UKidney Nephrology News and Insights

Thiazide diuretics are not created equal, especially with the new ARB azilsartan

imageMany studies have questioned the effectiveness of hydrochlorothiazide (HCTZ) versus chlorthalidone as a diuretic. In fact, most large scale trials that have used HCTZ have been disappointing (e.g. ACCOMPLISH) while those using chlorthalidone have been largely positive (e.g. ALLHAT). While this might seem like an over-simplification, many hypertension experts agree with it.

In the latest twist to this story, Takeda Pharmaceuticals have created a fixed dose combination with it's new ARB azilsartan with chlorthalidone - in stark contrast to all other ARB and ACE inhibitor counterparts. As it it turns out, they may be on to something ( continued ... )

A late-breaking trial presented at the American Society of Hypertension meeting shows that a fixed-dose combination product of azilsartan and the thiazidelike diuretic chlorthalidone had better antihypertensive effects than azilsartan and hydrochlorothiazide (HCTZ). This is the first double-blind study to compare the effects of the two diuretics, chlorthalidone and HCTZ, in combination with an ARB.

In the late-breaking trial, a 10-week, double-blind, multicenter, randomized study in just over 600 patients with moderate to severe primary hypertension, all patients received azilsartan 40 mg/day alone for the first two weeks. For weeks 3 to 6, they were then randomized to receive azilsartan 40 mg/day in a fixed-dose combination with chlorthalidone 12.5 mg/day (n=302) or azilsartan 40 mg/day coadministered with HCTZ 12.5 mg/day (n=303). From weeks 7 through 10, each diuretic was titrated to 25 mg/day "for the people who did not reach target BP," Bakris explained. Patients were followed for another month and for a further safety period of 12 weeks.

The primary efficacy end point was change from baseline to weeks 6 and 10 in trough sitting systolic BP assessed by the clinic measurement; "we had to bow to the FDA," Bakris commented. "Secondary end points, which may be more meaningful," were change from baseline to weeks 6 and 10 in 24-hour mean systolic BP assessed by ambulatory blood-pressure monitoring (ABPM), and safety end points, including adverse events and laboratory data.

Bakris made the point that not everybody got the highest dose of diuretic, but about 15% to 16% more people in the HCTZ group required this than in the chlorthalidone group (45.9% compared with 30.8%), "and that's important when we talk about the side effects as well."

Source: The

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