Bayer Healthcare says rivaroxaban’s development costs amount to more than $1.5 billion.
“I think all of them are promising,” says Shaun Mickus, a Johnson & Johnson spokesman. “We’re looking at meeting unmet medical needs. We have patients who, for one reason or another, are having blood clots in these indicated areas, and some of them are doing fine and getting the help they need, and others may not be.”
Boehringer spokeswoman Anna Moses said dabigatran is on formulary with 70% of the top 1,600 hospitals in the U.S.
“Our current focus is on efforts to educate physicians and payors about the product, including its efficacy, safety, and appropriate use,” Moses said in an email.
“[These are] drugs that don’t require monitoring, drugs that have very little drug-drug interaction, and drugs that have no food interaction; a drug where you give a fixed dose and the patients get the same effect anticoagulation-wise.”–Geno Merli, MD, FHM, director of the Jefferson Center for Vascular Disease and CMO at Thomas Jefferson University Hospital in Philadelphia
Warfarin’s Way Out?
Data on Pradaxa for stroke prevention in nonvalvular atrial fibrillation might be encouraging, but to some experts, it’s not automatically going to prove to be a superior alternative to warfarin, says Ian Jenkins, MD, assistant professor in the Division of Hospital Medicine and part of the VTE prevention team at UC San Diego.
“It is, statistically, significantly better than warfarin for nonvalvular atrial fibrillation when you look at the stroke rate, but the number needed to treat is not small—it’s 172 patients a year,” Dr. Jenkins says. “So, as far as looking at an individual patient and saying, ‘Am I going to prevent a stroke in this person by switching them to dabigatran?’ it’s actually unlikely that you would. And depending on the type of institution you’re at and how good they are at managing warfarin, you might be able to get a similar improvement in their stroke risk by, say, improving the quality practices for warfarin use at your hospital.”
“I think a lot of people are reluctant to start it on people who are doing well on warfarin,” Dr. Maynard adds. “There’s a lot of people who have been fine for many years on warfarin, even though it’s a tricky drug.”
At Thomas Jefferson, Pradaxa’s use is restricted to cardiologists, hematologists, and the hospital’s vascular anticoagulation service, and a doctor outside those categories has to get a consult first, Dr. Merli says. At University of Utah Healthcare, off-label uses have to be funneled through the thrombosis service, Dr. Pendleton says.
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Warfarin’s Many Medical Contributions Have Strange Origins
The standard in anticoagulation therapy for 50 years, warfarin might not have been discovered if a farmer hadn’t sought help for his dying cattle.
In February 1933, farmer Ed Carlson drove through a blizzard to Madison, Wis., stopped biochemist Karl Paul Link on the campus of the University of Wisconsin, and told him that sweet clover hay disease was causing his cattle to bleed to death. Link’s advice was perfunctory: have the cattle avoid eating spoiled hay.
But after the farmer’s visit, Link’s “senior student” persuaded him to try to find the agent within spoiled sweet clover hay that was causing the hemorrhaging effects. Link’s work eventually led to warfarin, a derivative of Coumadin, the substance that gives sweet clover its sweet smell. The name is a combination of WARF, which stands for Wisconsin Alumni Research Foundation, and coumarin. It was first used as a rodenticide.
Faith grew that the compound would not be fatal to people when, in 1951, an army inductee tried to commit suicide using the rat-killing compound. But he was unsuccessful, and his bleeding was reversed with doses of vitamin K.
By then, Link had perfected warfarin sodium and it was first made available for widespread clinical use under the trade name Coumadin sodium.
Howard Bremer, a retired patent attorney for WARF who still does consulting work for the foundation, says warfarin made $4 million for the foundation during the patent period from 1952 to 1972 (about $20 million in today’s dollars).
Money isn’t the main point, though, he says. “All the inventors are dead, the royalties long since ceased to flow to WARF with the expiration of the patents that were licensed,” Bremer says. “And here it still is the number-one anticoagulant utilized in cardiovascular programs worldwide.”
Thrombosis experts say that warfarin will still play a big role in anticoagulation treatment even as new drugs hit the market, in part because of familiarity and because some indications will not be studied right away.
“For all of its limitations and complexities, it has absolutely and markedly improved healthcare for patients with those disorders,” Dr. Pendleton says. “It took a long period of time to understand how to use warfarin appropriately and in what patients and at what dose. I think there will be—although different—similar challenges with the new drugs.”—TC