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Anticoagulant Rivaroxaban Clears FDA Panel Hurdle

An FDA advisory panel has recommended the approval of rivaroxaban (Xarelto) for stroke prevention in patients with non-valvular atrial fibrillation, but the panelists raised questions about the methodology of the trial that compared the drug to the gold standard, warfarin (Coumadin).

A final decision on the drug is expected in November.

Rivaroxaban has been developed as a once-a-day oral medication that prevents clotting by inhibiting factor Xa, a key component in the generation of thrombin. It is one medication in a line of drugs trying to position themselves to replace warfarin, which has many contraindications and requires frequent blood draws for monitoring; the new drugs would not require frequent blood draws.

Panelists questioned whether ROCKET-AF—the trial that compared rivaroxaban to warfarin—was sufficient to show noninferiority, as only 55% of the patients on warfarin had international normalized ratio (INR) levels needed for stroke prevention.

Ian Jenkins, MD, assistant professor in the division of hospital medicine at the University of California at San Diego, says that rivaroxaban “will be an option for AF, but probably not my first choice.”

Another oral warfarin alternative—dabigatran, which inhibits thrombin—is already available, he notes. And dabigatran was found to be superior to warfarin, while rivaroxaban was only found to be noninferior. But Dr. Jenkins also notes that dabigatran and rivaroxaban have not been compared head-to-head.

“The low percent of therapeutic INRs in ROCKET-AF does concern me,” Dr. Jenkins adds, “but we have to remember that the patients who will benefit the most from these medications are the ones with difficult-to-control INRs anyway.”

He also explains that patients now doing well on warfarin don’t have a “great reason” to boost their costs by trying another drug.

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The Hospitalist - 2011(09)
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An FDA advisory panel has recommended the approval of rivaroxaban (Xarelto) for stroke prevention in patients with non-valvular atrial fibrillation, but the panelists raised questions about the methodology of the trial that compared the drug to the gold standard, warfarin (Coumadin).

A final decision on the drug is expected in November.

Rivaroxaban has been developed as a once-a-day oral medication that prevents clotting by inhibiting factor Xa, a key component in the generation of thrombin. It is one medication in a line of drugs trying to position themselves to replace warfarin, which has many contraindications and requires frequent blood draws for monitoring; the new drugs would not require frequent blood draws.

Panelists questioned whether ROCKET-AF—the trial that compared rivaroxaban to warfarin—was sufficient to show noninferiority, as only 55% of the patients on warfarin had international normalized ratio (INR) levels needed for stroke prevention.

Ian Jenkins, MD, assistant professor in the division of hospital medicine at the University of California at San Diego, says that rivaroxaban “will be an option for AF, but probably not my first choice.”

Another oral warfarin alternative—dabigatran, which inhibits thrombin—is already available, he notes. And dabigatran was found to be superior to warfarin, while rivaroxaban was only found to be noninferior. But Dr. Jenkins also notes that dabigatran and rivaroxaban have not been compared head-to-head.

“The low percent of therapeutic INRs in ROCKET-AF does concern me,” Dr. Jenkins adds, “but we have to remember that the patients who will benefit the most from these medications are the ones with difficult-to-control INRs anyway.”

He also explains that patients now doing well on warfarin don’t have a “great reason” to boost their costs by trying another drug.

An FDA advisory panel has recommended the approval of rivaroxaban (Xarelto) for stroke prevention in patients with non-valvular atrial fibrillation, but the panelists raised questions about the methodology of the trial that compared the drug to the gold standard, warfarin (Coumadin).

A final decision on the drug is expected in November.

Rivaroxaban has been developed as a once-a-day oral medication that prevents clotting by inhibiting factor Xa, a key component in the generation of thrombin. It is one medication in a line of drugs trying to position themselves to replace warfarin, which has many contraindications and requires frequent blood draws for monitoring; the new drugs would not require frequent blood draws.

Panelists questioned whether ROCKET-AF—the trial that compared rivaroxaban to warfarin—was sufficient to show noninferiority, as only 55% of the patients on warfarin had international normalized ratio (INR) levels needed for stroke prevention.

Ian Jenkins, MD, assistant professor in the division of hospital medicine at the University of California at San Diego, says that rivaroxaban “will be an option for AF, but probably not my first choice.”

Another oral warfarin alternative—dabigatran, which inhibits thrombin—is already available, he notes. And dabigatran was found to be superior to warfarin, while rivaroxaban was only found to be noninferior. But Dr. Jenkins also notes that dabigatran and rivaroxaban have not been compared head-to-head.

“The low percent of therapeutic INRs in ROCKET-AF does concern me,” Dr. Jenkins adds, “but we have to remember that the patients who will benefit the most from these medications are the ones with difficult-to-control INRs anyway.”

He also explains that patients now doing well on warfarin don’t have a “great reason” to boost their costs by trying another drug.

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The Hospitalist - 2011(09)
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The Hospitalist - 2011(09)
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Anticoagulant Rivaroxaban Clears FDA Panel Hurdle
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