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Randomized Controlled Trial
. 2014 Nov;8(11):808-19.
doi: 10.1016/j.jash.2014.08.003. Epub 2014 Aug 19.

Stroke outcomes among participants randomized to chlorthalidone, amlodipine or lisinopril in ALLHAT

José-Miguel Yamal  1 , Suzanne Oparil  2 , Barry R Davis  3 , Michael H Alderman  4 , David A Calhoun  2 , William C Cushman  5 , Herbert F Fendley  6 , Stanley S Franklin  7 , Gabriel B Habib  8 , Sara L Pressel  3 , Jeffrey L Probstfield  9 , Sithiporn Sastrasinh  10 ; ALLHAT Collaborative Research Group
Affiliations
Randomized Controlled Trial

Stroke outcomes among participants randomized to chlorthalidone, amlodipine or lisinopril in ALLHAT

José-Miguel Yamal et al. J Am Soc Hypertens. 2014 Nov.

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.

Trial registration: ClinicalTrials.gov NCT00000542.

Keywords: ACE inhibitor; calcium channel blocker; diuretic; hypertension.

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Conflict of interest statement

Conflicts of Interest/Disclosure Statements

Dr. Oparil has received honoraria from Daiichi Sankyo. Dr. Cushman has received honoraria from Takeda and Novartis. Dr. Probstfield has received honoraria from Sanofi. Drs. Alderman, Calhoun, Davis, Fendley, Franklin, Habib, Sastrasinh, and Yamal, and Ms. Pressel have no financial interests to report.

Figures

Figure 1
Figure 1
CONSORT diagrams: (A) Cohort 1 for in-trial stroke analyses; (B) Cohort 2 for in-trial and post-trial deaths after in-trial stroke analyses; (C) Cohort 3 for in-trial and post-trial strokes analyses. †Excluding incident stroke deaths with no prior stroke.
Figure 2
Figure 2
Forest plots of in-trial (Cohort 1 at 6-year) and in-trial and post-trial (Cohort 3 at 10 year) stroke outcomes by treatment group and subgroups. Abbreviations: A, amlodipine; afib, atrial fibrillation; C, chlorthalidone; CHD, coronary heart disease; CI, confidence interval; HR, hazard ratio; L, lisinopril;
Figure 3
Figure 3
In-trial blood pressure and stroke rates
See this image and copyright information in PMC

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