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A multicenter study of verapamil in systemic hypertension in Thailand
A MulticenterStudyof Verapamil in SystemicHypertension in Thailand S. NONTAKANUN, N. JEAM-ANUKULKIT, P. SANSANAYUDTH,
MD, P. NGARMUKOS, MD, S. SIl-THISOOK, MD, MD, A. INTHARAKOSES, MD, P. TANPRASERT, MD, MD, A. SRIRATANABAN, MD, and Y. POLSI, MD
The antihypertensive effect and possible adverse effects of verapamil were assessed in 30 Thai patients with mild to moderate hypertension. All patients had normal blood chemistry evaluations and electrocardiograms. After a 4-week placebo period, 80 mg of verapamil was given 2 times a day for 8 weeks. Blood pressure and pulse rate were recorded both in supine and standing positions every 2 weeks. Verapamil decreased blood pressure signifi-
cantly both in supine and standing positions. The pulse rate was not significantly affected. The most common adverse effect was constipation. No vivid dreams or breathlessness were reported. The blood chemistry and electrocardiograms at the end of the study period were not significantly changed. It is concluded that verapamil reduces blood pressure in mild to moderate hypertensive Thai patients. (Am J Cardiol 1988;57:106D-107D)
s everal studies have shown that calcium antagonists can reduce blood pressure by vasodilator action.1-4 We describe a multicenter study involving several hospitals in Bangkok, Thailand. Our objectives were to observe the effectiveness of verapamil in lowering blood pressure, the response of pulse rate and the possible adverse effects in hypertensive Thai patients.
treated, either blood pressure was inadequately controlled or troublesome adverse effects occurred. Exclusion criteria were pregnancy, bradycardia (pulse rate
Methods Thirty-six patients were enrolled in this study but 6 of them dropped out for nonmedical reasons. Thirty patients (13 men and 17 women, age range 31 to 72 years, average 52) participated. All of the patients weighed between 42 and 81.3 kg, except for one who weighed 129 kg. Height varied between 1.43 and 1.73 m [average 1.59). There were 3 smokers, 16 nonsmokers and 11 were not identified either way. The subjects included in the study had essential hypertension, defined as supine diastolic blood pressure between 95 and 130 mm Hg, systolic blood pressure 1160 mm Hg or both. If they had been previously From the Section of Cardiovascular Medicine, Vachira Hospital; Chulalongkorn Hospital: Police General Hospital; Rajvithi Hospital; and Pramongkutklao Hospital, Bangkok, Thailand. Address for reprints: S. Nontakanun, Section of Cardiovascular Medicine, Vachira Hospital, Bangkok, Thailand.
Results The average blood pressure and pulse rate in the supine position are shown in Table I. The mean systolic and diastolic blood pressures and pulse rate at the first, second and third visits, when the patients received placebo, were not changed. The mean systolic blood pressure was markedly decreased from 176.5 at the third visit to 150.7 mm Hg at the fourth visit. The mean diastolic blood pressure decreased from 109.7 at the third visit to 94.3 mm Hg at the fourth visit, Both systolic and diastolic blood pressures were significantly further lowered at the fifth visit and fairly stable by the sixth and seventh visits. The mean pulse rate slowed from 80.3 beats/min at the third visit to 74.1 beats/min at the fourth visit and gradually declined further until the last visit.
February 26, 1986
TABLE I
Results of Treatment-Supine
THE AIvlERlCAN
TABLE II
Position
JOURNAL
OF CARDIOLOGY
Results of Treatmenl--Standing
Visit
Systolic BP Diastolic BP Pulse rate
2
3
4
5
6
7
177.1 111.0
171.0 107.4
176.5
150.7
142.9
109.7
94.3
89.7
136.5 87.2
137.3 87.1
74.1
70.7
68.3
66.9
78.3
80.3
107D
Position
Visit
1
77.4
Voiume 57
BP = blood pressure.
