The effect of treatment based on a diuretic (indapamide) +/- ACE inhibitor (perindopril) on fractures in the Hypertension in the Very Elderly Trial (HYVET)

Age Ageing. 2010 Sep;39(5):609-16. doi: 10.1093/ageing/afq071. Epub 2010 Jun 23.


Background: fractures may have serious implications in an elderly individual, and fracture prevention may include a careful choice of medications.

Design: the Hypertension in the Very Elderly Trial (HYVET) was a double-blind placebo-controlled trial of a thiazide-like diuretic (indapamide 1.5 mg SR) with the optional addition of the angiotensin-converting enzyme (ACE) inhibitor (perindopril 2-4 mg). Fracture was a secondary end point of the trial.

Setting: HYVET recruited participants from Eastern and Western Europe, China, Australasia, and Tunisia.

Subjects: all participants were > or =80 years of age and hypertensive.

Methods: participants were randomised to receive a thiazide-like diuretic (indapamide 1.5 mg SR) +/- ACE inhibitor (perindopril 2-4 mg) or matching placebos. Incident fractures were validated and analysed based on time to first fracture.

Results: there were 3,845 participants in HYVET and a total 102 reported fractures (42 in the active and 60 in the placebo group). When taking only validated first fractures, 90 were included in the analyses (38 in the active and 52 in the placebo group). Cox proportional hazard regression, adjusted for key baseline risk factors, resulted in a point estimate of 0.58 (95% CI 0.33-1.00, P = 0.0498).

Conclusions: despite the lowering of blood pressure, treatment with a thiazide-like diuretic and an ACE inhibitor does not increase and may decrease fracture rate.

Trial registration: NCT00122811.

Publication types

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

MeSH terms

  • Aged, 80 and over
  • Aging*
  • Antihypertensive Agents / administration & dosage*
  • Antihypertensive Agents / adverse effects
  • Blood Pressure / drug effects
  • Drug Combinations
  • Female
  • Fractures, Bone / epidemiology
  • Fractures, Bone / prevention & control*
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Incidence
  • Indapamide / administration & dosage*
  • Indapamide / adverse effects
  • Male
  • Perindopril / administration & dosage*
  • Perindopril / adverse effects
  • Placebos
  • Risk Factors


  • Antihypertensive Agents
  • Drug Combinations
  • Placebos
  • indapamide, perindopril drug combination
  • Indapamide
  • Perindopril

Associated data