Moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy

Objectives Many angiotensin receptor blocker (ARB) monotherapy patients need at least two agents to control blood pressure (BP). We investigated whether initiating intensive treatment with combination amlodipine/valsartan was superior to moderate treatment with amlodipine/valsartan in patients previously uncontrolled on ARB monotherapy. Methods In this 12-week study, patients aged at least 18 years on ARB (other than valsartan) for at least 28 days (with treatment-naive patients or those not controlled on agents other than an ARB treated with open-label olmesartan 20 or 40 mg, respectively, for 28 days) and with uncontrolled mean sitting systolic blood pressure (MSSBP; >-150-<200mmHg) were randomized to amlodipine/valsartan 5/320mg (n=369) or 5/160mg (n=359). At week 2, the dose was increased to 10/320mg in the intensive arm. Hydrochlorothiazide 12.5mg was added to both arms at week 4. Optional up-titration with hydrochlorothiazide 12.5mg at week 8 was allowed if MSSBP was more than 140mmHg. Results At baseline, mean office sitting BP was comparable in the intensive (163.9/95.5mmHg) and moderate (163.3/95.0mmHg) groups. Intensive treatment provided greater BP reductions versus moderate treatment (P<0.05) from week 4 (-23.0/-10.4 versus -19.2/-8.7mmHg; primary endpoint) to week 12 (-29.0/-14.8 versus -25.3/-12.3 mmHg). Adverse events were reported by a similar percentage of patients in both groups (36.3% intensive, 37.6% moderate); peripheral edema was more common with intensive versus moderate treatment (8.7 versus 4.5%; P=0.025). Conclusions Initiating treatment with an intensive dose of amlodipine/valsartan provides significantly greater BP lowering versus moderate treatment in hypertensive patients unresponsive to ARB monotherapy. Both treatment regimens were generally well tolerated based on adverse event reports, but the lack of routine laboratory testing after screening limits conclusions on tolerability. J Hypertens 29:161-170 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.