Risk of hospitalized gastrointestinal bleeding in persons randomized to diuretic, ACE-inhibitor, or calcium-channel blocker in ALLHAT

J Clin Hypertens (Greenwich). 2013 Nov;15(11):825-32. doi: 10.1111/jch.12180. Epub 2013 Aug 7.

Abstract

Calcium channel blockers (CCBs) are an important class of medication useful in the treatment of hypertension. Several observational studies have suggested an association between CCB therapy and gastrointestinal (GI) hemorrhage. Using administrative databases, the authors re-examined in a post-hoc analysis whether the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) participants randomized to the CCB amlodipine had a greater risk of hospitalized GI bleeding (a prespecified outcome) compared with those randomized to the diuretic chlorthalidone or the angiotensin-converting enzyme inhibitor lisinopril. Participants randomized to chlorthalidone did not have a reduced risk for GI bleeding hospitalizations compared with participants randomized to amlodipine (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.92-1.28). Those randomized to lisinopril were at increased risk of GI bleeding compared with those randomized to chlorthalidone (HR, 1.16; 95% CI, 1.00-1.36). In a post-hoc comparison, participants assigned to lisinopril therapy had a higher risk of hospitalized GI hemorrhage (HR, 1.27; 95% CI, 1.06-1.51) vs those assigned to amlodipine. In-study use of atenolol prior to first GI hemorrhage was related to a lower incidence of GI bleeding (HR, 0.69; 95% CI, 0.57-0.83). Hypertensive patients on amlodipine do not have an increased risk of GI bleeding hospitalizations compared with those taking either chlorthalidone or lisinopril.

Trial registration: ClinicalTrials.gov NCT00000542.

Publication types

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

MeSH terms

  • Aged
  • Amlodipine / adverse effects
  • Amlodipine / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use
  • Calcium Channel Blockers / adverse effects*
  • Calcium Channel Blockers / therapeutic use
  • Chlorthalidone / adverse effects
  • Chlorthalidone / therapeutic use
  • Diuretics / adverse effects*
  • Diuretics / therapeutic use
  • Female
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology*
  • Hospitalization*
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Incidence
  • Lisinopril / adverse effects
  • Lisinopril / therapeutic use
  • Male
  • Middle Aged
  • Myocardial Infarction / prevention & control*
  • Risk Factors
  • Treatment Outcome

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Diuretics
  • Amlodipine
  • Lisinopril
  • Chlorthalidone

Associated data

  • ClinicalTrials.gov/NCT00000542