/14656566.2014.874415 · 3.09 Impact Factor