Acta med. scand. Vol. 199, pp. 71-74, 1976
Comparison between Metoprolol and Propranolol as Antihypertensive Agents A Double-blind Cross-over Study
C. Bengtsson From Department
of' Medicine
II, Sulzl~ren'sHospital, University of Ciiteborg, Giitehorg, Sweden
ABSTRACT. A new selective P-adrenergic blocking agent-metoproloLis compared to a non-selective P-adrenergic blocking agent-propranolohccording to a double-blind cross-over technique in 23 hypertensive women, who had previously taken alprenolol and propranolol during different periods. No significant differences were found for blood pressure, heart rate, body weight or serum uric acid. No side-effects which could be related to the therapy were seen with either drug. Metoprolol is a new selective adrenergic PI-receptor blocking agent (3, 10) which has been shown to reduce the blood pressure (BP) significantly compared to placebo and also to maintain the BP a t a low value during a long-term follow-up (7). As part of the research programme for this substance, metoprolol has been compared to propranolol in a double-blind cross-over study. The substances were given in doses which had been shown t o reduce exercise tachycardia to the same extent ( 1 I).
MATERIAL The subjects were recruited from a material of 26 women who had previously participated in a trial comparing alprenolol and propranolol (6). Twenty-four women, aged 50-64 years (mean 56) when admitted, were included in the study and 23 completed it. One woman was excluded due to disease not related to her hypertension or antihypertensive treatment. Except for one woman who had experienced breathlessness on moderate exertion, none had a history or signs of cardiac or renal insufficiency. They were all classified as grade 1-2 according to WHOs classification of hypertension. None had severe eye ground changes. One woman was classified as FH 0 according to Keith-Wagener-Barker, the others as FH 1-11,
METHODS Fig. I shows the design of the study. After a run-in period of eight weeks, during which the participants received placebo. they were randomly allocated to metoprolol or propranolol as first active drug. The drugs were given double-blind and cross-over. Each period lasted for eight weeks, the total time for the study, including the run-in placebo period, being 24 weeks. All participants started and completed the trial at about the same time. The subjects underwent physical examination before and after the run-in period and at the end of the placebo and treatment periods. BP was measured after about 10 min rest with the patient in the seated, supine and standing positions by the same examiner using a mercury sphygmomanometer as described previously (5). Heart rate (HR) was measured with the patient in the seated position. Bilirubin, SGOT, SGPT, alkaline phosphatases and serum uric acid were determined at the Central Laboratory of this hospital. Serum uric acid was recorded according to an enzymatic method. Fifty rng of metoprolol tartrate was considered equipotent to 40 mg of propranolol hydrochloride ( 1 1 ) . According to previous individual titration, the patients received 50 mg or 100 mg of metoprolol t.i.d. and 40 mg or 80 mg of propranolol t.i.d. during the treatment periods. The same number of tablets was also prescribed during the run-in period. Of those who completed the study, eight received the higher dose and 15 the lower. Twelve women were given metoprolol as the first active drug and I I started with propranolol. The placebo tablets and the tablets containing active drug were of the same appearance and taste as the metoprolol tablets which they had taken previously. The metoprolol and propranolol tablets had the same dissolution rate in vitro. No special information was given when the placebo period was started. During the treatment periods the women were informed that they were to receive two similar drugs in order to find out which one was the best for them. Statistical merhods. Data from the clinical controls were collected according to a special schedule. There were no missing data. The significance of difference between Acta med. scand. 199
72
C. Bengtsson
Gioup I
(n-12) Group II (n=ll)
'
PLACEBO
5
PLACEBO
.
METOPROLOL
.
PROPRANOLOL
8
,
PROPRANOLOL
.
METOPROLOL
16
mmHg
-
160 24
weeks
1
t
i
i
Fig. 1 . Design of the study. Arrows denote clinical examinations.
