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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Antihypertensive efficacy of lercanidipine at 2.5, 5 and 10 mg in mild to moderate essential hypertensives assessed by clinic and ambulatory blood pressure measurements. Multicenter Study Investigators.

OBJECTIVE: To evaluate the antihypertensive effect of lercanidipine once a day at three different doses (2.5, 5 and 10 mg) by clinic and ambulatory blood pressure. METHODS: After 3 weeks of a placebo run-in, 243 mild to moderate essential hypertensives (mean+/-SD age 51+/-8 years) were randomly allocated to lercanidipine at 2.5, 5 or 10 mg or a placebo for 4 weeks, in a double-blind parallel-group design. At the end of each period, supine clinic blood pressure (standard sphygmomanometry) and 24 h ambulatory blood pressure (Spacelabs 90207) were measured. The duration and homogeneity of the antihypertensive effect of the active drug compared with placebo over 24 h was evaluated by calculating the smoothness index, the ratio of the mean of the 24 hourly blood pressure changes to the corresponding SD. The higher the smoothness index, the greater and the smoother is the antihypertensive effect of a drug over the 24 h. RESULTS: In 211 patients with valid clinic blood pressure data at the end of treatment, larger systolic/diastolic blood pressure reductions were found in the 5 mg (10+/-12/8+/-6 mmHg; P< 0.05 versus placebo, diastolic blood pressure only) and the 10 mg (12+/-11/9+/-7 mmHg; P < 0.05 versus placebo, both pressures) lercanidipine groups than in the placebo (5+/-11/4+/-8 mmHg) and 2.5 mg lercanidipine (7+/-12/6 +/-7 mmHg) groups. In 105 patients with complete 24 h ambulatory blood pressure recordings, there were significantly (P< 0.05 versus placebo) larger reductions in the 10 mg (9+/-7/7+/-5 mmHg) than the 2.5 mg (1+/-10/1+/-6 mmHg) and placebo (2+/-6/1+/-4 mmHg) groups. The reduction in 24 h blood pressure with 5 mg lercanidipine (6+/-7/4+/-5 mmHg) was significantly greater compared with placebo for diastolic pressure only, and when hourly average blood pressure changes were considered, this reduction did not extend to the final hours of the dosing interval. No significant changes in the clinic or 24 h heart rate were induced by placebo or lercanidipine. The smoothness index was significantly (P< 0.05) lower for 2.5 mg lercanidipine and placebo (0.2+/-0.5 and 0.3+/-0.7 for systolic and 0.1+/-0.4 and 0.2+/-0.7 for diastolic blood pressure) than for the 5 and 10 mg doses (0.7+/-1 and 1+/-0.7 for systolic and 0.7+/-1 and 1+/-0.9 for diastolic blood pressure). CONCLUSIONS: At a dose of 10 mg, lercanidipine had a significant and durable antihypertensive effect over 24 h, but at 5 mg, the effect was less consistent and did not last 24 h. There was no clinically relevant reduction in clinic or ambulatory blood pressure with 2.5 mg lercanidipine, and the effect was superimposable on that of placebo.[1]

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