Digoxin Side Effects May Increase Risk of Death When Used With Xarelto: Study

The findings of yet another new study appears to indicate that side effects of the heart drug digoxin may increase the risk of death in patients with atrial fibrillation (AF).

Researchers from Duke University looked at clinical trial data on patients given digoxin along with the blood thinner Xarelto, and found that the drug was linked to an increased risk of all-cause mortality, vascular death and sudden death in AF patients. The findings were published on March 5 in the medical journal The Lancet.

The study looked at data collected by the ROCKET AF clinical trials, which were used to help approve the blood thinner Xarelto, which has itself been linked to reports of serious and potentially deadly bleeding side effects.

Researchers found that during the trial 5,239 patients, about 37% of participants, were given digoxin for ventricular rate control. They used the data from the Xarelto trial because of a lack of randomized trial data involving digoxin use in AF patients.

The study found a 17% increased risk in all-cause mortality, a 19% increased risk in vascular death, and a 36% increased risk in sudden death among patients given digoxin, compared to those who were not. They also found that patients were more likely to be female, have a history of heart failure, diabetes, and persistent atrial fibrillation.

“This association was independent of other measured prognostic factors, and although residual confounding could account for these results, these data show the possibility of digoxin having these effects,” the researchers concluded. “A randomized trial of digoxin in treatment of AF patients with and without heart failure is needed.”

Concerns About Digoxin Side Effects

Similar conclusions have been raised in a number of previous studies that looked at the risk of death among heart patients, including AF patients, who have been prescribed digoxin.

In November 2014, a study published by the medical journal Circulation: Arrhythmia and Electrophysiology found that AF patients faced a 71% higher risk of death and a 63% higher risk of hospitalization when given digoxin.

In September 2014, researchers from Duke University found that digoxin increased the risk of death by 22% in patients with atrial fibrilliation. That study was presented at a conference in Barcelona, and researchers said that there need to be extensive randomized clinical trials to determine the risks and benefits of digoxin.

The Duke University study came on the heels of findings published in the Journal of the American College of Cardiology in August, which found those prescribed digoxin were 26% more likely to die over the next four years. That translated to 95 deaths per 1,000 person-years for those given digoxin, compared with 67 per 1,000 person-years among those not given the heart drug.

Researchers from the United Kingdom came to similar conclusions in a study published in the European Heart Journal in November 2012, examining data on 4,000 patients. The study found that there was a 41% increased risk of death among AF patients given the digoxin.

In a study published in June 2010, side effects of digoxin were linked to an increased risk of death among patients undergoing dialysis treatment, with the findings suggesting that the risk was dose-related, with higher rates of death found among dialysis patients given hire doses of the drug.

More recently, a study published in the medical journal Circulation: Cardiovascular Quality and Outcomes in September 2013, found that heart failure patients given digoxin were more likely to die than other patients.

Digoxin Overdose Risks

Digoxin is commonly used to treat congestive heart failure, abnormal heart rhythms, atrial flutter and atrial fibrillation.  The medication is extremely dose-specific with a narrow therapeutic index.

If too little of the drug is prescribed it can be ineffective, and if too much is prescribed, it can lead to a digoxin overdose, where the drug builds up in the system. This can result in a serious and potentially life-threatening condition known as digitalis toxicity.

In April 2008, Actavis Totowa issued a Digoxin recall for all lots of its generic version, Digitek, after it was discovered that some tablets may have been commercially released that were twice as thick as they were supposed to be. The error potentially exposed thousands of users to a risk of digoxin overdose or poisoning.

According to a December 2008 report released by the non-profit Center for Public Justice, the FDA received reports of at least 667 digoxin overdose deaths tied to the recalled pills between April 2008 and June 2008.

Xarelto Health Concerns

The blood thinner Xarelto itself has been linked to health risks, particularly cases of uncontrollable bleeding. Xarelto (rivaroxoaban) is a new-generation anticoagulant introduced in 2011 as a superior replacement for Coumadin (warfarin), which has been the “go-to” medication for prevention of blood clots and strokes among patients with atrial fibrillation for decades.

While all blood thinners carry a risk of bleeding injury, Xarelto has been linked to a surprising number of problems as more and more patients are switched to the novel anticoagulant.

Xarelto has been promoted as superior to warfarin, with the drug makers indicating that it is easier to use since it does not require regular blood monitoring. However, several recent studies have raised questions about those claims, with researchers suggesting that Xarelto blood monitoring may actually help doctors identify patients at the greatest risk of bleeding.

The drug makers now face a growing number of Xarelto lawsuits, which allege that inadequate warnings were provided for consumers and the medical community about the bleeding risk, importance of blood monitoring an the lack of a reversal agent, which doctors could use to stop hemorrhaging that may develop among users.

While warfarin’s blooding thinning effects can be quickly reversed in an emergency, there is no antidote for Xarelto currently available. This has left many doctors unable to control bleeds, increasing the risk of severe injury or death.

In December 2014, a panel of federal judges ordered the centralization of all Xarelto bleeding lawsuits, transferring cases filed throughout the federal court system to one judge in Louisiana for coordinated pretrial proceedings.