Relationship between doses of 1, 2, 4, and 6 mg lacidipine and blood pressure response in a randomised, double blind, parallel-group, placebo-controlled, comparative study

Objective To investigate the dose-response relationship of lacidipine, admi nistered once daily for 4 weeks to patients with moderate essential hyperte nsion and to define the lowest dose significantly affecting diastolic blood pressure in comparison with placebo. The trough to peak ratio was also inv estigated. Secondary aims were the assessment of safety profile, including the orthostatic reaction measured according to Schellong and Luberitz [18]. Methods Two-hundred and fifty-nine patients, recruited in thirteen German c entres, were randomly allocated in a balanced manner to either placebo or a ctive lacidipine, at escalating doses of 1, 2, 4 and 6 mg, after a placebo run-in period of 4 weeks. Results After treatment for 1 month, a dose-response relationship was found in blood-pressure-lowering effects and in normalisation rates. The dose re gimen of 2 mg was found to be the lowest active dose to have an antihyperte nsive activity significantly superior to placebo, in terms of mean alterati on in values of diastolic blood pressure (-12.7 mmHg versus -8.6 mmHg, P< 0 .05). All lacidipine doses were shown to have a favourable trough-to-peak r atio, by establishing well-controlled blood pressure over a 24-h period. To lerability was also very good, with a reported rate of adverse events in th e 2 and 4 mg groups similar to that shown by the placebo group. In addition , no effect was noted in any treatment group on the hypotensive reaction fo llowing an orthostatic test performed after 15 days of treatment. Conclusions Lacidipine at a dose of 2 mg once daily could represent the rec ommended starting dose in the treatment of moderate hypertensive patients, and a dose of 4 mg is the optimum one that should be used as standard, sinc e it provides the optimal balance between safety and efficacy. I Hypertens 16 (suppl 9):S45-S50 (C) 1998 Lippincott Williams & Wilkins.