Clinical results of the verapamil in hypertension and atherosclerosis study

Enrico Agabiti Rosei, Cesare Dal Palù, Gastone Leonetti, Bruno Magnani, Achille Pessina, Alberto Zanchetti

Research output: Contribution to journalArticle

Abstract

Objective. The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients. Design. After a 3-week placebo run-in period, 1,414 hypertensive patients [692 men and 722 women, aged 53.2 ± 7 years, blood pressure 168.9 ± 10.5/102.2 ± 5.0 mmHg (means ± SD)] were assigned randomly to be administered either 240 mg sustained-release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25-50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study. Results. After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthalidone, both by analysis of variance, P <0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 26.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to ≤ 90 mmHg or to ≤ 95 mmHg with a ≤ 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group. A decrease in heart rate (by 5.8%) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P <0.01) and in the total cholesterol: high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P <0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9%) and hypokalemia (serum K <3.5 mmol/l; 24.6 versus 4.4%) were observed for the chlorthalidone group (P <0.01, versus verapamil for both). Adverse events were reported by 32.5% of patients treated with verapamil and by 33.4% of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7%) and asthenia in members of the chlorthalidone group (8.5%). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS). Conclusion. Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.

Original languageEnglish
Pages (from-to)1337-1344
Number of pages8
JournalJournal of Hypertension
Volume15
Issue number11
DOIs
Publication statusPublished - 1997

Fingerprint

Chlorthalidone
Verapamil
Atherosclerosis
Hypertension
Blood Pressure
Hypokalemia
Therapeutics
Safety
Asthenia
Hyperuricemia
Captopril
Constipation
Antihypertensive Agents
Analysis of Variance
Electrocardiography
Heart Rate
Placebos

Keywords

  • Blood pressure
  • Cardiovascular events
  • Chlorthalidone
  • Hyperuricemia
  • Hypokalemia
  • Verapamil

ASJC Scopus subject areas

  • Endocrinology
  • Internal Medicine

Cite this

Rosei, E. A., Dal Palù, C., Leonetti, G., Magnani, B., Pessina, A., & Zanchetti, A. (1997). Clinical results of the verapamil in hypertension and atherosclerosis study. Journal of Hypertension, 15(11), 1337-1344. https://doi.org/10.1097/00004872-199715110-00019

Clinical results of the verapamil in hypertension and atherosclerosis study. / Rosei, Enrico Agabiti; Dal Palù, Cesare; Leonetti, Gastone; Magnani, Bruno; Pessina, Achille; Zanchetti, Alberto.

In: Journal of Hypertension, Vol. 15, No. 11, 1997, p. 1337-1344.

Research output: Contribution to journalArticle

Rosei, EA, Dal Palù, C, Leonetti, G, Magnani, B, Pessina, A & Zanchetti, A 1997, 'Clinical results of the verapamil in hypertension and atherosclerosis study', Journal of Hypertension, vol. 15, no. 11, pp. 1337-1344. https://doi.org/10.1097/00004872-199715110-00019
Rosei, Enrico Agabiti ; Dal Palù, Cesare ; Leonetti, Gastone ; Magnani, Bruno ; Pessina, Achille ; Zanchetti, Alberto. / Clinical results of the verapamil in hypertension and atherosclerosis study. In: Journal of Hypertension. 1997 ; Vol. 15, No. 11. pp. 1337-1344.
@article{6e0597e4821944dfa079cae81285c64f,
title = "Clinical results of the verapamil in hypertension and atherosclerosis study",
abstract = "Objective. The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients. Design. After a 3-week placebo run-in period, 1,414 hypertensive patients [692 men and 722 women, aged 53.2 ± 7 years, blood pressure 168.9 ± 10.5/102.2 ± 5.0 mmHg (means ± SD)] were assigned randomly to be administered either 240 mg sustained-release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25-50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study. Results. After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6{\%} with verapamil and by 16.9/16.2{\%} with chlorthalidone, both by analysis of variance, P <0.0001). The patients for whom we added captopril treatment constituted 22.6{\%} of the verapamil and 26.2{\%} of the chlorthalidone group; while 11.6 and 12.2{\%} of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to ≤ 90 mmHg or to ≤ 95 mmHg with a ≤ 10{\%} decrease) was achieved for 69.3{\%} of the verapamil and 66.9{\%} of the chlorthalidone group. A decrease in heart rate (by 5.8{\%}) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P <0.01) and in the total cholesterol: high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P <0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9{\%}) and hypokalemia (serum K <3.5 mmol/l; 24.6 versus 4.4{\%}) were observed for the chlorthalidone group (P <0.01, versus verapamil for both). Adverse events were reported by 32.5{\%} of patients treated with verapamil and by 33.4{\%} of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7{\%}) and asthenia in members of the chlorthalidone group (8.5{\%}). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS). Conclusion. Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.",
keywords = "Blood pressure, Cardiovascular events, Chlorthalidone, Hyperuricemia, Hypokalemia, Verapamil",
author = "Rosei, {Enrico Agabiti} and {Dal Pal{\`u}}, Cesare and Gastone Leonetti and Bruno Magnani and Achille Pessina and Alberto Zanchetti",
year = "1997",
doi = "10.1097/00004872-199715110-00019",
language = "English",
volume = "15",
pages = "1337--1344",
journal = "Journal of Hypertension",
issn = "0263-6352",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Clinical results of the verapamil in hypertension and atherosclerosis study

