Mortality and morbidity during and after the antihypertensive and lipid-lowering treatment to prevent heart attack trial

William Cushman, Barry R. Davis, Sara L. Pressel, Jeffrey A. Cutler, Paula T. Einhorn, Charles E. Ford, Suzanne Oparil, Jeffrey L. Probstfield, Paul K. Whelton, Jackson T. Wright, Michael H. Alderman, Jan N. Basile, Henry R. Black, Richard H. Grimm, Bruce P. Hamilton, L. Julian Haywood, Stephen T. Ong, Linda B. Piller, Lara M. Simpson, Carol StanfordRobert J. Weiss

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

A randomized, double-blind, active-controlled, multicenter trial assigned 32,804 participants aged 55years and older with hypertension and ≥1 other coronary heart disease risk factors to receive chlorthalidone (n=15,002), amlodipine (n=8898), or lisinopril (n=8904) for 4 to 8years, when double-blinded therapy was discontinued. Passive surveillance continued for a total follow-up of 8 to 13years using national administrative databases to ascertain deaths and hospitalizations. During the post-trial period, fatal outcomes and nonfatal outcomes were available for 98% and 65% of participants, respectively, due to lack of access to administrative databases for the remainder. This paper assesses whether mortality and morbidity differences persisted or new differences developed during the extended follow-up. Primary outcome was cardiovascular mortality and secondary outcomes were mortality, stroke, coronary heart disease, heart failure, cardiovascular disease, and end-stage renal disease. For the post-trial period, data are not available on medications or blood pressure levels. No significant differences (P < .05) appeared in cardiovascular mortality for amlodipine (hazard ratio [HR], 1.00; 95% confidence interval [CI], 0.93-1.06) or lisinopril (HR, 0.97; CI, 0.90-1.03), each compared with chlorthalidone. The only significant differences in secondary outcomes were for heart failure, which was higher with amlodipine (HR, 1.12; CI, 1.02-1.22), and stroke mortality, which was higher with lisinopril (HR, 1.20; CI, 1.01-1.41), each compared with chlorthalidone. Similar to the previously reported in-trial result, there was a significant treatment-by-race interaction for cardiovascular disease for lisinopril vs chlorthalidone. Black participants had higher risk than non-black participants taking lisinopril compared with chlorthalidone. After accounting for multiple comparisons, none of these results were significant. These findings suggest that neither calcium channel blockers nor angiotensin-converting enzyme inhibitors are superior to diuretics for the long-term prevention of major cardiovascular complications of hypertension.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalJournal of Clinical Hypertension
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2012

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Chlorthalidone
Lisinopril
Antihypertensive Agents
Amlodipine
Myocardial Infarction
Morbidity
Lipids
Mortality
Confidence Intervals
Coronary Disease
Cardiovascular Diseases
Heart Failure
Stroke
Databases
Hypertension
Therapeutics
Fatal Outcome
Calcium Channel Blockers
Angiotensin-Converting Enzyme Inhibitors
Diuretics

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Cardiology and Cardiovascular Medicine

Cite this

Mortality and morbidity during and after the antihypertensive and lipid-lowering treatment to prevent heart attack trial. / Cushman, William; Davis, Barry R.; Pressel, Sara L.; Cutler, Jeffrey A.; Einhorn, Paula T.; Ford, Charles E.; Oparil, Suzanne; Probstfield, Jeffrey L.; Whelton, Paul K.; Wright, Jackson T.; Alderman, Michael H.; Basile, Jan N.; Black, Henry R.; Grimm, Richard H.; Hamilton, Bruce P.; Julian Haywood, L.; Ong, Stephen T.; Piller, Linda B.; Simpson, Lara M.; Stanford, Carol; Weiss, Robert J.

In: Journal of Clinical Hypertension, Vol. 14, No. 1, 01.01.2012, p. 20-31.

Research output: Contribution to journalArticle

Cushman, W, Davis, BR, Pressel, SL, Cutler, JA, Einhorn, PT, Ford, CE, Oparil, S, Probstfield, JL, Whelton, PK, Wright, JT, Alderman, MH, Basile, JN, Black, HR, Grimm, RH, Hamilton, BP, Julian Haywood, L, Ong, ST, Piller, LB, Simpson, LM, Stanford, C & Weiss, RJ 2012, 'Mortality and morbidity during and after the antihypertensive and lipid-lowering treatment to prevent heart attack trial', Journal of Clinical Hypertension, vol. 14, no. 1, pp. 20-31. https://doi.org/10.1111/j.1751-7176.2011.00568.x
Cushman, William ; Davis, Barry R. ; Pressel, Sara L. ; Cutler, Jeffrey A. ; Einhorn, Paula T. ; Ford, Charles E. ; Oparil, Suzanne ; Probstfield, Jeffrey L. ; Whelton, Paul K. ; Wright, Jackson T. ; Alderman, Michael H. ; Basile, Jan N. ; Black, Henry R. ; Grimm, Richard H. ; Hamilton, Bruce P. ; Julian Haywood, L. ; Ong, Stephen T. ; Piller, Linda B. ; Simpson, Lara M. ; Stanford, Carol ; Weiss, Robert J. / Mortality and morbidity during and after the antihypertensive and lipid-lowering treatment to prevent heart attack trial. In: Journal of Clinical Hypertension. 2012 ; Vol. 14, No. 1. pp. 20-31.
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AU - Davis, Barry R.

AU - Pressel, Sara L.

AU - Cutler, Jeffrey A.

AU - Einhorn, Paula T.

AU - Ford, Charles E.

AU - Oparil, Suzanne

AU - Probstfield, Jeffrey L.

AU - Whelton, Paul K.

AU - Wright, Jackson T.

AU - Alderman, Michael H.

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AU - Black, Henry R.

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AU - Julian Haywood, L.

AU - Ong, Stephen T.

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