Amlodipine/valsartan fixed-dose combination treatment in the management of hypertension: A double-blind, randomized trial

Abstract

Background: To compare the fixed-dose combination (FDC) of amlodipine/valsartan 5/80 mg with valsartan 160 mg monotherapy for efficacy and safety in hypertensive patients.

Methods: We designed this double-blind, randomized, and noninferiority trial in which patients with elevated systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) were randomly assigned to receive amlodipine/valsartan 5/80 mg FDC or valsartan 160 mg monotherapy for 8 weeks. The primary endpoint was changes in office SBP and DBP from baseline to 8 weeks. Twenty-four-hour blood pressure (BP) and the incidence of adverse events were recorded.

Results: A total of 42 patients underwent randomization. At 8 weeks, office SBP changes were -16.5 ± 15.5 mmHg (p < 0.001) with amlodipine/valsartan 5/80 mg FDC and -6.9 ± 11.4 mmHg (p = 0.012) with valsartan 160 mg monotherapy while corresponding changes in office DBP were -9.8 ± 7.7 mmHg (p < 0.001) and -2.5 ± 6.6 mmHg (p = 0.095), respectively. The between-group differences were -9.6 mmHg (95% CI, -18.1 to -1.1; p = 0.028) for SBP and -7.3 mmHg (95% CI, -11.8 to -2.8; p = 0.002) for DBP. Furthermore, reductions in both 24-hour SBP (-9.2 mmHg; 95% CI, -16.4 to -2.1; p = 0.013) and DBP (-4.6 mmHg; 95% CI, -9.2 to -0.1; p = 0.048) were consistently greater with amlodipine/valsartan 5/80 mg FDC than with valsartan 160 mg. Overall, 27 and 23 adverse events occurred in the amlodipine/valsartan 5/80 mg FDC group and in the valsartan 160 mg monotherapy group, respectively. The majority were mild and were not related to study medications. There were no significant differences in safety between two treatments.

Conclusion: Efficacy of amlodipine/valsartan 5/80 mg FDC was superior to that of valsartan 160 mg monotherapy while both treatments were well-tolerated.

Fig. 1

Study scheme. FDC = fixed-dose combination.

Fig. 2

Flow diagram. ABPM = ambulatory blood pressure monitoring; AE = adverse event; FDC = fixed-dose combination; ITT = intention to treat.

Fig. 3

Changes in office BP from baseline to 8 wks. In the intention-to-treat population, office BP was reduced from 150.3 ± 12.9/92.1 ± 10.8 mmHg to 133.8 ± 14.6/82.3 ± 8.7 mmHg in the amlodipine/valsartan FDC group and from 141.1 ± 12.7/90.0 ± 9.4 mmHg to 134.3 ± 12.7/87.5 ± 9.5 mmHg in the valsartan monotherapy group. There were greater reductions in office BP in the amlodipine/valsartan FDC group than in the valsartan monotherapy group (A). In the per-protocol population, office BP was reduced from 150.3 ± 12.9/92.1 ± 10.8 mmHg to 133.8 ± 14.6/82.3 ± 8.7 mmHg in the amlodipine/valsartan FDC group and from 140.5 ± 14.0/88.8 ± 9.2 mmHg to 133.3 ± 13.8/85.8 ± 8.1 mmHg in the valsartan monotherapy group. There were consistently greater reductions in office BP in the amlodipine/valsartan FDC group than in the valsartan monotherapy group (B). BP = blood pressure; FDC = fixed-dose combination.

Fig. 4

Changes in mean 24-h BP by ambulatory BP monitoring from baseline to 8 wks. Mean BP was reduced by –14.7 ± 11.6/–7.7 ± 7.4 mmHg in the amlodipine/valsartan FDC group and by –5.5 ± 11.4/–3.0 ± 7.2 mmHg in the valsartan monotherapy group. There were significantly greater reductions in both mean 24-h systolic and diastolic BP in the amlodipine/valsartan FDC group than in the valsartan monotherapy group. BP, blood pressure; FDC = fixed-dose combination.