How much effect of different antihypertensive medications on cardiovascular outcomes is attributable to their effects on blood pressure?

Abstract

The debate over whether certain antihypertensive medications have benefits beyond what would be expected from their blood pressure lowering spurred the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, which randomized 42,418 participants to chlorthalidone (15,255), amlodipine (9048), lisinopril (9054), or doxazosin (9061). We compared chlorthalidone, the active control, with each of the other three agents with respect to the primary outcome, fatal coronary heart disease or nonfatal myocardial infarction, and several other clinical endpoints. The arms were similar with respect to the primary endpoint, although some differences were found for other endpoints, most notably heart failure. Although the desire was to achieve similar blood pressure reductions in the four arms, we found some systolic blood pressure and diastolic blood pressure differences. A natural question is to what degree can observed treatment group differences in cardiovascular outcomes be attributed to these blood pressure differences. The purpose of this paper was to delineate the problems inherent in attempting to answer this question, and to present analyses intended to overcome these problems.

• Authors: Michael Proschan, Charles E Ford, Jeffrey A Cutler, James F Graumlich, Valory Pavlik, William C Cushman, Barry R Davis, Michael H Alderman, David Gordon, Curt D Furberg, Stanley S Franklin, Samuel S Blumenthal, Richard S Castaldo, Richard A Preston, LHAT Collaborative Research Group
• Journal: Statistics in medicine (Stat Med) Vol. 32 Issue 5 Pg. 884-97 (Feb 28 2013) ISSN: 1097-0258 [Electronic] England
• PMID: 22961832 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 John Wiley & Sons, Ltd.

Chemical References

• Antihypertensive Agents
• Amlodipine
• Lisinopril
• Chlorthalidone

Topics

• Amlodipine (therapeutic use)
• Antihypertensive Agents (therapeutic use)
• Biostatistics (methods)
• Blood Pressure (drug effects)
• Cardiovascular Diseases (prevention & control)
• Chlorthalidone (therapeutic use)
• Coronary Disease (prevention & control)
• Endpoint Determination (statistics & numerical data)
• Heart Failure (prevention & control)
• Humans
• Hypertension (drug therapy, physiopathology)
• Lisinopril (therapeutic use)
• Myocardial Infarction (prevention & control)
• Randomized Controlled Trials as Topic (statistics & numerical data)
• Regression Analysis
• Treatment Outcome