Amlodipine/valsartan 5/160 mg versus valsartan 160 mg in Chinese hypertensives.

BACKGROUND: A majority of hypertensives require treatment with ≥2 antihypertensive therapies to achieve blood pressure (BP) goals. Single-pill combinations (SPC) may improve convenience and adherence to therapy and reduce health care resource use and costs. The antihypertensive effects of amlodipine and valsartan are well established. This study evaluated the efficacy and safety of amlodipine/valsartan 5/160 mg SPC for the treatment of hypertension in predominantly Chinese patients not adequately controlled on valsartan 160 mg alone. METHODS: In this multicentre study (24 centres), adults with stage 1 or 2 hypertension not adequately controlled with valsartan monotherapy were randomised to receive double-blind amlodipine/valsartan 5/160 mg SPC or valsartan 160 mg once daily for 8 weeks. RESULTS: The least-square mean change (standard error) from baseline to endpoint in mean sitting diastolic blood pressure (MSDBP) at trough, the primary efficacy variable, was -10.3 (0.39) mm Hg with amlodipine/valsartan and -6.6 (0.40) mm Hg with valsartan (difference: -3.7 [0.54] mm Hg, p<0.0001). The corresponding results for mean sitting systolic blood pressure (MSSBP) were -14.9 (0.61) mm Hg and -7.0 (0.61) mm Hg, respectively (difference: -7.9 [0.84] mm Hg, p<0.0001). A significantly greater proportion of patients achieved overall BP control (MSSBP/MSDBP<140/90 mm Hg) with combination therapy (61.3%) versus monotherapy (39.3%; p<0.0001). Both treatments were well tolerated. CONCLUSION: Amlodipine/valsartan 5/160 mg SPC is a safe and effective therapy for lowering BP in predominantly Chinese adults with stage 1 or 2 hypertension not adequately controlled with valsartan 160 mg monotherapy.

Efficacy and safety of valsartan compared to enalapril in hypertensive children: a 12-week, randomized, double-blind, parallel-group study.

OBJECTIVE: This study compares efficacy and safety of valsartan with enalapril in hypertensive children aged 6-17 years. METHOD: This was a 12-week, randomized, double-blind, parallel-group, active-controlled study. After a single-blind placebo run-in period (4-28 days), patients with mean sitting systolic blood pressure (BP) (MSSBP) at least 95th percentile for age, gender, and height were randomized to receive half the assigned dose for first week, and force-titrated to full dose for 11 weeks (≥18 to <35 kg - valsartan: 80 mg, enalapril: 10 mg; ≥35 to <80 kg - valsartan: 160 mg, enalapril: 20 mg; ≥80 to ≤160 kg - valsartan: 320 mg, enalapril: 40 mg). The primary efficacy variable was changed from baseline in MSSBP to show noninferiority of valsartan to enalapril. Other efficacy variables were changed from baseline in MSDBP, SBP control rate, and 24-h ambulatory BP parameters. RESULTS: Of 300 randomized patients, 281 (94%) completed the study. At week 12, MSSBP reductions were similar for valsartan and enalapril (primary endpoint of noninferiority, P < 0.0001). Least square mean BP reductions from baseline of -15.4/-9.4 mmHg were observed for valsartan compared with -14.1/-8.5 mmHg for enalapril. A similar proportion of patients achieved SBP control (valsartan: 67%; enalapril: 70%). In the subset of patients who underwent ambulatory BP assessments, valsartan provided greater reductions than enalapril in mean 24-h SBP (valsartan: -9.8 mmHg, enalapril: -7.2 mmHg: P = 0.03). The overall incidence of AEs was similar (valsartan 60%, enalapril 58%) with headache, cough, and nasopharyngitis reported most frequently. CONCLUSIONS: Valsartan and enalapril provided comparable BP reductions and effective BP control and were well tolerated in hypertensive children aged 6-17 years.

Efficacy and tolerability of combination therapy with valsartan/hydrochlorothiazide in the initial treatment of severe hypertension.

OBJECTIVE: Most patients with severe hypertension are at high risk for cardiovascular events and require prompt blood pressure (BP)-lowering and combination therapy to achieve BP goals. This study evaluated the therapeutic efficacy and tolerability of initial treatment with the combination of valsartan and hydrochlorothiazide (HCTZ) compared with valsartan monotherapy in patients with severe hypertension. RESEARCH DESIGN AND METHODS: This was a 6-week, randomized, double-blind, multicenter, forced titration study that compared initial therapy with the combination of valsartan/HCTZ 160/12.5 mg (force titrated to 160/25 mg after 2 weeks and to 320/25 mg after 4 weeks) to monotherapy with valsartan 160 mg (force titrated to 320 mg after 2 weeks and sham-titrated to 320 mg after 4 weeks). Eligible patients were 18-80 years old with severe essential hypertension (mean sitting diastolic BP > or = 110 mmHg and < 120 mmHg and mean sitting systolic BP > or = 140 mmHg and < 200 mmHg). The Clinical Trial Registry number was NCT00273299. MAIN OUTCOME MEASURES: The primary efficacy variable was the rate of BP control (mean sitting BP < 140/90 mmHg) at Week 4. Tolerability was evaluated by monitoring all adverse events, vital signs, and laboratory tests including hematology and biochemistry. RESULTS: A total of 608 patients were randomized to either valsartan/HCTZ (n = 307) or valsartan monotherapy (n = 301). Significantly more patients achieved overall BP control (< 140/90 mmHg) with valsartan/HCTZ compared to monotherapy at Week 4 (primary efficacy variable and timepoint) (39.6% vs. 21.8%; p < 0.0001) and Week 6 (48.2% vs. 27.2%; p < 0.0001). Mean reductions in BP at Week 4 were significantly greater for valsartan/HCTZ (30.8/22.7 mmHg vs. 21.7/17.5 mmHg; p < 0.0001), with further reductions at Week 6. BP control rates were greater with combination therapy as early as Week 2. The overall incidence of adverse events was comparable between the combination therapy (34.9%) and monotherapy (36.7%) treatment groups. A potential limitation of the forced-titration design is that some patients were titrated to higher doses despite having achieved goal BP. This may impact the interpretation of the incidence of dose-dependent adverse events. CONCLUSIONS: Initial therapy with valsartan/HCTZ is effective and well tolerated in patients with severe hypertension.