Efficacy and safety of initial combination therapy with amlodipine/valsartan compared with amlodipine monotherapy in black patients with stage 2 hypertension: the EX-STAND study

The strategy of initiating hypertension treatment with combination versus single-drug therapy was formally tested in a prospective, double-blind, parallel-group trial in blacks with stage 2 hypertension (mean sitting systolic BP (MSSBP) >= 160 and <200 mm Hg). Participants were randomized equally to amlodipine/valsartan (A/V) (n = 286) or amlodipine (A) monotherapy (n = 286). After 2 weeks, there was forced titration of A/V 5/160 mg to A/V 10/160 mg and of A 5 to A 10 mg followed by 10 additional weeks of treatment. If SBP was >= 130 mm Hg at week 4, the protocol allowed optional titration of A/V to the 10/320 mg dose and, at week 8, hydrochlorothiazide 12.5 mg was optionally added to both A/V and A if SBP >= 130 mm Hg. Amlodipine/valsartan at week 8 lowered MSSBP last observation carried forward significantly>A (33.3 vs 26.6 mm Hg, P<0.0001). Lowering of MSSBP with A/V significantly exceeded that of A in several specified subgroups-the elderly (>= 65 years), isolated systolic hypertension, and those with body mass index (BMI) >= 30 kg/m(2). More patients treated with A/V than A achieved BP control (<140/90 mm Hg) both at weeks 8 (49.8 vs 30.2%; P<0.0001) and 12 (57.2 vs 35.9%; P<0.0001). Both treatment regimens were well tolerated. In conclusion, the strategy of initiating combination antihypertensive drug therapy in blacks with stage 2 hypertension with amlodipine/valsartan achieves greater and quicker reductions in BP as well as significantly higher BP control rates than starting treatment with amlodipine monotherapy. Journal of Human Hypertension (2009) 23, 479-489; doi:10.1038/jhh.2008.153; published online 29 January 2009