Blood pressure control with angiotensin receptor blocker-based three-drug combinations: key trials

Most hypertensive patients only achieve blood pressure (BP) control with a combination of antihypertensive drugs from different classes and many require three or more drugs. Two three-drug, fixed-dose combinations are available: (1) the angiotensin receptor blocker (ARB), valsartan (VAL), the calcium channel blocker, amlodipine (AML), and the diuretic, hydrochlorothiazide (HCTZ); (2) the ARB, olmesartan medoxomil (OLM), AML, and HCTZ.

This article reviews two clinical studies in patients with moderate-to-severe hypertension, which compared the efficacy and safety of VAL/AML/HCTZ and OLM/AML/HCTZ with the component two-drug combinations.

Each triple combination produced significantly greater reductions in seated systolic/diastolic BP and higher BP control rates than the two-drug combinations. Subgroup analyses showed that BP reductions and control rates with the three-drug combinations were unaffected by age, gender, race, and hypertension severity (VAL/AML/HCTZ and OLM/AML/HCTZ), and that efficacy was maintained for up to 52 weeks (OLM/AML/HCTZ). OLM/AML/HCTZ and VAL/AML/HCTZ also produced significantly larger reductions in ambulatory systolic and diastolic BP over 24 hours, the daytime, and nighttime compared with two-drug combinations. Adverse events were mainly of mild or moderate intensity and each threedrug combination was well tolerated.

ARB/AML/HCTZ combinations produce BP reductions and control rates superior to two-drug combinations and may help difficult-to-treat patients to achieve BP control.