Azilsartan medoxomil-chlorthalidone fixed combination superior at reducing blood pressure

September 11, 2012

A fixed-dose combination of azilsartan medoxomil plus chlorthalidone (Edarbyclor, Takeda) was statistically superior to azilsartan medoxomil coadministered with hydrochlorothiazide at reducing and maintaining systolic blood pressure, according to the results of a phase 3 study published online August 31 in The American Journal of Medicine.

A fixed-dose combination of azilsartan medoxomil plus chlorthalidone (Edarbyclor, Takeda) was statistically superior to azilsartan medoxomil coadministered with hydrochlorothiazide at reducing and maintaining systolic blood pressure (SBP), according to the results of a phase 3 study published online August 31 in The American Journal of Medicine.

This study demonstrates the likelihood that a higher percent of hypertension patients will be able to be controlled with these two drugs in combination than with the standard therapy, according to study co-author William C. Cushman, MD, professor of preventive medicine at the University of Tennessee College of Medicine in Memphis, Tenn.

Researchers at The University of Chicago Medicine in Chicago conducted the randomized, double-blind, titrate-to-target blood pressure trial comparing the single-pill combination of azilsartan medoxomil-chlorthalidone versus azilsartan medoxomil coadministered with hydrochlorothiazide in 609 patients with stage 2 primary hypertension. The average baseline clinic blood pressure was 164.6/95.4 mm Hg.

“We know that [azilsartan medoxomil-chlorthalidone] combination is very effective compared with placebo and compared with another angiotensin II receptor blocker-hydrochlorothiazide combination,” Dr. Cushman said. “What this study did was to look at how the combination of the same dose of azilsartan would do combined either with chlorthalidone or with hydrochlorothiazide to see if there, in fact, is a difference in efficacy and how well blood pressure is lowered.”

All patients (n=609) received azilsartan medoxomil (40 mg) alone for 2 weeks and then 12.5 mg of either chlorthalidone or hydrochlorothiazide for 4 weeks (up to week 6). Patients were titrated to 25 mg for another 4 weeks (up to week 10) if they failed to achieve target blood pressure, which was defined as clinic blood pressure <140/90 mm Hg for participants without diabetes or chronic kidney disease or <130/80 mm Hg for participants with diabetes or chronic kidney disease.

Primary end point data showed a statistically significant reduction in clinic SBP at week 6 for patients taking the fixed-dose combination of azilsartan medoxomil and chlorthalidone (-35.1 mm Hg) compared with those patients taking azilsartan medoxomil and hydrochlorothiazide (-29.5 mm Hg). Further, those patients taking the fixed-dose combination of azilsartan medoxomil and chlorthalidone maintained a greater reduction in SBP at week 10 (-37.8 mm Hg) compared with those taking azilsartan medoxomil and hydrochlorothiazide (-32.8 mm Hg).

At the end of both 6 and 10 weeks, more patients taking the fixed-dose combination of azilsartan medoxomil and chlorthalidone achieved their target blood pressure versus those taking azilsartan medoxomil and hydrochlorothiazide (64.1% vs. 45.9% and 71.5% vs. 62.3%, respectively).

Management of hypertension can be complex and a large percentage of patients require multidrug therapy, Dr. Cushman added.