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

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.