Millions of Americans take blood thinners to prevent the formation of blood clots and stroke, including many people who have been diagnosed with atrial fibrillation, a heart rhythm disorder.
Yet despite the ability of anticoagulants to prevent dangerous blood clots and stroke, these drugs carry serious risks, too, including life-threatening bleeding. Analysis by the Institute for Safe Medication Practices found that the Food and Drug Administration received nearly 34,765 adverse drug event reports last year for anticoagulants taken orally; that included nearly 3,000 deaths and more than 9,500 adverse events — like hemorrhaging, or bleeding, in the head — severe enough to require hospitalization.
At present, the majority of patients who are prescribed anticoagulants take the drug called warfarin, also known by the brand names Coumadin and Jantoven, in pill form. The drug’s dosing is adjusted based on a blood test patients have done at least every other week to measure the effect of the drug. This is important because if the dosing is too high it can increase a patient’s risk of bleeds; if it’s too low, it won’t be as effective in preventing clots and stroke.
Despite being used since the 1950s, anticoagulants still carry serious risks for patients. The ISMP called anticoagulants “the highest risk outpatient drug treatment in older patients,” and noted in a recent quarterly report that risk is only growing with the approval of four new blood thinners since 2010. Those include dabigatran (brand name Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa). While the drugs offer improved ease of use — not requiring a regular blood test to guide dosing like warfarin — they’ve raised additional safety concerns.
[See: 10 Ways to Lower Your Risk of Stroke.]
Newer Blood Thinners Spark Safety Concerns
Dr. Curt Furberg, who serves as a medical advisor to ISMP, notes that with Pradaxa — the first of the newer anticoagulants, approved in 2010 — there’s wide variation in anticoagulation, or clot-preventing effect of the drug, depending upon the patient. Unlike with warfarin, the new anticoagulents, including Pradaxa, only come in one dose in the U.S., even though Pradaxa is approved in two different dosages in Europe. So while research finds that Pradaxa effectively prevents stroke for some patients, for others the dosing is too low and ineffective or, conversely, too high, increasing the risk of bleeding.
Furberg, a professor emeritus of public health sciences at Wake Forest School of Medicine, also notes concerns surrounding Xarelto, which was approved in 2011. Where the three other new blood thinners are taken twice daily, Xarelto is taken just once a day. Though a boon to convenience, the downside, Furberg says, is that the single dose is fairly high initially; this can raise the risk of bleeding. And then the level of the drug in a person’s blood drops quickly, he notes, diminishing the drug’s ability to protect against stroke — for which it’s taken. “If you’re a patient on Pradaxa or Xarelto, I think you should talk to your physician and ask whether the drug should be switched to a safer and more effective oral [anticoagulant],” Furberg says.
Sandy Walsh, a spokeswoman for the FDA, notes the agency is constantly examining safety data as it keep tabs on approved drugs. “Following the approval of Pradaxa, FDA received a large number of reports of bleeding among Pradaxa users,” she said in an email. In a study of Medicare beneficiaries, the agency found a lower risk of stroke and death but a higher risk of gastrointestinal bleeding associated with Pradaxa, compared to warfarin. “These results are consistent with observations from the large clinical trial used to approve Pradaxa,” Walsh says.
The ISMP contends that research leading to approval of oral anticoagulants was “riddled with serious flaws.” But in an FDA Clinical Perspective article, Dr. Ellis Unger, an office director in the Center for Drug Evaluation and Research, said: “The approvals of Pradaxa, Xarelto, Eliquis and Savaysa were based on large clinical trials where the rates of strokes and bleeding were carefully monitored and compared, and they caused no more bleeding than warfarin. In fact, two drugs, Eliquis and Savaysa, caused less bleeding than warfarin. Three of the drugs [Pradaxa, Eliquis and Savaysa] were superior to warfarin in preventing strokes and other important blood clots, and Xarelto was very similar to warfarin.”
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Other Risks and Variables to Consider
Dr. Oussama Wazni, director of the outpatient department in clinical cardiac electrophysiology at the Cleveland Clinic, says he prescribes all four drugs, as well as warfarin, to patients. Because there are many variables to consider, from a patient’s age to weight to kidney function — since the kidneys clear the newer anti-clotting medications — the decision of what drug to prescribe differs by patient, he emphasizes.
“I think the biggest potential risk is that patients may be on the wrong doses because now we cannot monitor these [with blood testing], and we don’t know if the patient is really anticoagulated,” Wazni says of the newer drugs. “When patients are under the therapeutic threshold, then they’re more likely to have a clinical event for which they are taking the drug to help prevent, like a stroke,” adds Dr. Joseph Fredi, a cardiologist and assistant professor of medicine at Vanderbilt University Medical Center in Nashville. “When they’re over the therapeutic threshold, they’re more likely to have bleeding.”
Fredi also notes that for patients who experience serious or life-threatening bleeding as a complication of taking newer anticoagulants, with the exception of Pradaxa, there’s no way to immediately reverse the drug’s effect. This is true, too, in the event a patient has another emergency, such as being involved in a car accident or requiring an emergency heart procedure; there’s no approved so-called reversal agent to quickly stop effects of Eliquis, Xarelto or Savaysa so blood can clot properly. That differs from bleeding caused by warfarin, which can be stopped in emergencies by health providers intravenously administering vitamin K, in addition to using blood products like fresh plasma. (Or to stop bleeding that’s less serious, a health provider may advise a patient to take vitamin K in pill form and cease taking warfarin.) Last October, the FDA granted accelerated approval to the drug Praxbind (idarucizumab) for use in patients taking Pradaxa (dabigatran) to be used during emergency situations when there is a need to reverse Pradaxa’s blood-thinning effects. The lack of a reversal agent to stop life-threatening bleeding caused by three of the new anticoagulants is a concern for some patients, and something that should be discussed with a doctor before taking one of those drugs, Fredi says.
Along with discussing safety concerns, providers say patients should also talk with their doctors about lifestyle factors and personal preferences. Clinicians say while some may feel more comfortable using warfarin because dosing can be adjusted and bleeding can be reversed, others — preferring not to have their blood drawn regularly, for example — favor newer anticoagulants. Experts advise all options should be discussed, rather than a doctor making that decision unilaterally. Fredi says one additional caveat is that among patients who have an artificial mechanical heart valve surgically implanted, such as to replace a diseased heart valve, only warfarin should be used. That’s because, he says, the use of any of the new oral anticoagulants for a mechanical heart valve does not protect patients from a blood clot forming on the valve.
[See: The Best Foods for Lowering Your Blood Pressure.]
Making a Decision About Anticoagulants
Though the need for many patients with clotting risk to take an anticoagulant is often clear, this is something that should be discussed before making any decisions about medications. That includes taking into account so-called risk scores, Fredi says. “So let’s say the patient seems to have a 7.5 percent annual risk of stroke, [and] the risk of serious life-threatening bleeding [from taking an anticoagulant] is 1.5 percent. It would make sense then that the risk is less than the benefit and the patient should be advised to take an oral anticoagulant,” he says. On the other hand, if the risk of stroke is really low, say under 1 percent, then there’s no strong data to support treatment with a blood thinner, he says — new or old.
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What You Should Know Before Taking New Blood Thinners originally appeared on usnews.com
