NEW YORK: For millions of heart patients, a pair of new blood thinners have been heralded as the first replacements in 60 years for warfarin, a pill whose hardships and risks have deterred many from using the stroke-prevention medicine.
But growing complaints of risks and deaths tied to the new crop of drugs have made some top US cardiologists hesitant to prescribe them. Some are proposing a more rigorous monitoring regimen for when they are used.
Most concerns revolve around Pradaxa, a twice daily pill from Boehringer Ingelheim that was approved by the USFood and Drug Administration in October 2010 to prevent strokes in patients with an irregular heartbeat called atrial fibrillation. It was the first new oral treatment for that use since warfarin was introduced in the 1950s.
"The good news is you now have an alternative to warfarin," said Dr. Alan Jacobson, director of anti-coagulation services at the Veterans Administration (VA) healthcare system in Loma Linda, California. "The bad news is you can kill a patient as easily with the new drug as you could with the old drug" if it is not handled properly.
"The average patient doesn't understand anything about the new drug, or what the risks are, or what other medicines he can or can't take," said Jacobson, citing interactions with common painkillers and other drugs that can alter Pradaxa blood levels.
Xarelto, a once daily pill that Johnson & Johnson developed with Bayer AG, was approved last November for atrial fibrillation. The condition affects about 3 million Americans, causing blood to pool in a storage chamber of the heart, where it can clot and travel to the brain.
Both new drugs were designed to sidestep risks of warfarin, including brain hemorrhages and other dangerous bleeding, and become mainstays of a new therapeutic market worth at least $10 billion a year. Patients taking warfarin require close monitoring and regular blood tests as well as dietary and lifestyle changes.
Doctors have less data and familiarity with Xarelto, which is still being rolled out.
But Jacobson and another dozen physicians interviewed by Reuters expressed similar concerns about both Pradaxa and Xarelto.
They say that real world use of Pradaxa and Xarelto, which do not require regular blood monitoring or frequent doctor follow-up, raises concerns about the risk of stroke, serious bleeding and blood clots if not taken properly, particularly in patients with poor kidney function.
The nonprofit Institute for Safe Medication Practices estimated last month that 542 reports of deaths associated with Pradaxa were reported to the FDA in 2011, topping all other medicines, including warfarin, with 72 deaths. Adverse event reports on Xarelto were not available.
A case study published in March raised alarm in particular, showing an elderly Utah patient on Pradaxa developed a massive brain hemorrhage and died after a minor fall.
European regulators have instructed Boehringer Ingelheim to add warnings about the bleeding risk to Pradaxa's package insert. Almost two dozen U.S. federal lawsuits have been filed against Boehringer Ingelheim alleging harm from Pradaxa.
Boehringer declined to comment on the lawsuits. The German company also declined to comment about the deaths, but said the number of reports of bleeding with Pradaxa were within Boehringer's expectations, given the incidence of bleeding seen in the drug's largest study.
"Research has shown that the number of reported adverse events for a drug peaks during its first few years on the market," when doctors are most likely to file voluntary reports to regulators and drugmakers, company spokeswoman Emily Baier said.
Dr. Robert Temple, a top official in the FDA's Center for Drug Evaluation and Research, said few doctors notify the agency about incidents from warfarin because its risks are already well known. So the lopsided number of Pradaxa reports compared with warfarin may not indicate an elevated risk, he said.
"We don't necessarily believe it is real," he said. "But we're watching it. We can't help but notice it."
A shift in practice
The makers of Pradaxa and Xarelto say it takes time for doctors to get up to speed on new types of treatments and how to best administer them outside the controls of clinical trials.
"This is a shift in medical practice," said Dr. John Smith, senior vice president for clinical development at Boehringer. "Individual physicians have to determine what the follow-up plan will be, to use common medical-sense judgment."
Dr. Peter Wildgoose, a senior director of clinical development at J&J, said the company has not provided special advice on follow-up care for patients on Xarelto.
"There's nothing more than for any other drug that people regularly take," he said, adding that most atrial fibrillation patients probably see their doctors on a regular basis. "These drugs have been tested long term, for several years at a time, with very good outcomes."
Boehringer Ingelheim and Johnson & Johnson officials stressed there was far less evidence in trials of brain bleeding - the most worrisome side effect of anti-coagulants - in patients taking Pradaxa and Xarelto than those taking warfarin.
In the meantime, warfarin is holding its own, with 33 million U.S. prescriptions filled for atrial fibrillation and other uses last year, according to IMS Health, a healthcare information and services company. Some 2.2 million prescriptions were filled for Pradaxa.