Combination drug therapy in hypertension: a rational approach for the pharmacist

To review the use of combination therapy versus monotherapy in hypertension, and to review seven major antihypertensive combinations in regard to their pharmacologic actions and appropriateness.

Literature was identified through a MEDLINE search from January 1985 to December 1997. Search terms included hypertension, blood pressure, combination therapy, diuretics, beta-receptor antagonists, calcium channel antagonists, angiotensin-converting enzyme inhibitors (ACEIs). Major hypertension texts were also reviewed for information on combination therapy.

Clinical studies focusing primarily on blood pressure control with combinations of antihypertensive medications.

Data were evaluated with respect to study design, clinical outcomes, and use of antihypertensive classes commonly seen in practice.

Combination therapy in hypertension is often required because many patients cannot be controlled on one drug alone. Available data demonstrate that ACEIs plus diuretics or calcium channel blockers (CCBs) produce synergistic effects on blood pressure. Beta-blockers plus diuretics or CCBs produce additive effects, as does the rarer combination of diltiazem plus a dihydropyridine CCB. Ineffective combinations include beta-blockers plus ACEIs and dihydropyridine CCBs plus diuretics, although there are specific clinical circumstances where these combinations may be used.

When used appropriately, certain combinations of antihypertensives can effectively control blood pressure and minimize side effects. The pharmacist who understands and applies the pharmacology of these antihypertensives can help prescribers make rational decisions in selecting combination therapy.