Effectiveness of initiating treatment with valsartan/hydrochlorothiazide in patients with stage-1 or stage-2 hypertension

Abstract

This prospective, 6-week, multicenter, double-blind study examined the benefits of initiating treatment with combination valsartan/hydrochlorothiazide (HCTZ) compared with initial valsartan monotherapy for 648 patients with stage-1 or stage-2 hypertension (age=52.6+/-10 years; 54% male; baseline blood pressure (BP)=161/98 mm Hg, 32% stage 1). Patients were randomized to valsartan 80 mg (V-low), valsartan 160 mg (V-high) or valsartan/HCTZ 160/12.5 mg (V/HCTZ), and electively titrated after weeks 2 and 4 to the next dosage level (maximum dose valsartan/HCTZ 160/25 mg) if BP remained >140/90 mm Hg. At end of the study, patients initiated with V/HCTZ required less titration steps compared with the initial valsartan monotherapy groups (63 vs 86% required titration by study end, respectively) and reached the target BP goal of <140/90 mm Hg in a shorter period of time (2.8 weeks) (P<0.0001) vs V-low (4.3 weeks) and V-high (3.9 weeks). Initial combination therapy was also associated with higher BP control rates and greater reductions in both systolic and diastolic BP from baseline (63%, -27.7+/-13/-15.1+/-8 mm Hg) compared with V-low (46%, -21.2+/-13/-11.4+/-8 mm Hg, P<0.0001) or V-high (51%, -24.0+/-13/-12.0+/-10 mm Hg, P<0.01). Overall and drug-related AEs were mild to moderate and were similar between V/HCTZ (53.1 and 14.1%, respectively) and the two monotherapy groups, V-low (50.5 and 13.8%) and V-high (50.7 and 11.8%). In conclusion, initiating therapy with a combination of valsartan and low-dose HCTZ results in early, improved BP efficacy with similar tolerability as compared with starting treatment with a low or higher dose of valsartan for patients with stage-1 and stage-2 hypertension.

Trial registration: ClinicalTrials.gov NCT00280540.

Figure 1

Study design.

Figure 2

Patient disposition. V-low refers to patients initiated therapy with valsartan (80 mg); V-high refers to patients initiated therapy with valsartan (160 mg) and V/HCTZ refers to patients initiated with combination therapy. V/HCTZ, valsartan/hydrochlorothiazide.

Figure 3

Percentage of patients achieving the BP goal (<140/90 mm Hg). The primary efficacy time point was at week 4. At all weeks, 2, 4 and 6, the difference in the percentage of patients achieving BP control between the V/HCTZ and V-low (P<0.001) and between the V/HCTZ and V-high (P<0.05) groups was statistically significant. The difference between V-low and V-high was significant (P<0.001) only at week 4 but not at weeks 2 and 6. BP, blood pressure; V/HCTZ, valsartan/hydrochlorothiazide; V-high, valsartan 160 mg; V-low, valsartan 80 mg.

Figure 4

Change in (a) MSSBP (mm Hg) and (b) MSDBP (mm Hg) from baseline to week 6 of the double-blind treatment period. The primary efficacy time point was at week 4. At weeks 1, 2, 3, 4 and 6, the reduction in MSSBP and MSDBP was significantly greater in the V/HCTZ group as compared with the reductions observed in both V-low (P<0.001) and V-high groups (P<0.01). Reductions in MSSBP were significantly greater with V-high as compared with V-low only at weeks 3, 4 and 6 (P<0.001) and reductions in MSDBP were significantly greater with V-high as compared with V-low only at weeks 3 and 4 (P<0.001). BP, blood pressure; MSSBP, mean sitting systolic BP; MSSDP, mean sitting diastolic BP; V/HCTZ, valsartan/hydrochlorothiazide; V-high, valsartan 160 mg; V-low, valsartan 80 mg.

Figure 5

Mean time to BP goal defined as time (weeks) to achieving first treatment success (BP<140/90 mm Hg) in patients with stage-1 and stage-2 hypertension. P<0.05 for the V/HCTZ group as compared with the V-low and V-high group at week 6. BP, blood pressure; V/HCTZ, valsartan/hydrochlorothiazide; V-high, valsartan 160 mg; V-low, valsartan 80 mg.