Ambulatory 24-h blood pressure assessment of the felodipine-metoprolol combination versus amlodipine in mild to moderate hypertension. Lorraine General Physician Investigators Group.
OBJECTIVE
To measure the time effect profiles of a once daily administered combination tablet felodipine-metoprolol 5/50 mg (Logimax, Astra) and amlodipine 5 mg (Norvasc, Pfizer) on blood pressure and heart rate using 24-h ambulatory blood pressure monitoring.


METHODS
Randomized multicentre parallel-group study with a single-blind placebo run-in period of 4 weeks duration and a 6-week double-blind active treatment period.


METHODS
Out of 245 randomized outpatients (90 men, 155 women) with uncomplicated mild-to-moderate primary hypertension and mean sitting diastolic blood pressure (DBP) 95-115 mmHg inclusive, 212 (102 on felodipine-metoprolol, 110 on amlodipine) were eligible for analysis. 24-h ambulatory blood pressure monitoring was performed at the end of the placebo run-in (baseline) and after 6 weeks active treatment (posttreatment).


RESULTS
Both felodipine-metoprolol and amlodipine induced smooth and consistent reduction in DBP and systolic blood pressure throughout the 24-h period, hence not altering the diurnal rhythm. However, felodipine-metoprolol reduced all average blood pressures (24-h, day- and night-time) more than amlodipine (for 24-h average blood pressure 14.4/9.5 mmHg and 8.9/5.5 mmHg, respectively). Medians of individual diastolic trough-to-peak (T/P) ratios were similar for felodipine-metoprolol and amlodipine (54 and 50%, respectively), while for the systolic T/P ratios, the corresponding values were 74 and 35%, repectively; no significant difference between treatments was seen. As distinguished from amlodipine, both heart rate and rate pressure product were markedly decreased on felodipine-metoprolol throughout the 24-h period and even during the early morning hours. In general, both treatments were well tolerated.


CONCLUSIONS
Both felodipine-metoprolol and amlodipine achieved optimal control of blood pressure during the inter-dosing interval in line with their pharmokinetic profiles. The vasodilatory adverse events were slightly more reported with felodipine-metoprolol combination, but due to more pronounced lowering of the average blood pressures and the potent additional effect on heart rate and rate pressure product, the efficacy/tolerability balance seems to be equal to or better than that obtained with monotherapy such as amlodipine.
Centre d'investigation clinique, INSERM-CHU, Nancy, France. cic@chu-nancy.fr
F
F
Zannad
J M
JM
Boivin
D017311:Amlodipine / Q000008:administration & dosage*; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D004359:Drug Therapy, Combination; D015736:Felodipine / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008790:Metoprolol / Q000008:administration & dosage*; D008875:Middle Aged
D000959:Antihypertensive Agents; D017311:Amlodipine; D008790:Metoprolol; D015736:Felodipine