Antihypertensive Efficacy Of Losartan Research Articles

Antihypertensive efficacy of angiotensin receptor blockers as monotherapy as evaluated by ambulatory blood pressure monitoring: a meta-analysis

Angiotensin receptor blockers (ARBs) are available in different dosages and it is common clinical practice to uptitrate if blood pressure goal is not achieved with the initial dose. Data on the incremental antihypertensive efficacy with uptitration are scarce. It is also unclear if antihypertensive efficacy of losartan is comparable with other ARBs. We systematically reviewed PubMed/EMBASE/Cochrane databases for all randomized clinical trials until December 2012 reporting 24 h ambulatory blood pressure (ABP) for most commonly available ARBs in patients with hypertension. Reduction in ABP with ARBs was evaluated at 25% of the maximum (max) dose, 50% of the max dose, and at the max dose. Comparison was made between 24 h BP-lowering effect of losartan 50 and 100 mg and other ARBs at 50% max dose and the max dose, respectively. Sixty-two studies enrolling 15 289 patients (mean age 56 years; 60% men) with a mean duration of 10 weeks were included in the analysis. Overall, the dose-response curve with ARBs was shallow with decrease of 10.3/6.7 (systolic/diastolic), 11.7/7.6, and 13.0/8.3 mmHg with 25% max dose, 50% max dose, and with the max dose of ARBs, respectively. Losartan in the dose of 50 mg lowered ABP less well than other ARBs at 50% max dose by 2.5 mmHg systolic (P < 0.0001) and 1.8 mmHg diastolic (P = 0.0003). Losartan 100 mg lowered ABP less well than other ARBs at max dose by 3.9 mm Hg systolic (P = 0.0002) and 2.2 mmHg diastolic (P = 0.002). In this comprehensive analysis of the antihypertensive efficacy of ARBs by 24 h ABP, we observed a shallow dose-response curve, and uptitration marginally enhanced the antihypertensive efficacy. Blood pressure reduction with losartan at starting dose and at max dose was consistently inferior to the other ARBs.

Pharmacokinetics, Safety, and Antihypertensive Efficacy of Losartan in Combination with Hydrochlorothiazide in Hypertensive Patients with Renal Impairment

The pharmacokinetics and pharmacodynamics of 7 days of treatment with losartan 50 mg/hydrochlorothiazide 12.5 mg were evaluated in 14 patients with normal renal function and in 12 patients with mild to moderate renal impairment. The efficacy of losartan 50 mg/hydrochlorothiazide 12.5 mg titrated to losartan 100 mg/hydrochlorothiazide 25 mg was examined in 32 hypertensive patients with mild to moderate renal impairment who were treated for 12 weeks. Safety was assessed in both studies by the incidence of adverse experiences. After 7 days of treatment, the AUC for losartan, E-3174, and hydrochlorothiazide was slightly higher in patients with mild to moderate renal impairment, but the reduction in blood pressure (BP) after 7 days was not different between the two groups. The final (week 12) mean reductions in trough sitting diastolic and systolic BP were 15.0 ± 7.1 mmHg (p < 0.01) and 20.8 ± 16.7 mmHg (p < 0.01), respectively. There were no observed increases in drug-related adverse experiences in either study. Overall, the combination of losartan/hydrochlorothiazide was effective in lowering blood pressure and was well tolerated in patients with mild to moderate renal impairment.

