Monotherapy treatment with chlorthalidone or amlodipine in the systolic blood pressure intervention trial (SPRINT)

J Clin Hypertens (Greenwich). 2021 Jul;23(7):1335-1343. doi: 10.1111/jch.14296. Epub 2021 Jun 2.


This post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) examined the performance of chlorthalidone (C) versus amlodipine (A) monotherapies. ANOVA was used to analyze the differences in systolic blood pressure (SBP) response between C and A. Logistic regression was used to examine monotherapy failure (adding a second antihypertensive agent or switching to a different antihypertensive agent) rates. Four hundred ninety-one participants were treated with C monotherapy (n = 210, mean dose = 22 mg/day) or A monotherapy (n = 281, mean dose = 7 mg/day). There was a significant difference in mean SBP reduction between the C and A monotherapies at the third visit (higher reduction with A, adjusted p = .018). Unadjusted analysis showed a higher failure with C in the standard treatment group. Although the average SBP at failure was higher and above the 140 mm Hg cutoff that indicated monotherapy failure with A (142.60) compared with C (138.40), more participants on C failed despite having SBP below the 140 cutoff. This was probably due to decisions made by the investigative teams to change the antihypertensive regimen, because, in their opinion, the clinical picture required it. After adjusting for baseline characteristics, C had higher failure than A only in the standard treatment group (1.64 odds ratio [OR], 95% CI 1.06-2.56, p = .028). A sub-analysis including participants who had never used antihypertensive treatment before randomization had similar results (2.57 OR, 95% CI 1.34-5.02, p = .004). Overall, in SPRINT chlorthalidone was associated with higher monotherapy failure than amlodipine in the standard treatment group because of decisions of the investigative teams.

Keywords: SPRINT; amlodipine; chlorthalidone; hypertension; monotherapy.

Publication types

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

MeSH terms

  • Amlodipine / pharmacology
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure
  • Chlorthalidone* / pharmacology
  • Humans
  • Hypertension* / drug therapy
  • Treatment Outcome


  • Antihypertensive Agents
  • Amlodipine
  • Chlorthalidone