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 dihydropyridine calcium antagonist has additional antihypertensive effect when combined with currently used low-dose thiazide diuretic therapy. After 6 weeks with open chlorthalidone monotherapy at 25 mg daily, hypertensive patients with trough diastolic BP 90-115 mm Hg were randomly assigned to receive double-blind lacidipine, 4 mg daily or matching placebo for 4 weeks, while continuing to receive background chlorthalidone. Then patients crossed over to the alternative regimen for a second 4-week period. Clinic and 24-h ambulatory blood pressure (BP) were measured 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 lacidipine versus placebo (systolic, p < 0.01; diastolic, p < 0.05). Daytime ambulatory BP was reduced with lacidipine (p < 0.05), whereas nighttime BP was unchanged. Mean 24-h ambulatory diastolic BP also was reduced on lacidipine (p < 0.05). Heart rate was increased on lacidipine during both daytime (p < 0.01) and nighttime (p < 0.05). In conclusion, when added to chlorthalidone, lacidipine produced a significant reduction in clinic and ambulatory BP during daytime but not nighttime. This was associated with increased heart rate. Modem long-acting dihydropyridines may produce small but clinically significant additive antihypertensive effects in patients uncontrolled on low-dose thiazide monotherapy.
Stergiou
G S
GS
Hypertension Centre, Third University Department of Medicine, Sotiria Hospital, Athens, Greece.
Malakos
J S
JS
Achimastos
A D
AD
Mountokalakis
T D
TD
D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001581:Benzothiadiazines; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D002752:Chlorthalidone / Q000494:pharmacology / Q000627:therapeutic use*; D004095:Dihydropyridines / Q000494:pharmacology / Q000627:therapeutic use*; D004232:Diuretics; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011674:Pulse / Q000187:drug effects; D049993:Sodium Chloride Symporter Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001581:Benzothiadiazines; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; C060285:lacidipine; D002752:Chlorthalidone