Clinical aspects of combination therapy

The failure of monotherapy to provide adequate blood pressure control is one of the most important rationales for combination therapy. Other factors associated with inadequate control include noncompliance, side effects, and the reluctance of physicians to treat early enough or aggressively enough. Findings from multiple studies, which have demonstrated that many patients require more than 1 drug to control blood pressure, have led to 3 treatment strategies: maximal dose monotherapy, substitution monotherapy, and combination therapy. Each strategy has its advantages and disadvantages. As suggested by one study, combination therapy also appears to reduce cardiovascular endpoints in patients with hypertension and diabetes when compared monotherapy. There are 3 strategies for combination therapy. The first is to titrate each component and then use-a fixed-dose combination that includes the same doses of both agents once the appropriate dose of both agents is reached. The second is to start with a single agent and then use a fixed-dose combination that includes a second agent and the same dose of the first agent if blood pressure is not adequately controlled. The third is to initiate therapy with a fixed-dose combination and then titrate the combination upward as necessary. Four combinations are currently available in the United States to treat hypertension: a beta blocker plus a thiazide; an angiotensin-converting enzyme (ACE) inhibitor plus a thiazide; an angiotensin receptor blocker plus a diuretic; and a calcium channel blocker plus an ACE inhibitor. Studies evaluating these combinations have shown that they provide better blood pressure control than when either of their components is given alone.