The safety of adding carvedilol to hypertensive patients inadequately treated with diuretics

Summary

A single-blind, single-center study was conducted to investigate the short-term safety and efficacy of carvedilol, a new cardiovascular agent, when added to 25 mg hydrochlorothiazide (HCTZ) as combination therapy for patients inadequately treated with HCTZ alone. A total of 18 patients entered the baseline study phase, during which they received 25 mg HCTZ once daily for 4 weeks; 16 of these patients (8 men and 8 women) entered the combination treatment phase. All patients had a supine diastolic blood pressure (DBP) of ≥ 95 mm Hg prior to receiving the first dose of combination treatment. Combination treatment consisted of 25 mg HCTZ plus 12.5 mg carvedilol once daily for 2 days, followed by a forced titration of the carvedilol dose to 25 mg for 7 days. After 2 days of 12.5 mg carvedilol plus 25 mg HCTZ once daily, mean trough blood pressure was reduced as compared with baseline values. Of 16 patients, 6 (38%) achieved a trough supine DBP of < 90 mm Hg. After 1 additional week of combination therapy with 25 mg carvedilol, 8 of 15 patients (53%) achieved a trough supine DBP of < 90 mm Hg and 14 of 15 patients (93%) achieved that of < 95 mmHg. At each visit during the combination treatment phase, the acute reduction in blood pressure was greatest during the first 2 h after dosing. The heart rate was minimally affected by combination treatment with carvedilol at either trough levels or acutely after dosing. Nine patients experienced adverse events during combination treatment. One patient withdrew because of dizziness and fatigue. In conclusion, at an initial dose of 12.5 mg once daily, carvedilol can be safely added to HCTZ in patients whose hypertension is inadequately controlled by HCTZ alone. Results suggest that some patients may be effectively treated with 12.5 mg carvedilol added to diuretics; upward titration of carvedilol should occur after adequate evaluation of the response to this initial dose.