Fixed-dose combinations of renin-angiotensin blocking agents with calcium channel blockers or hydrochlorothiazide in the treatment of hypertension

Hypertension is a health threat which, so far, is not successfully managed, despite the availability of effective drug treatment. Guidelines recommend drug-drug combinations as a first-line treatment in high-risk patients with severe hypertension, or as an escalation for patients not controlled on monotherapy. Blockers of the renin-angiotensin system (RAS) are usually the basis for such treatment. Both calcium channel blockers (CCBs) and hydrochlorothiazide (HCTZ) are recommended partners. There is only one end point study comparing different combinations. ACCOMPLISH compared a combination of benazepril with either amlodipine or HCTZ in patients with compelling indications for CCBs. The primary end point of cardiovascular morbidity and mortality was reduced by 20% in the benazepril/CCB arm, as were selected secondary end points. Side effects were generally more frequent with CCB than with the thiazide combinations. However, no comparative study of the ACCOMPLISH type exists for patients with compelling indications for thiazides. In summary, the evidence indicates that angiotensin converting enzyme inhibitor (ACEi)/CCB combinations are more effective in selected high-risk patients with compelling indications for the use of CCBs than are ACEi/HCTZ combinations. Side effects offset these data, and compelling indications may have favored the outcomes. Comparisons in a more unselected patient population are needed to define the role of particular drug-drug combinations.