Slippery Slope: Does Convenience Trump Safety With NOACs?

http://www.medpagetoday.com/special-reports/slipperyslope/52867

At 88-years-old, Gloria Glatz still embraced life.

The mother of three was an avid Scrabble player and made a phenomenal potato salad in between occasional visits to the casino.

Like as many as 5 million Americans, Glatz had atrial fibrillation, a known risk factor for stroke.

In December 2011, her doctor decided it was time to put her on an anticoagulant drug, but rather than choosing the decades-old standby, warfarin, the doctor prescribed Xarelto (rivaroxaban), which had been approved by the U.S. Food and Drug Administration just a few months earlier.

Xarelto is one of four anticoagulants approved since 2010 that make up a class of drugs known as novel (or newer) oral anticoagulants, NOACS (pronounced No-aks) for short. Widely promoted as more convenient than warfarin, the drugs came to market with much fanfare anticipating blockbuster status.

But unlike warfarin, which is a vitamin K antagonist that can be turned off in a bleeding emergency or prior to surgery by administering vitamin K, all of the NOACs were approved without an antidote, although packed red blood cells can slow their anticoagulation action.

When Glatz developed gastrointestinal bleeding, months after she started taking Xarelto, doctors could not make it stop. She died March 23, 2012 at a Kenosha hospital.

“They said there was nothing they could do,” said her daughter, Dottie Glatz.

Convenience: Yes, Antidote: No

Since 2010, more than 58,000 people have reported a serious side effect, such as a major bleeding episode, after using one of the anticoagulants designed to replace warfarin, a MedPage Today/Milwaukee Journal Sentinel investigation found.

At least 8,000 deaths have been linked to three of the new anticoagulant drugs since 2010, compared with about 700 for warfarin. Mortality data for the fourth drug, approved in January, is not yet available.

These numbers are drawn from the FDA’s adverse events reporting system, which is largely voluntary. Though the reports are not verified, the numbers suggest an imbalance: the three newer drugs accounted for less than 10% of all anticoagulant prescriptions, yet they were linked to more than 90% of deaths reported to the FDA since 2010.

Doctors are increasingly prescribing the newer, more expensive drugs to people with afib as a way to prevent strokes and also for short term use for both prevention and treatment of deep vein thrombosis (DVT).

A primary selling point to the drugs is that they don’t require regular INR testing. With warfarin, also known as Coumadin, patients must have regular INR testing, which can be done at a doctor’s office, an anticoagulation clinic, or can be monitored with home testing.

Patients must also follow dietary measures, such as not eating large or inconsistent amounts of foods that are rich in Vitamin K, which can lessen warfarin’s effectiveness. That includes spinach, kale and brussels sprouts.

Alcohol also should be limited to small amounts.

Marketing campaigns highlight the convenience of the new drugs, including a recent TV ad for Xarelto featuring comedian Kevin Nealon, who has atrial fibrillation, and golfer Arnold Palmer and NASCAR driver Brian Vickers, who both had blood clots in their legs.

The three sit at a table at a golf course.

“Let’s see, golf clinic or blood clinic?” Nealon says. “Ooh, that’s a tough one.

More than 10 million prescriptions for the new drugs, costing about $3.5 billion, were dispensed in 2014, according to data from IMS Health, a market research firm. Prescriptions for warfarin, which is a fraction of the price, went down slightly in 2014 compared with 2013 and 2012.

The NOAC Boom

The surge in use of the drugs has been bolstered by a new system for determining stroke risk that was devised by a British doctor who, the MedPage Today/Journal Sentinel investigation found, has extensive financial ties to companies that make or market the new drugs.

The new system was adopted as part of treatment guidelines by leading medical societies in the U.S. and Europe — ones that themselves have received millions from drug manufacturers.

In addition, many of the doctors who wrote those guidelines or issued other recommendations had personal financial ties to those companies, such as working as speakers or consultants.

Some 5.2 million Americans have atrial fibrillation, according to a 2013 paper published in The American Journal of Cardiology. That’s higher than past estimates of about 3 million.

How many qualify for an anticoagulant under the new guidelines?

Applying new scale, the number of Americans deemed in need of an anticoagulant jumped overnight from an estimated 3.7 million to 4.7 million, according to a paper published in May in the journal JAMA Internal Medicine.

Rita Redberg, MD, a cardiologist and editor of JAMA Internal Medicine, said she tells patients to wait a few years until the true risks and benefits of the new drugs are known.

“I don’t prescribe any of the newer oral anticoagulants,” said Redberg, a professor of medicine at the University of California, San Francisco. “My concern is that a lot of the people being put on the novel oral anticoagulants will have more harm than good.”

The new drugs have proven to be an expensive alternative to warfarin, now a generic, which remains more frequently used.

In 2013, taxpayers paid more than $1 billion for prescriptions of just two of the drugs, Xarelto and Pradaxa (dabigatran), according to an analysis of Medicare data. Warfarin was  dispensed about six times more often, but cost taxpayers significantly less — $240 million.

The data for 2013 are the most recent available.

Filed under: General Problems