Combination therapy with AT(1)-receptor blockers

Although current hypertension management guidelines recommend increasingly stringent blood pressure targets, these targets are seldom achieved in clinical practice. Even in patients with mild-to-moderate hypertension, monotherapy is only effective in approximately 50-70% of patients, and thus there is a clear need for combination therapy if stringent blood pressure targets are to be achieved. Drugs used in combination therapy should satisfy a number of prerequisites, including complementary mechanisms of action, enhanced efficacy in combination, and maintained (or improved) tolerability. Evidence is accumulating that combination therapy with an AT(1)-receptor blocker and a diuretic represents a rational and effective treatment option. In clinical trials, the combination of candesartan cilexetil, 16 mg, and hydrochlorothiazide, 12.5 mg, has been shown to be more effective in lowering blood pressure than either agent alone. Furthermore, this combination has been shown to reduce blood pressure to a greater extent, and control blood pressure in a higher proportion of patients, than the combination of losartan, 50 mg, and hydrochlorothiazide, 12.5 mg, both when used instead of or in addition to previous antihypertensive therapy. The placebo-like tolerability of AT(1)-receptor blockers was maintained when these drugs were used in combination with hydrochlorothiazide. The combination of candesartan and a dihydropyridine calcium antagonist has also been shown to be more effective than either component alone. Furthermore, in the Candesartan and Lisinopril Microalbuminuria (CALM) Study, the combination of candesartan and lisinopril reduced blood pressure to a greater extent than either agent alone, and tended to have a greater effect on microalbuminuria.