Using fixed-dose combination therapies to achieve blood pressure goals

Hypertension affects an estimated 88 million Americans and is controlled to the recommended blood pressure (BP) goal of <140/90 mmHg in only 37% of individuals with hypertension. The benefits of achieving these goals, including significant reductions in cardiovascular morbidity and mortality, are well documented. Thus, a concerted effort to improve BP goal attainment is required. The majority of patients will require two or more antihypertensives to achieve BP goal. It has been shown that administering two drugs in a single-dose formulation substantially improves patient compliance compared with separate agent administration. Fixed-dose combination therapy can offer potential advantages over individual agents, including increased efficacy, reduced incidence of adverse effects, lower healthcare costs, and improved patient compliance through the use of a single medication administered once daily. Currently available fixed-dose agents include several combinations with complementary pharmacodynamic activity. This article reviews the fixed-dose antihypertensive combinations currently available in the US, and assesses the published literature comparing fixed-dose combinations with co-administration of two separate drugs or with other combinations. An analysis of the published literature between 1987 and 2007 reveals that most studies of fixed-dose antihypertensive combinations have compared the combination with monotherapy (53%); many fewer published papers have compared a fixed combination with coadministration of similar drugs as separate agents (2%), a fixed combination with another fixed combination from the same class (7%), or with a combination of agents from a different class (9%). Other comparisons have been with placebo, baseline or between generic formulations. This analysis indicates that: (i) physicians can be assured that a fixed-dose combination is more effective than either agent given as monotherapy; (ii) there is a paucity of data comparing different fixed-dose combinations; and (iii) very few studies have investigated the impact of fixed-dose combinations on achievement of BP goals, including both systolic BP and diastolic BP. For clinical decision making, physicians should rely on how the agents perform when administered together in add-on studies and how each component performs as monotherapy in reducing BP, achieving BP goals and reducing outcomes, as well as considering patient factors such as response to and tolerance of such agents as monotherapy and cost. The availability of effective and well tolerated fixed-dose combination antihypertensive agents should encourage primary-care physicians to be more willing to use such therapies in a timely manner when BP goals are not being achieved with monotherapy. This approach would improve BP control rates in the US and worldwide.