Thiazide-type diuretics may reduce risk of hip, pelvic fractures in adults with hypertension

After nearly five years of follow-up, adults with hypertension who received chlorthalidone had a 21 percent lower risk of hip and pelvic fractures compared with those who received lisinopril or amlodipine, according to a post hoc analysis of a randomized trial.

Chlorthalidone is a thiazide-type diuretic, amlodipine is a calcium channel blocker and lisinopril is an ACE inhibitor.

Lead researcher Rachel Puttnam, MD, of Kaiser Permanente of Georgia in Atlanta, and colleagues published their results online Nov. 21 in JAMA Internal Medicine.

The researchers analyzed data on 22,180 participants from the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study that compared medications to treat hypertension. The trial found that amlodipine, lisinopril and doxazosin mesylate were not superior to chlorthalidone in preventing fatal coronary heart disease or nonfatal MI as well as other major cardiovascular disease or renal outcomes.

The participants were at least 55 years old, had a systolic blood pressure of at least 140 mm Hg and/or a diastolic blood pressure of at least 90 mm Hg or took medication for hypertension and had at least one additional risk factor for coronary heart disease. The mean age was 70.4 years old, while 43 percent of participants were female and 49.9 percent were white.

In this secondary analysis, the researchers obtained fracture data from the Centers for Medicare & Medicaid Services and Veterans Affairs hospitalization data from Feb. 1, 1994, through 2006.

During the follow-up period, 34 participants had pelvic fractures and 307 participants had hip fractures. Three participants had both a pelvic and hip fracture.

Unadjusted and adjusted analyses found that participants who were randomized to receive chlorthalidone had a significantly lower risk of fractures compared with the lisinopril and amlodipine groups.

Participants in the chlorthalidone group had a 25 percent lower risk of fracture compared with the lisinopril group and an 18 percent lower risk of fracture compared with the amlodipine group.

The researchers noted that during the trial and follow-up period, the cumulative incidence of fractures was lowest in the chlorthalidone group, but the difference was not statistically significant.

“Our analyses based on posttrial and in-trial experience were not based on a randomized comparison and thus are subject to bias,” the researchers wrote. “Moreover, during the posttrial period, the choice of blood pressure medication was no longer constrained by the study protocol; therefore, those originally randomized to receive chlorthalidone might have stopped using this medication and non-chlorthalidone users might have begun to take a thiazide diuretic.”

The study had a few limitations, according to the researchers, including that the results were conducted post hoc and subject to unmeasured bias. The ALLHAT study also excluded participants who were at high risk for fracture, including those with coronary artery disease, heart failure and chronic kidney disease. In addition, the researchers relied on databases instead of medical records and did not have information on participants eligible for Medicare who were enrolled in managed care.

“The present results of short-term and long-term fracture protection with thiazide antihypertensive therapy compared with other antihypertensive medications strongly recommend use of a thiazide for hypertension treatment in addition to its long track record of cardiovascular protection,” the researchers wrote.