Pharmacokinetics, Safety, and Antihypertensive Efficacy of Losartan in Combination with Hydrochlorothiazide in Hypertensive Patients with Renal Impairment

The pharmacokinetics and pharmacodynamics of 7 days of treatment with losartan 50 mg/hydrochlorothiazide 12.5 mg were evaluated in 14 patients with normal renal function and in 12 patients with mild to moderate renal impairment. The efficacy of losartan 50 mg/hydrochlorothiazide 12.5 mg titrated to losartan 100 mg/hydrochlorothiazide 25 mg was examined in 32 hypertensive patients with mild to moderate renal impairment who were treated for 12 weeks. Safety was assessed in both studies by the incidence of adverse experiences. After 7 days of treatment, the AUC for losartan, E-3174, and hydrochlorothiazide was slightly higher in patients with mild to moderate renal impairment, but the reduction in blood pressure (BP) after 7 days was not different between the two groups. The final (week 12) mean reductions in trough sitting diastolic and systolic BP were 15.0 +/- 7.1 mmHg (p < 0.01) and 20.8 +/- 16.7 mmHg (p < 0.01), respectively. There were no observed increases in drug-related adverse experiences in either study. Overall, the combination of losartan/hydrochlorothiazide was effective in lowering blood pressure and was well tolerated in patients with mild to moderate renal impairment.

Angiotensin II antagonists for hypertension: are there differences in efficacy?

We compared the antihypertensive efficacy of available drugs in the new angiotensin-II-antagonist (AIIA) class. The antihypertensive efficacy of losartan, valsartan, irbesartan, and candesartan was evaluated from randomized controlled trials (RCT) by performing a metaanalysis of 43 published RCT. These trials involved AIIA compared with placebo, other antihypertensive classes, and direct comparisons between AIIA. A weighted-average for diastolic and systolic blood pressure reduction with AIIA monotherapy, dose titration, and with addition of low-dose hydrochlorothiazide (HCTZ) were calculated. Weighted-average responder rates were also determined. The metaanalysis assessed a total of 11,281 patients. The absolute weighted-average reductions in diastolic (8.2 to 8.9 mm Hg) and systolic (10.4 to 11.8 mm Hg) blood pressure reductions (not placebo-corrected) for AIIA monotherapy were comparable for all AIIA. Responder rates for AIIA monotherapy were 48% to 55%. Dose titration resulted in slightly greater blood pressure reduction and an increase in responder rates to 53% to 63%. AIIA/hydrochlorothiazide combinations produced substantially greater reduction in systolic (16.1 to 20.6 mm Hg) and diastolic (9.9 to 13.6 mm Hg) blood pressure reductions than AIIA monotherapy and responder rates for AIIA/HCTZ combinations were 56% to 70%. This comprehensive analysis shows comparable antihypertensive efficacy within the AIIA class, a near-flat AIIA-dose response when titrating from starting to maximum recommended dose, and substantial potentiation of the antihypertensive effect with addition of HCTZ.

Tolerability and Antihypertensive Efficacy of Losartan vs Captopril in Patients with Mild to Moderate Hypertension and Impaired Renal Function

Objective: This international, multicentre, 16-week, double-blind, parallel, two-arm, randomised study was conducted to compare the effects on blood pressure and tolerability of the angiotensin II (Ang II) AT1 receptor antagonist losartan and captopril in patients with mild to moderate hypertension and impaired renal function. Patients: 102 of the total of 129 patients (mean age 55.2 years) having any form of secondary hypertension except renal artery stenosis were recruited from 18 centres in 10 countries. Mild hypertension was defined as a sitting diastolic blood pressure (SiDBP) of 95 to 105mm Hg, moderate hypertension as 106 to 115mm Hg, while creatinine clearance was required to be in the range of 20 to 60 ml/min/1.73m2. Interventions: The initial 4-week placebo period was followed by 12 weeks of treatment with losartan 50mg, possibly titrated to 100mg, once daily (group 1, n = 64) or 25mg captopril, possibly titrated to 50mg, twice daily (group 2, n = 65). Main Outcome Measures: Antihypertensive efficacy was evaluated by the reduction of blood pressure (BP) after 12 weeks. The main efficacy measurement was the SiDBP. Secondary end-points included sitting systolic and standing BP, creatinine clearance, total proteinuria, total cholesterol, triglycerides and high density lipoprotein cholesterol levels. Tolerability was assessed by the incidence of adverse events and by clinical and laboratory tolerability measurements. Results: After 12 weeks’ administration of losartan a reduction of 12.2 ± 10.2mm Hg in SiDBP and 15.5± 18.0mm Hg in sitting systolic blood pressure (SiSBP) was observed, compared with 11.2± 11.4mm Hg and 15.6± 20.6mm Hg, respectively, in captopril-treated patients. Thus, there was no statistically significant difference between the two groups, which was also consistent with the other parameters recorded. In the losartan group, total proteinuria was significantly decreased at the end of the study. Creatinine clearance, lipids and the proportion of patients with clinical adverse experiences showed no remarkable changes at all in the two groups, although such experiences affecting the respiratory system, especially cough, appeared significantly more often (p < 0.034) in captopril-treated patients. Conclusions: Losartan could be as suitable as captopril as an antihypertensive agent in cases where renal function is impaired.

