How dangerous are the Novel Oral Anticoagulants?

How dangerous are the Novel Oral Anticoagulants?

Xarelto (rivaroxaban) is a Novel Oral Anticoagulant (NOAC) medication manufactured by Bayer and Janssen Pharmaceutical, that promised to change forever the blood-thinner medications scenario with a new “user-friendly” formula. The new drug was in fact marketed as “safer” and “easier to use” than its much older counterparts, Warfarin, and other anti-platelet drugs, as it did not require continuous blood monitoring in specialized blood clinics. Xarelto was also allegedly superior to other similar medications as it did not require the user to endure dietary restrictions, reduce alcohol consumption, and increased compliance with its easy “one pill per day” formula. However, later findings and researches performed after Xarelto was marketed in 2011, found that this medication is also associated with significant risks and dangers. In our other articles we already thoroughly explained how Xarelto is in fact related to an increased danger of bleeding accidents and strokes. Also, Xarelto side effects are even more dangerous as there’s no antidote available to reverse this medication’s potentially lethal effects. Several Xarelto lawsuits have been filed against Janssen Pharmaceutical by patients (or their relatives) who were negatively affected by its adverse reactions, including internal bleeding, severe hemorrhages, brain stroke, gastrointestinal bleeding and even death.

What about the other two Xarelto-closely related drugs Eliquis (apixaban) and Pradaxa (dabigatran)? Are all NOACs equally dangerous as Xarelto is? The main issue with all the NOACs is the fact that if a patient experiences a bleeding event, doctors have few options to treat him and save his life, as there’s no known reversal agent available for these medications. With other blood thinners such as Warfarin or Clopidogrel instead, an intravenous infusion of vitamin K or fresh platelets is sufficient to halt the bleeding event. The unique mechanisms of action of NOACs (direct thrombin inhibition, or direct coagulation factor Xa inhibition) prevent their action from being stopped by Vitamin K. However their respective manufacturers are actively researching some antidotes.

Pradaxa (dabigatran) – the first NOAC to kill patients

Pradaxa was first marketed by Boehringer Ingelheim in 2010, and it’s the first NOAC to be presented as a superior blood thinner compared to the older ones. It was approved for the prevention of blood clots in hip and knee surgery patients first, and then for prevention of stroke in patients with non-valvular atrial fibrillation. Just one year after its launch, in 2011 more than 540 patients died because of Pradaxa, according to the Food and Drugs Administration (FDA) and Institute for Safe Medication Practices (ISMP) reports, accounting for a total of 3,781 serious adverse events such as hemorrhage, acute renal failure, and stroke. Pradaxa side effects reports surpassed all other monitored drugs for the year, but at the same a total of approximately 1.1 million Pradaxa prescriptions were dispensed in less than one year, hitting $1.5 billion sales in 2012 no matter the consequences.

Many people filed federal lawsuits against Boehringer Ingelheim, which were then consolidated on August 2012, into a multidistrict litigation (MDL) in the U.S. District Court for the Southern District of Illinois, presided by U.S. District Court Judge David Herndon. In May 2014, the pharmaceutical company agreed to pay $650 million to settle all 4,000 state and federal Pradaxa lawsuits, yielding an average of $150,000 for each plaintiff. Just a few months later, on July 2014, a series of investigations were published in the British Medical Journal (BMJ). Investigators accused Pradaxa’s manufacturers of withholding crucial information about the importance of continuous monitoring of the medication’s blood levels. An adequate screening of Pradaxa’s plasma levels could, in fact, prevent patients (especially the elderly population) from suffering its severe side effects such as the potentially lethal internal bleedings. Pradaxa blood levels did vary from patient to patient, similarly to what happens with Warfarin, but the company prevented both the FDA and the European Medicines Agency (EMA) from accessing this data for financial reasons.

 

Eliquis (apixaban) – the “Younger brother” of the NOACs family

Eliquis was the third NOAC approved in the United States by FDA in 2012, and it’s produced by Pfizer and Bristol-Myers Squibb. Eliquis was approved for the prevention of stroke in people with atrial fibrillation, and the prevention and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). However, back in 2012, a FDA reviewer, Dr. Thomas Marciniak, MD, noted how critical data involving several patients’ deaths was missing. Data from more than 300 patients that participated in the trial was in fact omitted, pushing up the statistical significance of the result in order to portray Eliquis as safer and less deadly than its counterpart Warfarin. In June 2015, the first federal lawsuit against Eliquis was filed after a 60 years old patient died of a gastrointestinal bleeding that doctors weren’t able to stop. The lawsuits accuse Bristol-Myers Squibb of cutting costs and hiring incompetent agents during the large ARISTOTLE study that led to the approval of Eliquis from FDA. Among the alleged claims, the pharmaceutical companies were deemed guilty of “changing and falsifying records, including records disappearing just before the FDA made a site visit, reportedly on the order of an employee of BMS.”

A few months ago, In July 2015, the Wall Street Journal and the Bloomberg reported Eliquis’ approval was stalled and delayed by the FDA for nine months as they found several problems in a large portion of the data coming from the Chinese clinical trial site. The final-stage trial of apixaban involved some 18,000 Asian patients, with at least 30 sites located in China. In a study site, the records were improperly manipulated, while in others a large percentage of the patients received either the wrong dose of the blood thinner or the wrong drug altogether. According to the regulatory agency, many documents were inappropriately (or fraudulently) manipulated, with unreported adverse events, missing medical outcomes, and patients records disappearing after the agency sent their inspectors in Shanghai.

Article written by: Dr. Claudio Butticè, Pharm.D.

Published: 2015/12/18
Last Updated: 2016/09/16