AU - Rosei, Enrico Agabiti

AU - Dal Palù, Cesare

AU - Leonetti, Gastone

AU - Magnani, Bruno

AU - Pessina, Achille

AU - Zanchetti, Alberto

PY - 1997

Y1 - 1997

N2 - Objective. The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients. Design. After a 3-week placebo run-in period, 1,414 hypertensive patients [692 men and 722 women, aged 53.2 ± 7 years, blood pressure 168.9 ± 10.5/102.2 ± 5.0 mmHg (means ± SD)] were assigned randomly to be administered either 240 mg sustained-release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25-50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study. Results. After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthalidone, both by analysis of variance, P <0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 26.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to ≤ 90 mmHg or to ≤ 95 mmHg with a ≤ 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group. A decrease in heart rate (by 5.8%) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P <0.01) and in the total cholesterol: high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P <0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9%) and hypokalemia (serum K <3.5 mmol/l; 24.6 versus 4.4%) were observed for the chlorthalidone group (P <0.01, versus verapamil for both). Adverse events were reported by 32.5% of patients treated with verapamil and by 33.4% of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7%) and asthenia in members of the chlorthalidone group (8.5%). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS). Conclusion. Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.

AB - Objective. The Verapamil in Hypertension and Atherosclerosis Study (VHAS) is a prospective randomized study the objective of which was to compare the long-term effects of verapamil and chlorthalidone on the blood pressure, clinical safety, and the progression/regression of carotid wall lesions in members of a large population of hypertensive patients. Design. After a 3-week placebo run-in period, 1,414 hypertensive patients [692 men and 722 women, aged 53.2 ± 7 years, blood pressure 168.9 ± 10.5/102.2 ± 5.0 mmHg (means ± SD)] were assigned randomly to be administered either 240 mg sustained-release verapamil (n = 707) or 25 mg chlorthalidone (n = 707) once a day for 2 years. The study design was double blind for the first 6 months and open thereafter. 25-50 mg/day captopril were added to the treatment of non-responding patients; subsequently, patients not responding to combined therapy were switched to any therapy chosen by the treating doctors (free therapy). The blood pressure of the sitting subject, heart rate, and a standard clinical safety profile (electrocardiogram, laboratory tests, adverse events, cardiovascular events, and deaths) were assessed regularly throughout the study. Results. After 2 years the systolic and diastolic blood pressures were reduced significantly in members of both treatment groups (by 16.3/16.6% with verapamil and by 16.9/16.2% with chlorthalidone, both by analysis of variance, P <0.0001). The patients for whom we added captopril treatment constituted 22.6% of the verapamil and 26.2% of the chlorthalidone group; while 11.6 and 12.2% of patients in these groups, respectively, were administered free therapy. Normalization of the diastolic blood pressure (to ≤ 90 mmHg or to ≤ 95 mmHg with a ≤ 10% decrease) was achieved for 69.3% of the verapamil and 66.9% of the chlorthalidone group. A decrease in heart rate (by 5.8%) occurred in members of the verapamil group only. A decrease in total serum cholesterol (from 223.6 to 216.9 mg/dl, P <0.01) and in the total cholesterol: high-density lipoprotein cholesterol ratio (from 4.9 to 4.5, P <0.01) was noted for the verapamil group only, whereas significantly greater rates of hyperuricemia (plasma urate > 7.0 mg/dl; 10.8 versus 3.9%) and hypokalemia (serum K <3.5 mmol/l; 24.6 versus 4.4%) were observed for the chlorthalidone group (P <0.01, versus verapamil for both). Adverse events were reported by 32.5% of patients treated with verapamil and by 33.4% of those treated with chlorthalidone. The most frequent adverse events were constipation in members of the verapamil group (13.7%) and asthenia in members of the chlorthalidone group (8.5%). In total 315 dropped out (153 from the verapamil and 162 from the chlorthalidone group). The occurrence of cardiovascular events was similar for both treatments (42 events for verapamil and 43 for chlorthalidone, NS). Conclusion. Similar antihypertensive efficacies, tolerabilities and cardiovascular event rates were observed with verapamil and with chlorthalidone. However, treatment with chlorthalidone was associated with significantly higher incidences of hyperuricemia and hypokalemia than was treatment with verapamil.

KW - Blood pressure

KW - Cardiovascular events

KW - Chlorthalidone

KW - Hyperuricemia

KW - Hypokalemia

KW - Verapamil

UR - http://www.scopus.com/inward/record.url?scp=0031278797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031278797&partnerID=8YFLogxK

U2 - 10.1097/00004872-199715110-00019

DO - 10.1097/00004872-199715110-00019

M3 - Article

C2 - 9383184

AN - SCOPUS:0031278797

VL - 15

SP - 1337

EP - 1344

JO - Journal of Hypertension

JF - Journal of Hypertension

SN - 0263-6352

IS - 11

ER -