When Pradax and Xarelto hit the market, they created huge buzz in the United States and Canada. The new medications were praised as a better alternative to warfarin, a blood thinner given to patients with atrial fibrillation, to reduce the risk of stroke.
Warfarin has long been used broadly since the mid-fifties, but requires frequent monitoring, can be negatively affected by certain foods and is generally difficult for many patients to take. The new drugs don't require regular monitoring. More importantly, they are heralded as superior to warfarin in reducing the risk of bleeding, notably in the brain.
"It's really a paradigm change," said Mathias Knecht, vice-president of medical affairs at Boehringer Ingelheim Canada, which sells Pradax.
But cracks are appearing in the feel-good story as reports emerge of health risks suffered by patients taking the new blood thinners.
A study published in January by researchers at the Cleveland Clinic in Ohio that examined several research trials involving Pradax found the drug was linked to a higher risk of heart attack than warfarin or enoxaparin, another blood thinner.
Last December, the U.S. Food and Drug Administration announced it was launching a safety review of the drug, sold as Pradaxa in that country, following reports of serious bleeding in people taking it.
In March, doctors from the University of Utah reported in the Journal of Neurosurgery the case of an elderly man taking Pradax who died of a massive brain hemorrhage following a routine fall. The doctors said the case suggested the blood-thinning effects of Pradax aren't easily reversible, whereas the effects of warfarin can be mitigated fairly simply.
The wave of studies was capped off by a contentious article published last month by Reuters – in which a dozen physicians expressed concerns over Pradax and Xarelto – which elicited heated debate.
Health Canada is conducting a safety investigation of the new drugs in light of these safety concerns, according to spokeswoman Christelle Legault.
The key question is: Do these reports represent the type of common safety issues that emerge once an innovative drug is introduced to a large population of patients? Or do they signal something more serious that could endanger patients' lives?
Health Canada had approved dabigatran in 2010, sold under the brand name Pradax, for people with atrial fibrillation. Earlier this year, a second new drug, rivaroxaban, sold under the brand name Xarelto, also received approval for atrial fibrillation, and a third competitor is expected on the market soon.
The efficacy of the new anticoagulants has major implications for the tens of thousands of Canadians who are on blood thinners to manage atrial fibrillation, the most common type of arrhythmia, which increases the risk of stroke up to fivefold. A rapid, irregular heartbeat can lead blood to pool in the heart's chambers, increasing the risk of clotting and stroke. The Heart and Stroke Foundation estimates that 350,000 Canadians have atrial fibrillation.
Doctors not involved in the development or clinical trials studying the new drugs, such as Allan Skanes, cardiologist at London Health Sciences Centre in London, Ont., say the benefits of the drugs appear to outweigh potential risks. "I would suggest there's no need for alarm," said Dr. Skanes, who co-chaired a Canadian Cardiovascular Society panel that wrote new guidelines for the treatment of atrial fibrillation in 2010.
Although research such as the Cleveland clinic study has indicated new blood thinners are linked to a slightly increased risk of heart attack, several cardiologists in Canada say it is too small to be of real concern. They feel that the evidence to the contrary is incomplete. They also note that research has shown the risk of death linked to new blood thinners is lower than it is for warfarin.
The champions of the new drugs say few people report adverse events linked to warfarin, including bleeding, because the drug has been available for so long that those types of problems are considered par for the course, and not talked about much. Whereas with new drugs, there is a lot of attention paid to adverse reports.
"What we don't want is to have the fear-mongering [that] these new agents are bad," said Jeffrey Weitz, professor of medicine and biochemistry at McMaster University. (Dr. Weitz was involved in the development of the new anticoagulants and has received financial compensation from drug companies, including Boehringer Ingelheim, which sells Pradax.)
"If you choose the right drug and the right dose, then these drugs [Pradax, Xarelto] can be superior to warfarin at preventing stroke," said Dr. Skanes.
A key point in bringing new drugs to market is how different patient populations respond to them, once they are in general use. It's not yet known whether doses need to be adjusted for individuals who are especially large, for instance, or how well the drugs will respond to people with other medical conditions, and won't be known till more patients start taking them.
William Geerts, a thrombosis specialist at Sunnybrook Health Sciences Centre in Toronto, said he's taking a cautious approach and doesn't want to liberally prescribe the new anticoagulants until more information about real-world experiences from patients is available.
"I don't know at the end of the day what the net effect is going to be, if society is going to be better or not," Dr. Geerts said. "That remains to be seen."