[Possibilities of rational combination antihypertensive therapy: results of HEMERA international clinical trial].

Aim: To evaluate the efficiency and safety of two treatment regimens using ramipril or losartan in combination with hydrochlorothiazide (HCT) and amlodipine in grade 1-2 arterial hypertension (AH).
Subjects and Methods: The prospective, international, multicenter, randomized, open-label, controlled trial with parallel groups included 347 AH patients in Russia (n = 166), Croatia, and Ukraine. The follow-up was 12 weeks in patients not receiving antihypertensive therapy (AHT) and 13 weeks in those who had previously received AHT with regard to a washout period. The basis for two treatment regimens was ramipril or losartan. If no target blood pressure (BP) was achieved, amlodipine or HCT was added at week 4 and a third antihypertensive drug (AHD) was used 8 weeks later.
Results: At the inclusion, clinical BP was 157.64/95.5 mm Hg in 332 (61%) AH patients aged 55.9 +/- 11 years. At week 4 of monotherapy with ramipil 5 mg or losartan 50 mg, BP was reduced to 141.9/87.4 mm Hg. Addition of a second AHD further lowered BP to 131.8/81.9 mm Hg (to 127.6/79.7 at 12 weeks of treatment; p < 0.001). After 4 weeks of treatment with ramipril 5 mg or losartan 50 mg, 35% of the patients achieved target BP. At weeks 8 and 12, double or triple AHT increased the number of patients achieving the target level up to 75 and 94%, respectively. When losartan was used as monotherapy, about one third of the patients achieved target BP; 20 and 22% of the patients required the addition of a second AHD (HCT and amlodipine, respectively). Only 10% of the patients needed to take a combination of three AHDs. Nearly one third of the patients achieved target BP during monotherapy with losartan or ramipril. Double AHT involving ramipril or losartan in combination with the diuretic or amlodipine was used in 18 and 20% and in 22 and 24% of the patients, respectively. 28 and 19% of the patients received triple therapy including ramipril or losartan, amlodipine, and HCT. The most common adverse reactions were dizziness (2.4%), fatigue (1.8%), and coughing (1.2%).
Conclusion: In the patients with grades 1-2 AH, the treatment regimens using basic therapy with ramipril or losartan proved to be highly effective and allowed target BP to be achieved in 94% of cases. Both treatment regimens were comparable in view of safety; slight side effects occurred rarely (in less than 2.5% of the patients) and required that the treatment should not be discontinued.