title: Should Antihypertensive Treatment Recommendations Differ in Patients With and Without Coronary Heart Disease? (from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial [ALLHAT]).
abstract: Thiazide-type diuretics have been recommended for initial treatment of hypertension in most patients, but should this recommendation differ for patients with and without coronary heart disease (CHD)? The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind hypertension treatment trial in 42,418 participants with high risk of combined cardiovascular disease (CVD) (25% with preexisting CHD). This post hoc analysis compares long-term major clinical outcomes in those assigned amlodipine (n = 9048) or lisinopril (n = 9,054) with those assigned chlorthalidone (n = 15,255), stratified by CHD status. After 4 to 8 years, randomized treatment was discontinued. Total follow-up (active treatment + passive surveillance using national databases for deaths and hospitalizations) was 8 to 13 years. For most CVD outcomes, end-stage renal disease, and total mortality, there were no differences across randomized treatment arms regardless of baseline CHD status. In-trial rates of CVD were significantly higher for lisinopril compared with chlorthalidone, and rates of heart failure were significantly higher for amlodipine compared with chlorthalidone in those with and without CHD (overall hazard ratios [HRs] 1.10, p <0.001, and 1.38, p <0.001, respectively). During extended follow-up, significant outcomes according to CHD status interactions (p = 0.012) were noted in amlodipine versus chlorthalidone comparison for CVD and CHD mortality (HR 0.88, p = 0.04, and 0.84, p = 0.04, respectively) in those with CHD at baseline (HR 1.06, p = 0.15, and 1.08, p = 0.17) and in those without. The results of the overall increased stroke mortality in lisinopril compared with chlorthalidone (HR 1.2; p = 0.03) and hospitalized heart failure in amlodipine compared with chlorthalidone (HR 1.12; p = 0.01) during extended follow-up did not differ by baseline CHD status. In conclusion, these results provide no reason to alter our previous recommendation to include a properly dosed diuretic (such as chlorthalidone 12.5 to 25 mg/day) in the initial antihypertensive regimen for most hypertensive patients.
authors.affiliation: Department of Epidemiology & Population Health, Department of Medicine (General Internal Medicine), Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Alderman
authors.affiliation: The University of Texas School of Public Health, Coordinating Center for Clinical Trials, Houston, Texas.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.affiliation: The University of Texas School of Public Health, Coordinating Center for Clinical Trials, Houston, Texas. Electronic address: Linda.B.Piller@uth.tmc.edu.
authors.forename: Linda B
authors.initials: LB
authors.lastname: Piller
authors.affiliation: The University of Texas School of Public Health, Coordinating Center for Clinical Trials, Houston, Texas.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Ford
authors.affiliation: The University of Texas School of Public Health, Coordinating Center for Clinical Trials, Houston, Texas.
authors.forename: M Sarah
authors.initials: MS
authors.lastname: Baraniuk
authors.affiliation: The University of Texas School of Public Health, Coordinating Center for Clinical Trials, Houston, Texas.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pressel
authors.affiliation: State University of New York Health Sciences Center at Brooklyn, Brooklyn, New York.
authors.forename: Mahshid A
authors.initials: MA
authors.lastname: Assadi
authors.affiliation: Division of Prevention and Population Sciences, National Heart, Lung, and Blood Institute, Bethesda, Maryland.
authors.forename: Paula T
authors.initials: PT
authors.lastname: Einhorn
authors.affiliation: LAC + USC Medical Center, Keck School of Medicine, Los Angeles, California.
authors.forename: L Julian
authors.initials: LJ
authors.lastname: Haywood
authors.affiliation: Suffolk Nephrology Consultants, Stony Brook, New York.
authors.forename: Ekambaram
authors.initials: E
authors.lastname: Ilamathi
authors.affiliation: Department of Medicine and Physiology & Biophysics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.affiliation: Department of Medicine, Howard University College of Medicine, Washington, District of Columbia.
authors.forename: Tamrat M
authors.initials: TM
authors.lastname: Retta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D003324:Coronary Artery Disease / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000150:complications*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control*; D017410:Practice Guidelines as Topic / Q000592:standards*; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000959:Antihypertensive Agents; D008055:Lipids