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

Academic Article


  • 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

    Digital Object Identifier (doi)

    Author List

  • Yamal JM; Oparil S; Davis BR; Alderman MH; Calhoun DA; Cushman WC; Fendley HF; Franklin SS; Habib GB; Pressel SL
  • Start Page

  • 808
  • End Page

  • 819
  • Volume

  • 8
  • Issue

  • 11