The average blood pressure and pulse rate in the standing position at each visit are shown in Table II. The changes in blood pressure and pulse rate were similar to those found in the supine position. Two adverse effects were observed; the most common was constipation. Bradycardia was the other. Eight patients complained of constipation; it was mild in 6 patients and moderate and severe in 2 other patients. Three patients had bradycardia, with a pulse rate between 50 and 60 beats/min. No vivid dreams, dizziness, orthostatic hypotension, cold extremities, breathlessness or impotence were reported. Average weight in 13 patients before and after treatment was not significantly changed. Blood chemistry, hemogram and electrocardiogram in 18 patients before and after the trial were normal. The hypotensive effect was categorized as follows: excellent-blood pressure normalized (<140/95 mm Hg); good-75% or more reduction; adequate-50 to 74% reduction; and poor-<50% reduction. Seventeen patients (57%) had excellent responses, 5 (17%) had good responses, 6 (2O%] had adequate responses and 2 (7%] had poor responses. We also asked the patients to assesstheir own overall feeling of well-being during the course of drug
Systolic BP Diastolic BP Pulse rate
I
2
3
4
5
6
7
174.1 109.7
167.1 108.6 78.8
168.5 109.2
147.2 97.0
137.1 91.6
136.0
136.5 88.1
77.2
79.2
74.8
72.3
88.1 71.0
68.2
BP = blood oressure.
administration. The responses were classified into 4 groups as follows: excellent-no complaint; goodslight complaint; fair-some complaint but feeling tolerable; and poor-feeling intolerable. Seventeen patients (57%] were excellent, 8 (27%) were good, 5 (17%] were fair and no patient could not tolerate administration of the drug. In summary, verapamil reduced blood pressure in mild to moderate essential hypertensive Thai patients. The hypotensive effect was produced gradually after the drug has been administered for 4 weeks. Pulse rate was significantly reduced in this study. Constipation and bradycardia were the most commonly reported adverse effects.
References 1. Olivari MT, Bartorelli C, P&se A, Fiorentini C, Moruzzi P, Guazzi MD. Treatment of hypertension with nifedipine. a calcium antagonist agent. Circukxtion 1979;59:1056-1062, 2. Altura BM, Altura BT, Bebrewold A. Differential effects of the calcium antagonist, verapamil, on lumen sizes of terminal arterioles and muscular venules in the cat mesenteric, pial and skeletal muscle micro vasculatures. Br f Pharmacol 198O;i’O:351-353. 3, Leon&i G, Ssla C, Bainchini C, Terzoli L, Zanchetti A. Antihypertensive and rend effects of orally administered verapamil. Ear J Clin Pharmacol 198&l&375-378. 4. Midtbok Hals 0. Verapamil in the treatment of hypertension. Curr Ther Res 1980;27:830-833.
MD, P. NGARMUKOS, MD, S. SIl-THISOOK, MD, MD, A. INTHARAKOSES, MD, P. TANPRASERT, MD, MD, A. SRIRATANABAN, MD, and Y. POLSI, MD
The antihypertensive effect and possible adverse effects of verapamil were assessed in 30 Thai patients with mild to moderate hypertension. All patients had normal blood chemistry evaluations and electrocardiograms. After a 4-week placebo period, 80 mg of verapamil was given 2 times a day for 8 weeks. Blood pressure and pulse rate were recorded both in supine and standing positions every 2 weeks. Verapamil decreased blood pressure signifi-
cantly both in supine and standing positions. The pulse rate was not significantly affected. The most common adverse effect was constipation. No vivid dreams or breathlessness were reported. The blood chemistry and electrocardiograms at the end of the study period were not significantly changed. It is concluded that verapamil reduces blood pressure in mild to moderate hypertensive Thai patients. (Am J Cardiol 1988;57:106D-107D)
s everal studies have shown that calcium antagonists can reduce blood pressure by vasodilator action.1-4 We describe a multicenter study involving several hospitals in Bangkok, Thailand. Our objectives were to observe the effectiveness of verapamil in lowering blood pressure, the response of pulse rate and the possible adverse effects in hypertensive Thai patients.
treated, either blood pressure was inadequately controlled or troublesome adverse effects occurred. Exclusion criteria were pregnancy, bradycardia (pulse rate
Methods Thirty-six patients were enrolled in this study but 6 of them dropped out for nonmedical reasons. Thirty patients (13 men and 17 women, age range 31 to 72 years, average 52) participated. All of the patients weighed between 42 and 81.3 kg, except for one who weighed 129 kg. Height varied between 1.43 and 1.73 m [average 1.59). There were 3 smokers, 16 nonsmokers and 11 were not identified either way. The subjects included in the study had essential hypertension, defined as supine diastolic blood pressure between 95 and 130 mm Hg, systolic blood pressure 1160 mm Hg or both. If they had been previously From the Section of Cardiovascular Medicine, Vachira Hospital; Chulalongkorn Hospital: Police General Hospital; Rajvithi Hospital; and Pramongkutklao Hospital, Bangkok, Thailand. Address for reprints: S. Nontakanun, Section of Cardiovascular Medicine, Vachira Hospital, Bangkok, Thailand.
