Combination therapy with Renin-Angiotensin-aldosterone receptor blockers for hypertension: how far have we come?

Abstract

In a large number of patients with hypertension, > or =2 antihypertensive agents are required to achieve blood pressure (BP) goals. There is good rationale for initial combination therapy based on clinical trials demonstrating that achievement of BP goals within a reasonably short period of time results in fewer cardiovascular events. One approach to attaining BP goals and improving medication adherence is fixed-dose combination therapy, the use of which dates back to the 1960s. Given some of the advantages of renin-angiotensin-aldosterone system (RAAS) blockers in patients with heart disease, kidney disease, and diabetes, many combinations include either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. In most studies, however, thiazide diuretics were necessary to achieve goal BP. Calcium channel blockers have also been used in combination with angiotensin-converting enzyme inhibitors to lower BP. Studies are now under way to determine the relative benefits of an RAAS blocker/diuretic compared with an RAAS blocker/calcium channel blocker as initial therapy.

Figure 1

Percentage of all participants in whom target blood pressure (BP) (<130/85 mm Hg) was achieved by week and treatment group (intent‐to‐treat population). *If the maximum dosage regimens did not reduce BP to target level, hydrochlorothiazide (HCTZ) 12.5 mg/d was added at week 8 (so that weeks 10 and 12 reflect diuretic add‐on therapy). Reproduced from Bakris and Weir ⁹ with permission from Blackwell Publishing.

Figure 2

Increases in ankle‐foot volume (AFV) associated with amlodipine and amlodipine/valsartan combination therapy. The thick line is the median value, the upper and lower limits of the rectangle correspond to the standard deviation, and the narrow columns correspond to the upper and lower range limits. *P<.01 vs amlodipine. Adapted with permission from Fogari et al. ⁴⁸