ADDITIVE HYPOTENSIVE EFFECT OF A DIHYDROPYRIDINE CALCIUM-ANTAGONIST TO THAT PRODUCED BY A THIAZIDE DIURETIC - A DOUBLE-BLIND PLACEBO-CONTROLLED CROSSOVER TRIAL WITH AMBULATORY BLOOD-PRESSURE MONITORING

The study was designed to investigate whether a long-acting dihydropyr idine calcium antagonist has additional antihypertensive effect when c ombined with currently used low-dose thiazide diuretic therapy. After 6 weeks with open chlorthalidone monotherapy at 25 mg daily, hypertens ive patients with trough diastolic BP 90-115 mm Hg were randomly assig ned to receive double-blind lacidipine, 4 mg daily or matching placebo for 4 weeks, while continuing to receive background chlorthalidone. T hen patients crossed over to the alternative regimen for a second 4-we ek period. Clinic and 24-h ambulatory blood pressure (BP) were measure d on the final day of chlorthalidone monotherapy and on the final day of each double-blind treatment. Seventeen patients completed the study [mean age, 51.0 +/- 6.9 (SD) years]. Clinic BP was lower with lacidip ine versus placebo (systolic, p < 0.01; diastolic, p < 0.05). Daytime ambulatory BP was reduced with lacidipine (p < 0.05), whereas nighttim e BP was unchanged. Mean 24-h ambulatory diastolic BP also was reduced on lacidipine (p < 0.05). Heart rate was increased on lacidipine duri ng both daytime (p < 0.01) and nighttime (p < 0.05). In conclusion, wh en added to chlorthalidone, lacidipine produced a significant reductio n in clinic and ambulatory BP during daytime but not nighttime. This w as associated with increased heart rate. Modem long-acting dihydropyri dines may produce small but clinically significant additive antihypert ensive effects in patients uncontrolled on low-dose thiazide monothera py.