title: Stroke outcomes among participants randomized to chlorthalidone, amlodipine or lisinopril in ALLHAT.
abstract: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, practice-based, active-control, comparative effectiveness trial in 33,357 high-risk hypertensive participants. ALLHAT compared cardiovascular disease outcomes in participants initially treated with an angiotensin-converting enzyme inhibitor (lisinopril), a calcium channel blocker (amlodipine), or a thiazide-type diuretic (chlorthalidone). We report stroke outcomes in 1517 participants in-trial and 1596 additional participants during post-trial passive surveillance, for a total follow-up of 8-13 years. Stroke rates were higher with lisinopril (6-year rate/100 = 6.4) than with chlorthalidone (5.8) or amlodipine (5.5) in-trial but not including post-trial (10-year rates/100 = 13.2 [chlorthalidone], 13.1[amlodipine], and 13.7 [lisinopril]). In-trial differences were driven by race (race-by-lisinopril/chlorthalidone interaction P = .005, race-by-amlodipine/lisinopril interaction P = .012) and gender (gender-by-lisinopril/amlodipine interaction P = .041), separately. No treatment differences overall, or by race or gender, were detected over the 10-year period. No differences appeared among treatment groups in adjusted risk of all-cause mortality including post-trial for participants with nonfatal in-trial strokes. Among Blacks and women, lisinopril was less effective in preventing stroke in-trial than either chlorthalidone or amlodipine, even after adjusting for differences in systolic blood pressure. These differences abated by the end of the post-trial period.
authors.affiliation: Coordinating Center for Clinical Trials, Division of Biostatistics, University of Texas School of Public Health, Houston, TX, USA. Electronic address: Jose-Miguel.Yamal@uth.tmc.edu.
authors.forename: José-Miguel
authors.initials: JM
authors.lastname: Yamal
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.affiliation: Coordinating Center for Clinical Trials, Division of Biostatistics, University of Texas School of Public Health, Houston, TX, USA.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Davis
authors.affiliation: Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Alderman
authors.affiliation: Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Calhoun
authors.affiliation: Preventive Medicine Section, Memphis Veterans Affairs Medical Center, Memphis, TN, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Cushman
authors.affiliation: Jefferson Regional Medical Center, Jefferson Hills, PA, USA.
authors.forename: Herbert F
authors.initials: HF
authors.lastname: Fendley
authors.affiliation: Department of Medicine, University of California, Irvine, CA, USA.
authors.forename: Stanley S
authors.initials: SS
authors.lastname: Franklin
authors.affiliation: Cardiology Section, Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX, USA.
authors.forename: Gabriel B
authors.initials: GB
authors.lastname: Habib
authors.affiliation: Coordinating Center for Clinical Trials, Division of Biostatistics, University of Texas School of Public Health, Houston, TX, USA.
authors.forename: Sara L
authors.initials: SL
authors.lastname: Pressel
authors.affiliation: Clinical Trials Service Unit, University of Washington, Seattle, WA, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Probstfield
authors.affiliation: Renal-Hypertension Section, Veterans Affairs New Jersey Health Care System, East Orange, NJ, USA.
authors.forename: Sithiporn
authors.initials: S
authors.lastname: Sastrasinh
mesh_terms: D000367:Age Factors; D000368:Aged; D017311:Amlodipine / Q000008:administration & dosage* / Q000009:adverse effects; D002423:Cause of Death; D002752:Chlorthalidone / Q000008:administration & dosage* / Q000009:adverse effects; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D053208:Kaplan-Meier Estimate; D017706:Lisinopril / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012720:Severity of Illness Index; D012737:Sex Factors; D020521:Stroke / Q000175:diagnosis / Q000401:mortality* / Q000503:physiopathology / Q000517:prevention & control*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D017311:Amlodipine; D017706:Lisinopril; D002752:Chlorthalidone
keywords: ACE inhibitor; calcium channel blocker; diuretic; hypertension