FDA advisory committee backs combination drug for first-line therapy

The FDA’s Cardiovascular and Renal Drugs Advisory Committee voted unanimously in favor of recommending approval of a new indication for irbesartan-hydrochlorothiazide as initial treatment of hypertension.

The drug (Avalide, Bristol-Myers Squibb, AstraZeneca) is a fixed-dose combination of the angiotensin receptor blocker irbesartan (Avapro; Bristol-Myers Squibb) and hydrochlorothiazide. It is currently approved for second-line use in hypertensive patients with BP uncontrolled by monotherapy, according to the FDA.

“I see no reason why fixed-dose combinations such as Avalide should not be approved for first-line therapy,” said Franz H. Messerli, MD, director of the hypertension program in the division of cardiology at St. Luke’s-Roosevelt Hospital in New York. “I’m talking about pretty much all fixed combinations in hypertension, not only the ones that we have so far that are diuretic-based combinations.

“It has been clearly documented that the faster you get to your treatment goal, the better the outcome and the more MIs and strokes you’ll prevent,” said Messerli, who is the Hypertension and Vascular Disease section editor of Today in Cardiology.

Investigating first-line use

Thomas D. Giles, MD, a professor of medicine at the Tulane University School of Medicine in New Orleans, presented his rationale for initiating therapy with fixed-dose combination hypertension drugs to the committee. He said that patients who use these treatments gain early control of BP with fewer adverse events.

Combination therapy also has an economic benefit because it requires fewer copayments and office visits and reduces health care costs. Giles said that combination drugs can bring hypertension under control more quickly than single agents and provide for better patient adherence, therefore leading to improved outcomes.

“Multidrug combinations often produce greater BP reduction at lower doses of the component agents, resulting in fewer adverse events,” Giles said. “The use of fixed-dose combinations may be more convenient and simplify the treatment regimen.”

The committee reviewed the data and said that the studies presented were well done, consistent and helpful in sorting through the issues. The committee voted to recommend expanding the drug’s indication; however, the committee questioned whether this expansion should be indicated only for patients with severe hypertension or for those with moderate and severe hypertension as well.

The committee also discussed the use of a hypertensive combination drug among patient subsets and those with comorbid conditions such as chronic kidney disease, congestive HF, CAD and diabetes. They said additional research is needed to expand on use in the elderly populations specifically those aged 70 years and older, and those with renal dysfunction.

“Avalide’s indication is similar to Hyzaar (hydrochlorothiazide combined with losartan potassium, Merck). So far, there are several drugs available as fixed combination that show benefit and can be started as initial therapy in hypertension; Avalide is one of them,” Messerli said.

The FDA expects to make a decision concerning the new indication in mid-August.

Dr. Messerli is a paid consultant for Merck, AstraZeneca and Bristol Myers Squibb.