Combination Therapy for the Management of Hypertension: A Review of the Evidence

Purpose: Evidence regarding combination therapy for the management of hypertension is reviewed.

Summary: Numerous clinical trials have demonstrated the importance of early aggressive lowering of blood pressure, especially in patients at high cardiovascular risk. However, one of the difficulties with achieving these blood pressure goals quickly is that monotherapy is often insufficient. Many large randomized trials have shown that two or more antihypertensive agents are required for patients to reach their treatment goals. Recent data have suggested that the use of combination therapy in patients with hypertension may be beneficial in terms of improving blood-pressure-lowering efficacy, obtaining blood pressure goals earlier, and reducing major adverse cardiovascular events. Studies have found that therapy with a calcium channel blocker (CCB) combined with an angiotensin-converting-enzyme (ACE) inhibitor significantly reduces both blood pressure and major clinical events compared with an ACE inhibitor-diuretic combination. Combination ACE inhibitor-CCB therapy has also demonstrated superior blood-pressure-lowering efficacy and safety compared with either group used as monotherapy, including lower rates of peripheral edema compared with those achieved with increased doses of CCBs. The combination of an ACE inhibitor and an angiotensin II-receptor blocker has not been found to be superior to either group as monotherapy in patients with hypertension and should not be recommended at this time.

Conclusion: Combination drug therapy for the treatment of hypertension is supported by numerous randomized trials and clinical management guidelines. The addition of a diuretic or CCB to renin-angiotensin-aldosterone-system blocker therapy may provide an effective combination for reducing blood pressure and cardiovascular events.