Creating a combination antihypertensive regimen: what does the research show?

Major randomized clinical trials have demonstrated unquestionable clinical benefits of lowering blood pressure without establishing superiority of any specific antihypertensive medication. Most notably, these trials have indicated that a majority of patients with hypertension will require more than one drug to control blood pressure. The recognition that many patients with hypertension should receive a combination of two agents as initial therapy is reflected in current hypertension guidelines, including the recently published consensus statement by the Hypertension in African Americans Working Group (HAAWG) and the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7). In addition, there are some data that suggest that combination therapy may afford greater cardioprotection compared to monotherapy. For example, findings from A Lotrel Evaluation of Hypertensive Patients with Arterial Stiffness and Left Ventricular Hypertrophy (ALERT) indicated that low-dose combined angiotensin-converting enzyme inhibitor and calcium channel blocker antihypertensive treatment improved measures of cardiovascular structure and function compared with high-dose monotherapy with either component. Intuitive clinical wisdom suggests that some combinations of antihypertensive agents may provide enhanced clinical benefits; however, clinical trial data have not established optimal combination regimens. Thus, a challenging task for investigators is to determine which combination therapy regimens will provide the greatest cardiovascular benefits for patients with hypertension. A trial that is now in progress, Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH), directly compares cardiovascular mortality and morbidity rates for two preselected, fixed-dose combination therapies.