Is the Novel Oral Anticoagulants’ (NOAC) purported effectiveness, worth their dangerous safety issues in the elderly population?
Just like many other senior Americans, Gloria Glatz, age 88, died in 2012 because of a severe complication caused by Xarelto side effects. Gloria Glatz suffered of atrial fibrillation, a condition associated with a significant risk factor for stroke, so in December 2011, her doctor prescribed her a new anticoagulant drug: Xarelto (rivaroxaban).
Together with other four new oral anticoagulants known as (NOACs), Xarelto was approved in 2010. The other NOACs, Eliquis (apixaban) and Pradaxa (dabigatran), were amply marketed as easier and more convenient than Warfarin and became a staple of the newer therapeutic approaches. The main difference between NOACs and Warfarin, is that the latter’s activity is antagonized by Vitamin K, so if a bleeding emergency happens, or prior to a surgical intervention, the administration of vitamin K can quickly revert its effects. There’s no known antidote to Xarelto instead, as packed red blood cells can just somewhat help mitigating its blood thinning action.
Gloria died on March 23, 2012, at a Kenosha hospital because of a gastrointestinal bleeding that doctors had no means to stop.
A vast MedPage Today/Journal Sentinel investigation showed that since 2010, almost 60,000 citizens have reported a life-threatening NOACs side effect, such as a severe bleeding accident. Since 2010, Warfarin-related bleeding accidents accounted for just 700 deaths: a much small number compared to the 8,000 victims caused by Pradaxa and Xarelto. Although newer NOACs represent just the 10% of all blood thinner drugs prescribed since 2010, 9 out of 10 of the deaths reported to the FDA voluntary adverse events reporting system are linked to them. The newer anticoagulant drugs are also way more expensive than the old ones. According to an analysis of Medicare data, in 2013 warfarin was dispensed about 6 times more than rivaroxaban and dabigatran together, but while the first cost taxpayers only $240 million, the other two were paid more than $1 billion.
One of the main advantages of NOACs is that they don’t require continuous INR testing like Coumadin (Warfarin) does. To avoid reducing Warfarin’s effectiveness by eating Vitamin K-rich foods, patients need also to undergo some dietary restrictions and avoid alcohol consumption. The MedPage Today/Journal Sentinel investigation cited above, discovered that Gregory Lip, the British doctor who ideated a new system for determining stroke risk that vastly increased NOACs sales, had extensive monetary ties to the pharmaceutical companies that produce these drugs. This new system was included into standard treatment guidelines written by U.S. and European leading medical societies that were also significantly financed by the same Big Pharma lobbies.
In 2013, a clinical study published in The American Journal of Cardiology showed that American patients that suffer from atrial fibrillation (Afib), increased their number from 3 million to over 5.2 million. Following the new guidelines, the number of patients that qualify for anticoagulant therapy jumped by one full million: from 3.7 million to 4.7 million, according to another scientific source found in the May volume of the JAMA Internal Medicine journal .
This incredibly larger number is due to the fact that following the new guidelines, virtually all women suffering from atrial fibrillation and almost all patients aged 65+ require this kind of therapy. The newer risk scale ideated by Gregory Lip, MD, to determine whether a patient should undergo anticoagulation therapy, is called the CHA2DS2-VASc. However, treating a patient with a low risk of a stroke with Xarelto or the other NOACs may be more harmful than beneficial because of the increased risk of an unstoppable bleeding accident which may endanger his or her very life.
Concerning dangers and serious side effects
Many concerns about dangerous, uncontrolled bleeding caused by NOACs side effects have been raised, though. A 2011 letter to the New England Journal of Medicine, a 2012 letter in the Journal of Neurosurgery, and a 2014 paper in a hematology journal, all described cases of patients who died or were rescued from the brink of death caused by internal bleeding provoked by NOACs side effects after small domestic accidents.
In May of 2014, American plaintiffs who allegedly were harmed after using Pradaxa (dabigatran), filed a lawsuit against German drug maker Boehringer Ingelheim, and the company agreed to pay $650 million to settle about 4,000 lawsuits. Newer Xarelto lawsuits keep being filed daily, as an entire army of specialized Xarelto lawyers is busy checking news cases.
One of the main selling points of NOACs is that these drugs showed a reduced risk in terms of brain bleeding accidents, and a small percentage increase in terms of stroke reduction. In the clinical trial that tested Eliquis, the ARISTOTLE-AF, that included 18,000 subjects, for example, brain bleeding accidents in patients under Eliquis treatment were just 0.3% of total cases, compared to 0.8% in patients who took warfarin. The number of strokes or blood vessel clots among Eliquis patients was just 1.3%, compared to a slightly higher 1.6% in warfarin patients.
In the famous ROCKET-AF trial, that included 14,000 patients, only 0.5% of those taking rivaroxaban suffered intracranial hemorrhage (ICH), against 0.8% of those under warfarin treatment.
That’s for bleeding accidents. But what about major bleeding accidents – i.e. the life-threatening ones including gastrointestinal hemorrhages? Here the numbers seem to swap: Warfarin only accounts for 5.4% cases, compared to Xarelto’s 5.6%. Although both Pradaxa and Xarelto seemed to show some benefits compared to Warfarin in terms of stroke reduction, some numbers still raised several concerns. For example in the RE-LY, the Pradaxa pivotal trial, 1.5% of patients under treatment with Pradaxa had a heart attack: a larger percentage than the 1.1% of those who took Warfarin.
Also, it should be noted how in both the RE-LY and ROCKET-AF trials, the FDA raised some question on whether warfarin was used in an appropriate way. As warfarin levels need to be constantly monitored to keep coagulation levels within the appropriate range, it was discovered that during these trials, researchers compared the newer drugs with patients with uncontrolled levels of warfarin. As soon as their values were appropriately monitored, a later FDA review showed how all the benefits showed in the Pradaxa trial actually disappeared. The same happened in similar FDA reviews about Xarelto, as the trial was conducted in several countries around the world, including ones like India that didn’t use warfarin well enough, leading to a bias in favor of the NOACs. An FDA review even recommended against the approval of rivaroxaban for Afib as it was considered too dangerous. Also, many of the doctors who wrote the newer guidelines on NOACs, or worked as co-authors during these trials, worked in their past as speakers or consultants for these same companies that produce them.
Article written by: Dr. Claudio Butticè, Pharm.D.
Last Updated: 2016/08/21