Blood thinners protect against stroke, but at a cost

Three stories of life on blood-thinning medication:

Matthew Klug of Avon-by-the-Sea, N.J., cut back on his beloved pastime of surfing when his doctor warned that if he hit his head, he could suffer internal bleeding.

Paul Cirielli of Montvale, N.J., stopped woodworking, leery of the sharp tools, and he also carries around a packet of special powder that can be applied to bad cuts to stanch the flow of blood.

And Arlene Geise of Miami has stopped taking blood thinners after a bout of severe gastrointestinal bleeding sent her to the hospital.

All three senior citizens were advised to take the drugs after periodic episodes of the abnormal heart rhythm called atrial fibrillation, meaning they were at higher risk of having a clot travel from the heart to the brain - a stroke. All are taking one of several newer anticlotting drugs and have become acquainted with a balancing act that millions face.

On one hand, a stroke can be incapacitating or fatal, and blood thinners, formally called anticoagulants, significantly reduce the risk. On the other hand, the drugs cause bleeding more easily.

That is an inconvenience in most cases, and physicians say it is well worth it, given the upside of protecting the brain. Bleeding can be managed, said Charles Paraboschi, a cardiologist at St. Mary Medical Center in Langhorne. But a stroke?

"As one of my partners says, you can virtually always give blood, but you can never give brain," said Paraboschi, also medical director of the anticoagulation clinic at Mercer Bucks Cardiology.

Still, each year a few patients out of every 100 end up with major bleeding, such as Geise, 77.

In 2013, she started taking the anticoagulant Xarelto, marketed in the U.S. by Janssen Pharmaceuticals, a unit of Johnson & Johnson.

All was good until last fall. Geise said she felt ill for several weeks, and one night in November, she awoke to find she was bleeding from her rectum.

"It's bright red, and it won't stop," she recalled.

She went to the emergency room and spent three days in the hospital, followed by two more days of returning for tests. Physicians blamed Xarelto and told her to quit, she said.

That drug - approved by the Food and Drug Administration in July 2011 for patients with atrial fibrillation not caused by a heart-valve problem - is one of four newer anticoagulants. The others are Pradaxa (approved in October 2010 for that purpose), Eliquis (December 2012), and Savaysa, approved Jan. 8.

All are designed to compete with warfarin, a drug developed more than 60 years ago. Patients on that medicine must have their blood tested every few weeks to make sure the drug is present at a safe and effective level.

The makers of the novel drugs tout that patients who take them need not undergo any such test. And studies indicate the new drugs are at least as effective at preventing strokes and are less likely to cause intracranial bleeding. Yet gastrointestinal bleeding, such as Geise suffered, may be more likely.

Some clinicians and patients are concerned the newer drugs do not have a "reversal agent" - an antidote that would stop bleeding in an emergency - but several such drugs are in development.

A study of one such drug, aimed at reversing the effects of Pradaxa, is being led by Pennsylvania Hospital's Charles Pollack, professor of emergency medicine at the University of Pennsylvania's Perelman School of Medicine.

Still, concerns remain.

The FDA approved Pradaxa in a one-size-fits-all dose of 150 milligrams, taken twice a day, even though its manufacturer, Boehringer Ingelheim of Germany, sought clearance for a lower 110-milligram dose in older patients at higher bleeding risk. (An even lower 75-milligram dose was approved for people with kidney problems, however.)

Evidence suggests the 110-milligram option would lower the risk of bleeding in older patients without increasing strokes, said Thomas J. Moore, senior scientist at the nonprofit Institute for Safe Medication Practices in Horsham.

FDA officials initially warned that if they approved the 110-milligram dose, it might be overused. Peter R. Kowey, chief of cardiovascular diseases at Main Line Health's Lankenau Heart Institute, called that "a paternalistic approach."

Kowey said he would attend an FDA meeting in February at which physicians and agency officials will discuss revisiting the 110-milligram issue as well as the development of reversal agents.

Concerns of bleeding also have prompted legal action. In May, Boehringer Ingelheim agreed to pay $650 million to settle lawsuits in which attorneys contended the company failed to provide adequate warning about Pradaxa's risks. Last week, a Philadelphia Common Pleas Court judge classified 75 cases against Janssen, the marketer of Xarelto, as a mass tort. And physicians predict suits against makers of the other new drugs will follow.

Geno Merli, co-director of the Jefferson Vascular Center and a professor at Jefferson University's Kimmel Medical College, worries the publicity around such cases could have an adverse effect.

"It's enough to get anyone nervous [so as] not to use the agent," he said.

Bad idea, said Kowey, who has consulted for several of the drug makers.

An estimated 3 million Americans suffer from atrial fibrillation, of whom half take no anticoagulant, he said.

"You've got to be on something," Kowey said, whether warfarin or a newer drug. "The strokes that you get with atrial fibrillation are not trivial events. They either kill you or you're in a nursing home."

So which to pick? The novel drugs can be pricey, with monthly out-of-pocket costs in the Philadelphia region ranging from $20 to more than $360, depending on coverage, according to the AARP's Public Policy Institute.

Yet they are winning converts in the market. Each has its own pluses and minuses, and a doctor's advice is key.

Cirielli, 65, of Montvale, tried Coumadin, the brand-name version of warfarin, and hated the frequent blood tests.

"You feel like an invalid," he said. He switched to Eliquis this month, in part because it is cleared quickly from the system, and he was concerned about the lack of an antidote. So far, no complaints.

Klug, 66, the surfer, has been on Xarelto since spring 2014. He maintains an active lifestyle, riding his bike and hitting the gym, but is more wary around his cat, Moose. A passing swipe of the claws, and he bleeds.

"It's like a balancing act," he said.

A balance between stroke and bleeding. For now, he'll take the latter.

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