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

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 Heart.org

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