Diuretic-based antihypertensive therapy touted for obese

Dec 13 2012

By Caroline Price, Senior medwireNews Reporter

Diuretic-based antihypertensive regimens may be preferable to calcium channel blocker-based therapy in patients who are obese, suggest researchers writing in The Lancet.

The team carried out a prespecified subanalysis of the large ACCOMPLISH clinical trial and found that, whereas calcium channel blocker-based therapy was more cardioprotective than a diuretic-based regimen in normal weight and overweight patients, it offered no such advantage in obese patients, who had comparable cardiovascular (CV) event rates with each regimen.

"Diuretic-based regimens seem to be a reasonable choice in obese patients in whom excess volume provides a rationale for this type of treatment, but thiazides are clearly less protective against CV events in patients who are lean," write Michael Weber (State University of New York, USA) and colleagues.

The researchers say that hypertension in normal weight and obese patients may be mediated by different mechanisms, and suggest that the paradoxically higher CV event rates recorded for lean versus obese patients in hypertension trials may reflect the types of antihypertensives used.

However, authors of an accompanying editorial suggest that the current study was not adequately powered to draw firm conclusions in the obese group. They also suggest that any advantage in the obese group could relate to the cardioprotective benefit of diuretics in patients with heart failure - an effect that is disputed for calcium channel blockers - and that treatment decisions should therefore still be based on the primary indication.

Weber and colleagues' analysis of 11,482 participants in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial looked at the primary endpoint (a composite of cardiac and stroke events) according to patients' body mass index (BMI).

In patients allocated to the ACE inhibitor benazepril and thiazide diuretic hydrochlorothiazide, the primary endpoint rate was significantly higher among normal weight (BMI <25 kg/m²) than obese (BMI ≥30 kg/m²) patients. By contrast, CV outcomes did not differ according to BMI category in patients allocated to benazepril and the calcium channel blocker amlodipine.

Further analysis showed that treatment with benazepril and amlodipine was associated with significant 43% and 24% reductions in the risk for the primary endpoint compared with benazepril and hydrochlorothiazide among normal weight and overweight (BMI ≥25 to <30 kg/m²) patients, respectively.

However, the 11% estimated risk reduction with amlodipine versus hydrochlorothiazide seen in the obese group was not statistically significant.

Nonetheless, editorialists Franz Messerli (Columbia University College of Physicians and Surgeons, New York, USA) and Sripal Bangalore (New York University School of Medicine, USA) argue: "The analysis for the obese group had only 35% power (based on our own calculations) to detect a 15% difference between the two groups and the point estimate still favored amlodipine over hydrochlorothiazide."

Indeed, Messerli and Bangalore caution that diuretics may be contraindicated in obese people owing to the risk for new-onset diabetes. They conclude that the treatment decision should depend on the indication, with calcium channel blockers indicated for hypertension irrespective of body size, and diuretics indicated for left ventricular dysfunction irrespective of BMI.

"This strategy relegates diuretics to third-line agents for treatment of hypertension, except in patients at risk of heart failure - a position recognized in the latest UK guidelines," they conclude.

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