Results The average blood pressure and pulse rate in the supine position are shown in Table I. The mean systolic and diastolic blood pressures and pulse rate at the first, second and third visits, when the patients received placebo, were not changed. The mean systolic blood pressure was markedly decreased from 176.5 at the third visit to 150.7 mm Hg at the fourth visit. The mean diastolic blood pressure decreased from 109.7 at the third visit to 94.3 mm Hg at the fourth visit, Both systolic and diastolic blood pressures were significantly further lowered at the fifth visit and fairly stable by the sixth and seventh visits. The mean pulse rate slowed from 80.3 beats/min at the third visit to 74.1 beats/min at the fourth visit and gradually declined further until the last visit.
February 26, 1986
TABLE I
Results of Treatment-Supine
THE AIvlERlCAN
TABLE II
Position
JOURNAL
OF CARDIOLOGY
Results of Treatmenl--Standing
Visit
Systolic BP Diastolic BP Pulse rate
2
3
4
5
6
7
177.1 111.0
171.0 107.4
176.5
150.7
142.9
109.7
94.3
89.7
136.5 87.2
137.3 87.1
74.1
70.7
68.3
66.9
78.3
80.3
107D
Position
Visit
1
77.4
Voiume 57
BP = blood pressure.
The average blood pressure and pulse rate in the standing position at each visit are shown in Table II. The changes in blood pressure and pulse rate were similar to those found in the supine position. Two adverse effects were observed; the most common was constipation. Bradycardia was the other. Eight patients complained of constipation; it was mild in 6 patients and moderate and severe in 2 other patients. Three patients had bradycardia, with a pulse rate between 50 and 60 beats/min. No vivid dreams, dizziness, orthostatic hypotension, cold extremities, breathlessness or impotence were reported. Average weight in 13 patients before and after treatment was not significantly changed. Blood chemistry, hemogram and electrocardiogram in 18 patients before and after the trial were normal. The hypotensive effect was categorized as follows: excellent-blood pressure normalized (<140/95 mm Hg); good-75% or more reduction; adequate-50 to 74% reduction; and poor-<50% reduction. Seventeen patients (57%) had excellent responses, 5 (17%) had good responses, 6 (2O%] had adequate responses and 2 (7%] had poor responses. We also asked the patients to assesstheir own overall feeling of well-being during the course of drug
Systolic BP Diastolic BP Pulse rate
I
2
3
4
5
6
7
174.1 109.7
167.1 108.6 78.8
168.5 109.2
147.2 97.0
137.1 91.6
136.0
136.5 88.1
77.2
79.2
74.8
72.3
88.1 71.0
68.2
BP = blood oressure.
administration. The responses were classified into 4 groups as follows: excellent-no complaint; goodslight complaint; fair-some complaint but feeling tolerable; and poor-feeling intolerable. Seventeen patients (57%] were excellent, 8 (27%) were good, 5 (17%] were fair and no patient could not tolerate administration of the drug. In summary, verapamil reduced blood pressure in mild to moderate essential hypertensive Thai patients. The hypotensive effect was produced gradually after the drug has been administered for 4 weeks. Pulse rate was significantly reduced in this study. Constipation and bradycardia were the most commonly reported adverse effects.
References 1. Olivari MT, Bartorelli C, P&se A, Fiorentini C, Moruzzi P, Guazzi MD. Treatment of hypertension with nifedipine. a calcium antagonist agent. Circukxtion 1979;59:1056-1062, 2. Altura BM, Altura BT, Bebrewold A. Differential effects of the calcium antagonist, verapamil, on lumen sizes of terminal arterioles and muscular venules in the cat mesenteric, pial and skeletal muscle micro vasculatures. Br f Pharmacol 198O;i’O:351-353. 3, Leon&i G, Ssla C, Bainchini C, Terzoli L, Zanchetti A. Antihypertensive and rend effects of orally administered verapamil. Ear J Clin Pharmacol 198&l&375-378. 4. Midtbok Hals 0. Verapamil in the treatment of hypertension. Curr Ther Res 1980;27:830-833.