番茄社区

WASHINGTON -- In back-to-back hearings, polypill advocates failed to light a fire under an FDA advisory committee, which rejected a hypertension combo and sent supporters of a three-drug polypill aimed at prevention of acute events back to the drawing board.

That was one of the key take-away messages from the meeting of the held on Wednesday.

The FDA focused on the polypill concept for 2 days this week -- starting Tuesday with a review of an NDA for a combination of beta-blocker and angiotensin receptor blocker -- nebivolol/valsartan. By a narrow 6-to-4 margin the committee members voted not to recommend approval for that combo.

Committee member , consulting professor of medicine for the Stanford University School of Medicine, in Stanford, Ca., said the polypill "did not have a robust enough effect." Susan Leighton, a patient representative from Huntsville, Ala., agreed, saying, "drugs need to deliver a clinical benefit."

cardiology service chief for Parkland Memorial Hospital in Dallas, said in voting no that physicians might prescribe nebivolol/valsartan when other more effective drugs are available, thereby shortchanging patients.

Committee members voting to recommend the drug for FDA approval acknowledged that the polypill's effects were minimal, but they argued that even a minimal effect over time could result in significant benefits, ultimately reducing the risk of heart attacks and stokes. One committee member said he did not "see any harm" in recommending the drug for approval, adding that it "makes sense" to put nebivolol/valsartan together.

On Wednesday, the committee took up a more theoretical discussion addressing the potential for a fixed-dose polypill that included an antihypertensive, aspirin, and a statin.

Proponents of this polypill approach argue that it would offer a less expensive, and more patient-friendly way to reduce cardiovascular risk across populations versus the one drug, one pill polypharmacy approach, which many clinicians say reduces adherence.

During Wednesday's meeting, the committee looked at three key issues when addressing the use of a polypill for cardiovascular health -- efficacy, formulation, and intended population for the drug. Although the committee did not reach a consensus on any of these issues, committee members raised some important points.

For example, several members said it would be helpful to have evidence that the formulation works across all population groups, particularly women and minorities, and whether it is, in fact, an appropriate substitution for single drugs on the market. They also said it would be important to know if there are any contraindications with the polypill.

Committee member , professor of medicine within the Department of Nephrology at Vanderbilt University School of Medicine in Nashville, Tennessee, said the polypill could result in unforeseen consequences. Patients, for example, may not realize what drugs they are taking with the polypill and, as a result, physicians may end up prescribing one of the medications in the polypill, giving patients a double dose of the same medication.

Patient advocate Leighton, meanwhile, wondered whether patients would look at the polypill as some sort of panacea that would reduce their risk of cardiovascular disease without requiring lifestyle changes.

The committee was supposed to focus on the effects of the polypill on secondary, not primary prevention. But three of the seven presentations presented to the committee addressed the use of the polypill in primary prevention, resulting in discussions about its use as a primary prevention tool.

For example, , a professor at the Wolfson Institute of Preventive Medicine at Barts and the London School of Medicine and Dentistry and one of the inventors of the polypill, said it should be offered to people over the age of 50 without contraindications as a preventive measure to reduce the risk of heart attacks and strokes. In this way, the polypill would serve more as a vaccine than actual therapy, Wald said in an interview with 番茄社区.

Wald presented data from a showing that 33% of the people who received the polypill starting at the age of 50 reduced their risk of heart attack or stroke through 8 years of follow-up.

In another presentation, Salim Yusuf, MD, DPhil, said the polypill should be part of an overall health systems strategy that seeks to simplify regimens and thereby improve adherence.

But even on the point of adherence members did not entirely agree. While it was generally acknowledged that simpler regimens are likely to lead to greater adherence, some committee members said more studies are needed to study the adherence issue because it is not entirely clear why some patients are nonadherent.

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