E099 A randomized, double-blind, parallel study of the safety and antihypertensive efficacy of losartan vs amlodipine in patients with mild to moderate hypertension and impaired renal function

E099 A randomized, double-blind, parallel study of the safety and antihypertensive efficacy of losartan vs amlodipine in patients with mild to moderate hypertension and impaired renal function

The discovery and development of angiotensin II antagonists.

During the development of losartan, various issues arose that could have stopped losartan and hampered the successful development of the angiotensin II antagonists in general. Some of these issues were real problems that had to be solved if losartan was to advance, such as the need for a commercially viable synthesis. Other issues, such as whether EXP3174 would form in humans, were anticipated as potential problems that should be addressed. Because of the combined efforts of discovery and development groups at DuPont, and later at Merck and DuPont Merck, the development of losartan was rapid. While some people were working to answer questions such as the antihypertensive efficacy of losartan in humans as quickly as possible, other people were searching for potential backups to losartan. Without an efficient integration of Discovery and Development efforts, the commercially successful development of any drug would be threatened, and it helped to give losartan a critical 2-year lead on the most advanced competitive Ang II antagonists.

Efficacy and safety of losartan in hypertensive patients with side effects induced by other antihypertensive agents

In an open-label trial, 54 patients with hypertension (22 men and 32 women, aged 42 to 67 years [mean age, 54 ± 16 years]), who had discontinued therapy with calcium channel blockers (group 1, n = 15) or angiotensin-converting enzyme (ACE) inhibitors (group 2, n = 39) after 30 to 40 days because of peripheral edema or dry cough, respectively, were treated with losartan 50 mg/d orally for 30 days. Mean baseline values for sitting systolic and diastolic blood pressures and heart rate were 164.3 ± 4.9 mm Hg, 102.3 ± 5.4 mm Hg, and 67.0 ± 6.5 beats/min, respectively, in group 1, and 162.6 ± 7.9 mm Hg, 101.3 ± 4.6 mm Hg, and 68.2 ± 6.1 beats/min, respectively, in group 2. Losartan treatment was continued for 6 months, and all 54 patients completed the study. Losartan reduced blood pressure levels to 136.6 ± 10.8/85.0 ± 6.2 mm Hg in group 1 and 136.5 ± 8.9/80.6 ± 7.0 mm Hg in group 2 after 30 days of treatment, without evidence of changes in heart rate. The antihypertensive efficacy of losartan was similar to that observed at the end of the initial therapy with calcium channel blockers (138.3 ± 8.9/83.6 ± 5.1 mm Hg) or ACE inhibitors (136.7 ± 5.5/80.4 ± 7.8 mm Hg). Clinical side effects associated with losartan therapy were minimal, and hematologic and biochemical profiles were not altered by the drug. Only two patients exhibited mild dizziness, which disappeared during the trial. Results of this study indicate that losartan is an effective, well-tolerated drug for the treatment of essential hypertension, especially in patients with reduced tolerance to calcium channel blockers or ACE inhibitors.