Salt May Lower ARB Efficacy in Diabetics

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SAN FRANCISCO—Dietary salt supplementation may reduce the antihypertensive effects of the angiotensin receptor blocker (ARB) telmisartan in patients with type 2 diabetes and hypertension, investigators reported at the 68th Scientific Sessions of the American Diabetes Association. The effect is independent of habitual sodium dietary status.

 

The findings come from a study of 32 hypertensive type 2 diabetics. George Jerums, MD, director of endocrinology and professorial fellow at the University of Melbourne in Australia, and colleagues assessed the effects of acute dietary salt supplementation on the antihypertensive effects of ARB blockade used as monotherapy or in combination with a thiazide diuretic.

 

“There is evidence that the addition of a diuretic potentiates renin angiotensin system (RAS) inhibition in hypertension not related to diabetes, and we also have evidence that dietary sodium restriction reduces blood pressure,” Dr. Jerums said. “Some articles suggest that these effects may be additive.”

 

Trial participants were selected on the basis of prior or habitual urinary sodium excretion. Patients were classified as habitual high dietary sodium (HDS) users if they had urinary sodium excretion greater than 200 mmol/day for two out of three consecutive measurements.

 

Patients were classified as habitual low dietary sodium (LDS) users if they had urinary sodium excretion less than 100 mmol/day for two out of three consecutive measurements.

 

During a six-week washout period, patients' usual antihypertensives were replaced by verapamil, prazosin, methyldopa, or hydralazine, with a treatment BP target of 140/90 mm Hg. Patients then received telmisartan 40 mg/day for four weeks with the addition of hydrochlorothiazide 12.5 mg/day over the next four weeks.

 

During the second two weeks of each treatment period, patients were randomized to receive capsules containing either placebo or salt 100 mmol/day. After a second six-week washout period, the regimen was repeated, with groups receiving placebo and salt supplementation reversed.

 

Results showed that an increase in sodium excretion of about 50 mmol/day approximately halved the BP response to telmisartan with or without hydrochlorothiazide. Additionally, when the HDS and LDS groups were combined, daily salt supplementation of 100 mmol/day resulted in a 3.5 mm Hg increase in mean arterial pressure.

 

“Thus, the addition of salt results in a 35% reduction in the effectiveness of antihypertensive therapy with an ARB,” Dr. Jerums said.

 

“Our results imply that acute increases in salt intake—for as short a time as two weeks—may blunt the antihypertensive effects of RAS blockade whether the patient had a history of high salt use or low salt use,” he added. “Thus, the data raise the possibility that long-term increases in salt intake may interfere with the effectiveness of antihypertensive therapy with ARBs.”

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