Combination of ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension--Part 2: An open long-term study of efficacy and safety.

In an open, multicenter extension of a short-term study, 159 patients with mild to moderate hypertension were treated with either ramipril monotherapy or a combination of ramipril and hydrochlorothiazide for up to 1 year. Patients started with either 5 mg ramipril once daily (responders in the short-term study) or a combination of ramipril 5 mg plus hydrochlorothiazide 25 mg once daily. The dose could be adjusted and nonresponders to ramipril monotherapy could have hydrochlorothiazide added. In the 38 patients treated with ramipril monotherapy, the largest drop in mean blood pressure (BP) had already occurred in the previous short-term study; from Week 2 in the long-term study, the BP remained stable with means below 150/90 mmHg. In the 83 patients treated with the combination for 50 weeks or more, mean BP continued to decrease until around Week 10 in the long-term study while therapy was being adjusted. Thereafter, it also remained stable with means below 150/85 mmHg. Both treatment groups showed good mean reductions at end point, as did the group of 38 patients treated with the combination for less than 50 weeks. High response rates (84-95%) were seen in all groups at end point. The combination was well tolerated and the efficacy of ramipril in combination with hydrochlorothiazide was maintained over the 1-year period of investigation.

Combination of ramipril and hydrochlorothiazide in the treatment of mild to moderate hypertension: Part 1--A double-blind, comparative, multicenter study in nonresponders to ramipril monotherapy.

In a parallel-group multicenter study, the efficacy and safety of combination therapy with ramipril 5 mg plus hydrochlorothiazide 25 mg were compared double-blind with those of 5 mg and 10 mg ramipril monotherapy in patients with mild to moderate hypertension who had not responded adequately to ramipril 5 mg alone. Patients were initially treated single-blind for 1 week with ramipril 2.5 mg and 3 weeks with ramipril 5 mg. Of 240 patients enrolled, 165 were subsequently classed as nonresponders (diastolic blood pressure > 90 mmHg) and were randomized to one of the three double-blind treatments for a further 4 weeks. In the double-blind phase, the mean reductions in supine systolic and diastolic blood pressures at end point were significantly greater in the 5 mg plus 25 mg combination group (11.6/10.6 mmHg) than in the groups receiving ramipril 5 mg (6.2/5.9 mmHg; both p < 0.01) and ramipril 10 mg (7.4/7.1 mmHg; both p < 0.05). The proportion of responders at end point was also higher for combination therapy (72%) than for monotherapy (48% for ramipril 5 mg and 62% for ramipril 10 mg). All three treatments were well tolerated. Analysis of laboratory values revealed no clinically important changes.

Efficacy and safety of ramipril in combination with hydrochlorothiazide: results of a long-term study.

Hypertensive patients from a double-blind study comparing 5 mg of ramipril, 10 mg of ramipril, and 5 mg of ramipril + 25 mg of hydrochlorothiazide (HCTZ) were enrolled in an open 1-year extension study with ramipril and concomitant HCTZ. The starting dose of ramipril was 5 mg/day. Patients were given 25 mg of HCTZ in addition only if their diastolic blood pressure (DBP) was higher than 90 mm Hg. During treatment, the investigator was permitted to adjust the dosage of ramipril and HCTZ according to BP response and tolerance. A total of 159 patients were included in the 1-year study (86 men, 73 women, mean age of 54 years). One hundred twenty-one of the 159 patients received the combination of ramipril + HCTZ at some point in the study, 83 of them for more than 50 weeks. Thirty-eight patients were treated with ramipril alone over the entire study. In patients treated with ramipril monotherapy throughout the study, the largest drop in blood pressure occurred before visit 1. In patients treated with ramipril + HCTZ for greater than or equal to 50 weeks, the mean blood pressure continued to fall up to around week 10, while the therapy was being adjusted. Subsequently, the mean blood pressures remained low and fairly stable in both treatment groups. Similar results were seen in patients treated with the combination for less than 50 weeks. Adverse events were reported in 11 of the 38 patients in the ramipril group, in 22 of 83 patients treated with the combination for more than 50 weeks, and in 9 of 38 patients treated with the combination for 50 weeks or less. The analysis of the laboratory values revealed no general deterioration. It can be concluded that ramipril alone and in combination with HCTZ is an effective and safe drug for the long-term treatment of essential hypertension.