Comparison of two- and three-drug combination therapy with candesartan in patients with severe hypertension

The efficacy and tolerability of two candesartan treatment regimens were evaluated in 578 severely hypertensive patients already receiving a diuretic plus an angiotensin-converting enzyme (ACE) inhibitor, a calcium channel blocker (CCB) or a beta blocker. Existing treatments were standardised during a two-week run-in period. Patients with uncontrolled blood pressure (diastolic blood pressure [DBP] > 90 mmHg) were randomly switched to a regimen comprising candesartan 16 mg plus hydrochlorothiazide (HCT) 12.5 mg once daily for four weeks (switch regimen, n=291), or had candesartan 8 mg once daily added to their existing treatment (add-on regimen, n=287). After four weeks’ treatment, mean sitting DBP was reduced from baseline by 11.2 mmHg (SD 11.2) and 13.9 mmHg (SD 11.5) in the switch and add-on treatment groups, respectively. Mean sitting SBP was decreased by 15.3 mmHg (SD 18.7) and 20.7 mmHg (SD 20.3), respectively. During an additional four weeks’ treatment, ‘switch’ non-responders had their doses of study medications doubled, resulting in a further reduction of 5.4 mmHg (SD 9.8) DBP and 5.9 mmHg (SD 14.9) SBP. Both treatment regimens were well tolerated. Thus, in patients with severe hypertension, adding candesartan to a standard-dose two-drug combination, or switching from a pre-existing two-drug, standard-dose combination to high-dose candesartan plus HCT enables enhanced BP control, with superiority of the three- over the two-drug combination.