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.