Objective: To identify telmisartan doses that are more effective than placebo and non-inferior to hydrochlorothiazide (HCTZ) 12.5 mg, and are well tolerated, in lowering systolic blood pressure (SBP) in patients with isolated systolic hypertension (ISH).
Patients and methods: A 2-4-week single-blind placebo run-in was followed by randomization of 1039 patients (age 36-84 years) with ISH [seated SBP 150-179 mmHg and seated diastolic blood pressure (DBP) < 90 mmHg] to once-daily double-blind treatment with telmisartan 20, 40 or 80 mg, HCTZ 12.5 mg, or placebo. The change in seated trough SBP after 6 weeks compared with baseline was the primary end point. Secondary end points were the percentage achieving the target fall in SBP and the change from baseline in seated trough DBP. Incidence and severity of adverse events and physical examination and laboratory parameters were monitored for the safety evaluation.
Results: Baseline demographics in telmisartan 20 mg (n = 206), 40 mg (n = 210), 80 mg (n = 207), HCTZ 12.5 mg (n = 205) and placebo (n = 211) treatment groups were comparable: (mean +/- SD) age, 63.0 +/- 10.9 years; SBP, 162.9 +/- 8.1 mmHg; and DBP 83.4 +/- 5.0 mmHg. No previous antihypertensive therapy had been received by 66% of the patients. Mean reductions in seated trough SBP (adjusted for baseline and country) were: telmisartan 20 mg, 15.6 mmHg (n = 204); 40 mg, 17.9 mmHg (n = 209); and 80 mg, 16.9 mmHg (n = 205), compared with placebo, 11.4 mmHg (n = 208), and HCTZ 12.5 mg, 15.7 mmHg (n = 204). The target fall in seated trough SBP (< or =140 mmHg or reduction by > or =20 mmHg) was achieved in 46.6% (telmisartan 20 mg), 51.7% (telmisartan 40 mg), 53.9% (telmisartan 80 mg), 27.4% (placebo) and 42.7% (HCTZ 12.5 mg); the response rate was significantly higher for telmisartan 80 mg than for HCTZ 12.5 mg (P = 0.03). All-causality adverse events occurred in 19.9, 17.6 and 20.3% receiving telmisartan 20, 40 and 80 mg, respectively; 20.9% receiving placebo and 22.0% receiving HCTZ 12.5 mg. No drug-related serious adverse events occurred.
Conclusions: All doses of telmisartan (20-80 mg) were significantly superior to placebo in reducing SBP in patients with ISH and clinically comparable to HCTZ 12.5 mg. Tolerability of telmisartan was similar to that of placebo.