Experimental Study On The Antihypertensive Efficacy And Safety Of The Fixed-dose Combination Of Valsartan/amlodipine

Objective: This study evaluates the antihypertensive efficacy and safety of the fixed-dose combination of valsartan/amlodipine.Methods: The study was a randomized, double-blind, active-comparator trial in 104 patients with mild-to-moderate hypertension, male 56,female 48, the average age was 51.4 (38-63). After stopping antihypertensive drug at least one week,the patients whose mean sitting diastolic blood pressure (msDBP) were≥95mmHg and<110mmHgcould enter single-blind period. After a 4-week, single-blind valsartan 80mg run-in, 85 patients (msDBP≥90mmHg and<110mmHg) were randomized to receive double-blind treatment with once-daily oral doses of valsartan 80mg (n=28), 160mg (n=29) or valsartan/amlodipine 80/5mg (n=28). The screening assessment included the change in msDBP and msSBP (mean sitting systolic blood pressure), effective power (msDBP <90mmHg and/or≥10mmHg reduction from baseline) and safety after 4 and 8 weeks. All data were managed by SPSS 13.0. Measurement data were expressed as mean士standard deviation. Statistical methods include repeated measurements ANOVA, one-way ANOVA and Paired t test. LSD was used for two groups'comparison. P value <0.05 was considered statistically significant.Results:1. 85 satisfied all inclusion criteria and were randomly assigned to study treatment. The distributions of gender, age, body mass index and medical history were similar across the 3 treatment groups. Baseline blood pressure (BP) levels and the heart rate in the 3 groups were also similar.2. Drug Effects on BP(1) At the baseline,the msDBP of three groups had no significant different (p=0.118).After 4 weeks, the msDBP of valsartan80mg, 160mg and valsartan/amlodipine 80/5mg had significantly declined from baseline (all p<0.01). The decline in msDBP of valsartan/amlodipine 80/5mg group was -9.07mmHg,which was significantly greater than valsartan 80mg and 160mg group (-2.53mmHg and -6.11mmHg, all p<0.05). After 8 weeks, the msDBP of valsartan/amlodipine 80/5mg group and valsartan 80mg group had no significantly difference with the 4th week (all p>0.05).But the msDBP of valsartan 160mg group were significant different from the 4th week (p<0.05). The decline in msDBP of valsartan/amlodipine 80/5mg group was -10.56mmHg, which was significantly greater than valsartan 80mg group (-3.13mmHg, p<0.05), but had no significantly difference with valsartan 160mg group (-9.00mmHg, p>0.05).(2) At the baseline, the msSBP of three groups had no significant different (p=0.143). After 4 weeks, the msSBP of valsartan80mg, 160mg and valsartan/amlodipine 80/5mg had significantly declined from baseline (all p<0.01). The decline in msSBP of valsartan/amlodipine 80/5mg group was -6.04mmHg,which was significantly greater than valsartan 80mg group (-2.16mmHg,p<0.01).However, the decline in msSBP of valsartan/amlodipine 80/5mg group had no significantly difference with valsartan 160mg group (-5.08mmHg,p>0.05).After 8 weeks, the msSBP of valsartan/amlodipine 80/5mg valsartan 160mg group were significant different from the 4th week (all p<0.05). The decline in msSBP of valsartan/amlodipine 80/5mg group had no significantly difference with valsartan 160mg group (-7.45mmHg and -6.72mmHg , p>0.05). The msSBP of valsartan 80mg group had no significantly difference with the 4th week (p>0.05). The decline in msSBP of valsartan/amlodipine 80/5mg group was -7.45mmHg, which was significantly greater than valsartan 80mg group (-2.53mmHg, p<0.01)(3) Effective power were higher with valsartan/amlodipine 80/5mg (82.14%) than valsartan 80mg (32.14%, p<0.01), but were similar to valsartan 160mg (68.97%, p>0.05)3. Safety and Tolerability:The incidence of adverse events in the 3 groups was similar (p>0.05). There were no serious adverse events during the study. Also there were no effect on laboratory indicators and heart rate during the study.Conclusion:1. Valsartan/Amlodipine 80/5mg was superior to valsartan 80mg in reducing msDBP and msSBP from baseline once a day, but was similar to valsartan 160mg. However, in regard to msDBP, valsartan/amlodipine 80/5mg could reach the maximum effect earlier than valsartan 160mg.2. Effective power with valsartan/amlodipine 80/5mg once a day were significantly higher than valsartan 80mg, but was similar to valsartan 160mg.3. Valsartan/Amlodipine 80/5mg was well tolerated by patients with essential hypertension. There were no serious adverse events during the study. Also there were no effect on laboratory indicators and heart rate during the study.