140-
120-
100-
sample means was estimated by Student's t-test for the means of differences between paired observations. I n this way each subject acted as her own control throughout the study. The differences were considered statistically significant forp
Comparison between Metoprolol and Propranolol as Antihypertensive Agents A Double-blind Cross-over Study
C. Bengtsson From Department
of' Medicine
II, Sulzl~ren'sHospital, University of Ciiteborg, Giitehorg, Sweden
ABSTRACT. A new selective P-adrenergic blocking agent-metoproloLis compared to a non-selective P-adrenergic blocking agent-propranolohccording to a double-blind cross-over technique in 23 hypertensive women, who had previously taken alprenolol and propranolol during different periods. No significant differences were found for blood pressure, heart rate, body weight or serum uric acid. No side-effects which could be related to the therapy were seen with either drug. Metoprolol is a new selective adrenergic PI-receptor blocking agent (3, 10) which has been shown to reduce the blood pressure (BP) significantly compared to placebo and also to maintain the BP a t a low value during a long-term follow-up (7). As part of the research programme for this substance, metoprolol has been compared to propranolol in a double-blind cross-over study. The substances were given in doses which had been shown t o reduce exercise tachycardia to the same extent ( 1 I).
MATERIAL The subjects were recruited from a material of 26 women who had previously participated in a trial comparing alprenolol and propranolol (6). Twenty-four women, aged 50-64 years (mean 56) when admitted, were included in the study and 23 completed it. One woman was excluded due to disease not related to her hypertension or antihypertensive treatment. Except for one woman who had experienced breathlessness on moderate exertion, none had a history or signs of cardiac or renal insufficiency. They were all classified as grade 1-2 according to WHOs classification of hypertension. None had severe eye ground changes. One woman was classified as FH 0 according to Keith-Wagener-Barker, the others as FH 1-11,
METHODS Fig. I shows the design of the study. After a run-in period of eight weeks, during which the participants received placebo. they were randomly allocated to metoprolol or propranolol as first active drug. The drugs were given double-blind and cross-over. Each period lasted for eight weeks, the total time for the study, including the run-in placebo period, being 24 weeks. All participants started and completed the trial at about the same time. The subjects underwent physical examination before and after the run-in period and at the end of the placebo and treatment periods. BP was measured after about 10 min rest with the patient in the seated, supine and standing positions by the same examiner using a mercury sphygmomanometer as described previously (5). Heart rate (HR) was measured with the patient in the seated position. Bilirubin, SGOT, SGPT, alkaline phosphatases and serum uric acid were determined at the Central Laboratory of this hospital. Serum uric acid was recorded according to an enzymatic method. Fifty rng of metoprolol tartrate was considered equipotent to 40 mg of propranolol hydrochloride ( 1 1 ) . According to previous individual titration, the patients received 50 mg or 100 mg of metoprolol t.i.d. and 40 mg or 80 mg of propranolol t.i.d. during the treatment periods. The same number of tablets was also prescribed during the run-in period. Of those who completed the study, eight received the higher dose and 15 the lower. Twelve women were given metoprolol as the first active drug and I I started with propranolol. The placebo tablets and the tablets containing active drug were of the same appearance and taste as the metoprolol tablets which they had taken previously. The metoprolol and propranolol tablets had the same dissolution rate in vitro. No special information was given when the placebo period was started. During the treatment periods the women were informed that they were to receive two similar drugs in order to find out which one was the best for them. Statistical merhods. Data from the clinical controls were collected according to a special schedule. There were no missing data. The significance of difference between Acta med. scand. 199
72
C. Bengtsson
Gioup I
(n-12) Group II (n=ll)
'
PLACEBO
5
PLACEBO
.
METOPROLOL
.
PROPRANOLOL
8
,
PROPRANOLOL
.
METOPROLOL
16
mmHg
-
160 24
weeks
1
t
i
i
Fig. 1 . Design of the study. Arrows denote clinical examinations.
140-
120-
100-
sample means was estimated by Student's t-test for the means of differences between paired observations. I n this way each subject acted as her own control throughout the study. The differences were considered statistically significant forp
