Different Concepts in First-Line Treatment of Essential Hypertension

Low-dose combination therapy has been proposed as a rational first-line approach to hypertension treatment. We compared the efficacy and tolerability of the fixed combination of reserpine (0.1 mg) plus the thiazide clopamid (5 mg) with its single components and the calcium-antagonist nitrendipine (20 mg) in a randomized, double-blind, parallel study of 273 hypertensive patients with diastolic blood pressure (BP) between 100 and 114 mm Hg. The four groups did not differ regarding baseline characteristics (mean age, 58 years; 51% men; mean BP after a 2-week placebo period, 158 to 160/103 to 104 mm Hg). After 6 weeks of treatment with one capsule daily, mean reductions in sitting BP from baseline at 24 hours after dosing in the reserpine-clopamid combination, reserpine, clopamid, and nitrendipine groups were −23.0/−17.1, −14.0/−11.7, −13.6/−11.9, and −11.6/−12.3 mm Hg, respectively (2 P <.01). The corresponding normalization rates (diastolic BP <90 mm Hg) were 55%, 40%, 36%, and 33% (2 P =.11). All patients whose BP had not been normalized at this point received two capsules of the respective medication once daily from weeks 7 to 12. At week 12, mean BP reductions were −25.7/−18.1, −14.6/−12.2, −17.7/−13.4, and −14.9/−15.3 mm Hg in the four groups, respectively (2 P <.01). The respective normalization rates were 69%, 35%, 39%, and 45% (2 P <.0001). Linear regression modeling indicated that reserpine and clopamid combined acted more than additively. As regards tolerability, adverse experiences were observed in 27%, 28%, 29%, and 48% of patients, respectively (2 P <.05). The respective rates of premature discontinuation because of adverse effects were 3%, 3%, 7%, and 13% (2 P =.06). In conclusion, a low-dose combination of reserpine and clopamid lowered BP significantly more than both the components alone and nitrendipine. Moreover, the combination was tolerated as well as its components and significantly better than nitrendipine. Thus, the use of this low-dose reserpine-thiazide combination appears to be a rational alternative to conventional monotherapy in the first-line treatment of hypertension.