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Thiazides linked to lower fracture risk than other antihypertensives

By Bianca Nogrady
Thiazide diuretics may be associated with a reduced fracture risk compared with other antihypertensives, according to a large clinical trial published in JAMA Internal Medicine.

Secondary analysis of data from 22,180 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) showed patients randomised to the thiazide chlorthalidone had a 21% lower risk of hip or pelvic fracture compared with those treated with the calcium channel blocker amlodipine or the ACE inhibitor lisinopril.

When compared with lisinopril use separately, chlorthalidone was associated with a 25% reduction in fracture risk over the trial period (mean follow up 4.9 years), but when compared with amlodipine use separately, the reduction in fracture risk was not significant.

Chlorthalidone was also associated with a significantly lower risk of fracture in patients with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or more, those aged 65 years or over, those of a race other than black, or those who were overweight.

Further analysis of up to five additional years of follow up after the trial showed that the trend to reduction in fracture risk in the thiazide group persisted but was not statistically significant.

Commenting on the findings, Professor John Wark, Professor of Medicine at the University of Melbourne, said these were important data that strengthened previous observational data suggesting a lower fracture risk in patients treated with thiazide antihypertensives.

‘There are prior data suggesting that thiazides are better first line for older people with hypertension anyway, and this lends further support to that based on additional potential benefit, especially in people who have a recognised higher risk of fracture,’ said Professor Wark.

Professor Wark told Endocrinology Today that thiazides are known to have a renal calcium-retaining effect, which could also influence bone density through the parathyroid hormone.

Although the study was a quality randomised trial, Professor Wark stressed that it was a post-hoc analysis and was not placebo controlled.

‘The authors themselves draw attention to the uncertainty of fracture-related effects of these other medications so it could be that we’re looking at drugs that might have some negative or positive effects on fracture rate,’ he said, highlighting a need for prospective primary randomised trials to investigate this further.
JAMA Intern Med 2017; 177: 67-76.