Medicines

Thiazide diuretics reduce fracture risk compared to other antihypertensives


A thiazide diuretic has outperformed other antihypertensives in terms of reduced risk of hip and pelvic fractures hospitalisations, a post hoc analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) has shown.

The US study of more than 22,000 patients found fractures were reduced by 21% in patients randomised to the thiazide diuretic chlorthalidone over the ACE inhibitor or calcium channel blocker lisinopril or amlodipine.

However, commenting on the findings, cardiologist Professor Leonard Arnolda told the limbic the effect was small but statistically significant.

“There is some rationale for this as the drug affects calcium extraction in the kidney but the effect is small. In this group, if you treat 300 people for five years, then you reduce the number of fractures from five to four,” he said.

Professor Arnolda, clinical director at the Illawarra Health and Medical Research Institute, said there were also other factors to consider before using chlorthalidone as a first-line therapy for hypertension.

Chlorthalidone is cheap and effective but not commonly used alone in Australia partly due to concern about its effect on diabetes and lipids in the long term.”

It was most often used in combination with an ACE inhibitor or angiotensin-receptor blocker, he said.

The results, consistent with a 24% reduction in fracture risk found in a 2011 Cochrane meta-analysis of observational studies, were not maintained after the eight-year follow-up.

In 16,622 participants followed for an additional five years post-trial, and with no constraints on medication choice, there was no significant difference in fracture risk between the three original treatment groups.

An invited commentary also in JAMA Internal Medicine said that despite some methodological limitations, the study appeared to confirm chlorthalidone was – ‘a preferred agent for cardiovascular prevention’ – was also ‘a preferred agent for fracture prevention’.

“We need to ensure that treatment is consistent with patient goals and preferences, and we need to monitor patients carefully, especially during the first several weeks of therapy,” the commentary said.

The study excluded early fracture events in the first year that were more likely to be related to falls associated with new antihypertensive medications than any effect on bone.

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