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

J Am Soc Hypertens. 2014 Nov;8(11):808-19. doi: 10.1016/j.jash.2014.08.003. Epub 2014 Aug 19.

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.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aged
  • Amlodipine / administration & dosage*
  • Amlodipine / adverse effects
  • Cause of Death
  • Chlorthalidone / administration & dosage*
  • Chlorthalidone / adverse effects
  • Confidence Intervals
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypertension / diagnosis
  • Hypertension / drug therapy*
  • Hypertension / mortality
  • Kaplan-Meier Estimate
  • Lisinopril / administration & dosage*
  • Lisinopril / adverse effects
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Risk Assessment
  • Severity of Illness Index
  • Sex Factors
  • Stroke / diagnosis
  • Stroke / mortality*
  • Stroke / physiopathology
  • Stroke / prevention & control*
  • Survival Rate
  • Treatment Outcome

Substances

  • Amlodipine
  • Lisinopril
  • Chlorthalidone

Associated data

  • ClinicalTrials.gov/NCT00000542