Principal Results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial

Henry R. Black, William J. Elliott, Gregory Grandits, Patricia Grambsch, Tracy Lucente, William B. White, James D. Neaton, Richard H. Grimm, Lennart Hansson, Yves Lacourcière, James Muller, Peter Sleight, Michael A. Weber, Gordon Williams, Janet Wittes, Alberto Zanchetti, Robert J. Anders

Research output: Contribution to journalArticle

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Abstract

Context: Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. Objective: To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. Intervention: Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, β-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. Main Outcome Measures: First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. Results: Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P=.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Non-stroke hemorrhage was more common with participants in the COER-verapamil group (n= 118) compared with the atenolol or hydrochlorothiazide group (n=79) (HR, 1.54 [95% CI, 1.16-2.04]; P=.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). Conclusions: The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or β-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or β-blocker treatment.

Original languageEnglish
Pages (from-to)2073-2082
Number of pages10
JournalJournal of the American Medical Association
Volume289
Issue number16
DOIs
Publication statusPublished - Apr 23 2003

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Verapamil
Hydrochlorothiazide
Atenolol
Cardiovascular Diseases
Confidence Intervals
Diuretics
Stroke
Myocardial Infarction
Blood Pressure
Calcium
Calcium Channels
Cardiomyopathies
Angiotensin-Converting Enzyme Inhibitors
Pharmaceutical Preparations
Antihypertensive Agents
Randomized Controlled Trials
Outcome Assessment (Health Care)
Hemorrhage
Hypertension
Physicians

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Black, H. R., Elliott, W. J., Grandits, G., Grambsch, P., Lucente, T., White, W. B., ... Anders, R. J. (2003). Principal Results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial. Journal of the American Medical Association, 289(16), 2073-2082. https://doi.org/10.1001/jama.289.16.2073

Principal Results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial. / Black, Henry R.; Elliott, William J.; Grandits, Gregory; Grambsch, Patricia; Lucente, Tracy; White, William B.; Neaton, James D.; Grimm, Richard H.; Hansson, Lennart; Lacourcière, Yves; Muller, James; Sleight, Peter; Weber, Michael A.; Williams, Gordon; Wittes, Janet; Zanchetti, Alberto; Anders, Robert J.

In: Journal of the American Medical Association, Vol. 289, No. 16, 23.04.2003, p. 2073-2082.

Research output: Contribution to journalArticle

Black, HR, Elliott, WJ, Grandits, G, Grambsch, P, Lucente, T, White, WB, Neaton, JD, Grimm, RH, Hansson, L, Lacourcière, Y, Muller, J, Sleight, P, Weber, MA, Williams, G, Wittes, J, Zanchetti, A & Anders, RJ 2003, 'Principal Results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial', Journal of the American Medical Association, vol. 289, no. 16, pp. 2073-2082. https://doi.org/10.1001/jama.289.16.2073
Black, Henry R. ; Elliott, William J. ; Grandits, Gregory ; Grambsch, Patricia ; Lucente, Tracy ; White, William B. ; Neaton, James D. ; Grimm, Richard H. ; Hansson, Lennart ; Lacourcière, Yves ; Muller, James ; Sleight, Peter ; Weber, Michael A. ; Williams, Gordon ; Wittes, Janet ; Zanchetti, Alberto ; Anders, Robert J. / Principal Results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial. In: Journal of the American Medical Association. 2003 ; Vol. 289, No. 16. pp. 2073-2082.
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abstract = "Context: Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. Objective: To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. Intervention: Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, β-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. Main Outcome Measures: First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. Results: Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95{\%} confidence interval [CI], 0.88-1.18; P=.77). For fatal or nonfatal stroke, the HR was 1.15 (95{\%} CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95{\%} CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95{\%} CI, 0.87-1.37). The HR was 1.05 (95{\%} CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95{\%} CI, 0.93-1.26) for all-cause mortality. Non-stroke hemorrhage was more common with participants in the COER-verapamil group (n= 118) compared with the atenolol or hydrochlorothiazide group (n=79) (HR, 1.54 [95{\%} CI, 1.16-2.04]; P=.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95{\%} CI, 0.86-1.53). Conclusions: The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or β-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or β-blocker treatment.",
author = "Black, {Henry R.} and Elliott, {William J.} and Gregory Grandits and Patricia Grambsch and Tracy Lucente and White, {William B.} and Neaton, {James D.} and Grimm, {Richard H.} and Lennart Hansson and Yves Lacourci{\`e}re and James Muller and Peter Sleight and Weber, {Michael A.} and Gordon Williams and Janet Wittes and Alberto Zanchetti and Anders, {Robert J.}",
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TY - JOUR

T1 - Principal Results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial

AU - Black, Henry R.

AU - Elliott, William J.

AU - Grandits, Gregory

AU - Grambsch, Patricia

AU - Lucente, Tracy

AU - White, William B.

AU - Neaton, James D.

AU - Grimm, Richard H.

AU - Hansson, Lennart

AU - Lacourcière, Yves

AU - Muller, James

AU - Sleight, Peter

AU - Weber, Michael A.

AU - Williams, Gordon

AU - Wittes, Janet

AU - Zanchetti, Alberto

AU - Anders, Robert J.

PY - 2003/4/23

Y1 - 2003/4/23

N2 - Context: Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. Objective: To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. Intervention: Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, β-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. Main Outcome Measures: First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. Results: Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P=.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Non-stroke hemorrhage was more common with participants in the COER-verapamil group (n= 118) compared with the atenolol or hydrochlorothiazide group (n=79) (HR, 1.54 [95% CI, 1.16-2.04]; P=.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). Conclusions: The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or β-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or β-blocker treatment.

AB - Context: Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. Objective: To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. Intervention: Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, β-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. Main Outcome Measures: First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. Results: Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P=.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Non-stroke hemorrhage was more common with participants in the COER-verapamil group (n= 118) compared with the atenolol or hydrochlorothiazide group (n=79) (HR, 1.54 [95% CI, 1.16-2.04]; P=.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). Conclusions: The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or β-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or β-blocker treatment.

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