Experimental Study On The Antihypertensive Efficacy And Safety Of The Novel Renin Inhibitor Aliskiren

Objective: This study evaluates the antihypertensive efficacy and safety of the novel oral renin inhibitor aliskiren.Methods: The study was a randomized, double-blind, active-comparator trial in 118 patients with mild-to-moderate hypertension (mean sitting diastolic blood pressure [msDBP]≥90mmHg and<110mmHg). After a 2-week, single-blind placebo run-in, 109 patients (mean sitting diastolic blood pressure [msDBP]≥95mmHg and<110mmHg)were randomized to receive double-blind treatment with once-daily oral doses of aliskiren 300mg(n=28), 150mg(n=27), 75mg (n=26) or ramipril 5mg(n=28). The screening assessment included the change in msDBP and msSBP , responder rates (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 and multi- variate ANOVA . LSD was used for two groups'comparison. P value <0.05 was considered statistically significant.Results:1. 109 satisfied all inclusion criteria and were randomly assigned to study treatment. The distributions of gender, age, body mass index and medical histry were similar across the 4 treatment groups. Baseline blood pressure (BP) levels and the heart rate in the 4 groups were also similar.2. Drug Effects on BP(1) Aliskiren300, 150 and 75mg and ramipril 5mg significantly reduced msDBP from baseline (p<0.01). The mean change from baseline to end-of-treatment in blood pressure in the group treated with ramipril 5mg was found to differ from that of the group treated with aliskiren 300mg and 75mg (p<0.01), but not to differ significantly from the changes seen in the groups treated with aliskiren 150mg (p>0.05). The reductions in msDBP achieved with aliskiren 300mg were not different from those observed with aliskiren 150mg and 75mg at the week 8 end point(p>0.05).(2) Aliskiren 300, 150 and 75mg and ramipril 5mg significantly reduced msSBP from baseline (p<0.01). The mean change from baseline to end-of-treatment in blood pressure in the group treated with ramipril 5mg was found to differ from that of the group treated with aliskiren 300 mg (p<0.01), but not to differ significantly from the changes seen in the groups treated with aliskiren 150mg and 75mg (p>0.05). The reductions in msSBP achieved with aliskiren 300mg were significantly greater than those observed with aliskiren 150mg and 75mg at the week 8 end point(p<0.05).(3) Responder rates were higher with aliskiren 300mg (67.96%) than ramipril 5mg (53.76%,p<0.01) , aliskiren 150mg (62.01%, p>0.05) and aliskiren 75mg (60.14%, p>0.05 ), respectively. Responder rates with aliskiren 150mg and aliskiren 75mg were not significantly different from those observed with ramipril 5mg at the week 8 end point (p>0.05).3. Safety and Tolerability The incidence of adverse events in the 4 groups is similar(p>0.05). There were no serious adverse events during the study.Conclusion:1. Aliskiren 300 or 75 mg was superior to ramipril 5mg in reducing msDBP from baseline once a day.2. Aliskiren 300mg was superior to aliskiren 150mg or 75mg in reducing msSBP once a day.3. Responder rates with aliskiren 300mg once a day were significantly higher than ramipril 5mg and the proportion of patients defined as responders with aliskiren 300mg was higher than aliskiren 150mg or aliskiren 75mg once a day.4. Aliskiren 300, 150 and 75mg were well tolerated by patients with essential hypertension.There were no serious adverse events during the study.