The Trouble with Anticoagulants

Providence, RIOne of the new classes of oral anticoagulants or blood thinners, Xarelto or Rivaroxaban, used to prevent strokes and blood clots in at-risk patients, is coming under increasing scrutiny.

Like Pradaxa, the other new major oral anticoagulant prescription medication, Xarelto is considered easier to administer to patients and requires less close monitoring than warfarin, a blood thinner that has been widely used to prevent strokes since 1954.

Xarelto, marketed by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, came on the market in 2011, one year after Pradaxa. Both medications are prescribed for patients with atrial fibrillation (AFib), a condition that causes an irregular heartbeat and creates a high risk for stroke.

A recent meta-analysis published in JAMA-Neurology looked at strokes, or intracranial hemorrhages (ICHs), in patients with AFib using the “newer anticoagulants” or NOACs.

Dr. Saurav Chatterjee, MD, Division of Cardiology, Brown University, and the lead author of the study, told LAS in an exclusive interview that the study found “NOACs are uniformly associated with an overall reduced risk of intracranial hemorrhage when used for stroke prevention in AFib patients.”

The study, however, did find that when compared to warfarin, there is a statistically significant but “mild increase in dyspepsia and gastritis,” says Dr. Chatterjee. “But many of these events may be clinically non-relevant,” he adds.

In addition, Dr. Chatterjee went on to say that “Rivaroxaban (Xarelto) does appear to increase rates of gastrointestinal bleeds in comparison with warfarin.”

One of the major concerns about both Pradaxa and Xarelto is that in the event of an uncontrolled hemorrhage there is no good way to stop the bleeding - a scenario that could turn deadly. In addition, the anticoagulant must be taken as directed and patients should never abruptly stop using the medication.

Dr. Chatterjee says that “Not having specific antidotes is obviously a big drawback - but there are trials ongoing, which are testing antidotes. For now, a reasonable alternative may be to administer recombinant factor VIIa, three-factor and four-factor prothrombin complex concentrate, and activated prothrombin complex concentrate and or fresh frozen plasma with acute bleeds.”

In January of 2013, The Institute for Safe Medication Practices (ISMP), a non-profit drug safety think tank, provided an update on Pradaxa and Xarelto in its Quarter Watch publication, which monitors serious adverse drug events reported to the FDA.

The authors of the ISMP report wrote, “Strong signals continued for the three anticoagulant drugs, warfarin (COUMADIN) and newcomers dabigatran (PRADAXA) and rivaroxaban (XARELTO). The three drugs accounted for 1,734 reports to the FDA in 2012 Q2, including 233 patient deaths, reinforcing the conclusion that the anticoagulants rank among the highest risk of all outpatient drug treatments.”

In an article in the print edition of Neurology, published on February 25, 2014, Dr. Antonio Culebras, a member of the American Academy of Neurology from the Upstate Medical University faculty in Syracuse, New York, wrote that “The World Health Organization reports atrial fibrillation (AFib) to be nearing epidemic proportions, affecting 0.5 percent of the population worldwide.”

Untreated, 1 in 20 patients will go on to have a stroke, according to the article.

The article went on to say that oral anticoagulants, including warfarin, are an important tool in preventing strokes in this population. Patients should be carefully monitored and uncontrolled bleeding is a risk.

Pradaxa has been the target of several thousand individual lawsuits in the US alleging the drug did more to cause blot clots than reduce them. In May 2014, the makers of Pradaxa agreed to pay $650 million to resolve lawsuits brought by 4,000 people across the US.

Several law firms are now researching or in the beginning stages of litigation against the makers of Xarelto. It is expected the suits will focus on drug injury or failure to warn issues.

Xarelto has annual worldwide sales of approximately $1.3 billion.