Persistence of anti-hypertensive effect after 'missed doses' of calcium antagonist with long (amlodipine) vs short (diltiazem) elimination half-life.
1. Calcium antagonists with long vs short elimination half-life may show marked differences in their antihypertensive effect during short interruptions of therapy by missed doses. 2. In the present study we evaluated the blood pressure lowering effect of amlodipine vs diltiazem both on active maintenance treatment and after active treatment was interrupted for 2 days by placebo using a double-blind randomized design. After a single blind placebo run-in period, hypertensive patients were randomized to amlodipine 5 mg once daily or diltiazem 90 mg twice daily. After 4-6 weeks, doses were increased to 10 mg once daily or 180 mg twice daily, if necessary for control of diastolic blood pressure. During week 9 or 10 on active treatment blisterpacks contained 2 days of placebo. Twenty-four hour blood pressure monitoring was performed at the end of run-in period and during week 9 and 10 on active vs interrupted therapy. 3. Active therapy by amlodipine (n = 20) lowered day systolic blood pressure by 17 +/- 2 mmHg and diastolic blood pressure by 12 +/- 2 mmHg and did not change heart rate. In second day of interrupted therapy most of these responses were still present. Diltiazem (n = 14) lowered day systolic blood pressure by 13 +/- 2 mmHg, diastolic blood pressure by 11 +/- 2 mmHg and heart rate by 10 +/- 2 beats min-1. Most of these responses had disappeared during the second day of interrupted therapy. 4. We conclude that amlodipine and diltiazem are fairly similar in lowering blood pressure from an efficacy point of view. However, during short periods of noncompliance blood pressure control will persist markedly better with the agent with a long vs the one with a short elimination half-life.
Leenen
F H
FH
Hypertension Unit, University of Ottawa Heart Institute, Ontario, Canada.
Fourney
A
A
Notman
G
G
Tanner
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017311:Amlodipine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*; D004110:Diltiazem / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D010919:Placebos; D017311:Amlodipine; D004110:Diltiazem