A famous Xarelto commercial markets it as a safe drug that’s helping many Americans live their lives happily without the need for blood clinic check-ups and dietary restrictions. But what about its dangerous side effects? Are Bayer AG and Janssen Pharmaceutical telling us the truth about their overhyped drug in their advertisement, or are they just promoting a harmful drug that could threaten the very life of many U.S. citizens?
Xarelto (Rivaroxaban) is a Novel Oral Anticoagulant (NOAC) marketed in the United States Xarelto by Janssen Pharmaceuticals and Bayer AG. This drug’s prescription saw a distinct rise in the last couple of years, allowing it to become the first among its competitors. As other blood thinners, rivaroxaban prevents dangerous blood clots from forming and growing within our body, and it is mainly indicated for the reduction of risk of stroke in patients with non-valvular atrial fibrillation, and the treatment of pulmonary embolism (PE) and Venous Thromboembolism (VTE) (1). The market is full of many other similar blood-thinners that were used for many years, such as Plavix (clopidogrel), heparins and most of all Coumadin (warfarin). All these blood thinners were, in fact, quite effective in treating patients, and some of them were used safely for more than 40 years.
Why the urge to develop a new medication then? First of all, due to their mechanism of action, many of these drugs do interact with other alimentary sources of Vitamin K, such as broccoli, kale or spinach, forcing the patient to endure specific dietary restrictions. Another very important limitation is the fact that Warfarin needs a continuous monitoring of its effectiveness, to assess properly its safety by continuously adjusting its dosage. This control is usually performed in a doctor’s office or clinic, although some home monitoring kits do exist. Thanks to their novel mechanism of action instead, NOACs like Xarelto do not require either particular dietary regime limitations or annoying trips to a patient’s GP’s office to monitor their effectiveness (2, 3).
The main downside of all anticoagulants, though, is that they are all associated with a distinct risk for serious adverse reactions like hemorrhages and internal bleeding. Even a small accident like a fall can pose a serious threat to a patient’s life. However, if the patient is treated quickly enough, his life can be saved by an immediate infusion of fresh platelets (a specific blood cell type) or intravenous Vitamin K. The same cannot be said for Xarelto and the other NOACs instead, as there’s no antidote to save the patients from their life-threatening side effects. For example, Pradaxa (dabigatran), another NOACs very closely related to Xarelto, accounted for 3,781 adverse events in 2011, including 542 patient deaths, surpassing all other regularly monitored drugs in reports of hemorrhage (2,367 cases), acute renal failure (291), and stroke (644) (4). Several other studies also found that rivaroxaban and the other NOACs were also related to an increased risk of bleeding and that their safety profile is not so safe as it was initially believed (4, 6). Xarelto side effects include easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), bleeding from wounds or needle injections, any bleeding that will not stop, but as no antidote is available. Even gastrointestinal bleeding ulcers may prove to be fatal. All NOACs were deemed high-risk medications by several international agencies, including the FDA who advised caution with the use of these drugs (7, 8).
The Xarelto advertisement and TV commercials
Xarelto and the other NOACs are widely commercialized and advertised as the improved standard of care for VTE, thanks to their “superior efficacy”, “simple dosing” and in what could be considered as one of the most blatant lies of modern marketing, a “favorable safety profile”. Several friendly-talking Xarelto commercials featured famous VIPs like the American racing driver Brian Vickers, the comedian Kevin Nealon and one of the greatest golfers of all time: Arnold Palmer. They all happily spoke about their love for golf and life itself, and how this drug improved their quality of life with no blood monitoring and no dietary restriction required. Sitting on a cozy wooden bench on their golf course, Nealon throws his punchline while speaking to his newly acquired Xarelto-mates: “Golf clinic or blood clinic? Ooh, that’s a tough one”. But what if one of them takes a fall and starts bleeding when no antidote is available to save their life?
Maybe the punchline should be “Emergency room or morgue? Ooh, that’s a tough one”.
So are really NOACs providing a better alternative to patients that must undergo anticoagulation therapy? And how high is their cost, not only in terms of additional accidents and deaths but in terms of simpler monetary expenditure? Looking at the statistics, the numbers are literally breath-taking. Xarelto costs about $3,000 a year per patient, compared with just $200 for warfarin. Since they were first marketed in 2010, all the newer anticoagulants were rapidly adopted everywhere, quickly substituting warfarin, a medication that was safely used for several years. A review published in The American Journal of Medicine showed that in 2013 NOACs accounted for 62% of all new anticoagulant prescriptions (and we’re talking about a market where at least 15 competitors are present). But the most significant fact is that they account for 98% of total anticoagulant-related drug costs. The cost itself is no small time money too. Citing a study lead by Niteesh K. Choudhry, MD, PhD:
“Average combined patient and insurer anticoagulant spending in the first 6 months after initiation was more than $900 greater for patients initiating a novel anticoagulant”.
Another finding that raises many additional questions is the fact that among patient with lower CHADS2 (Congestive heart failure, Hypertension, Age >75 years, Diabetes mellitus, Stroke) and HAS-BLED (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly [Age >65 years], Drugs/alcohol concomitantly) scores were those associated with the highest odds of receiving a NOACs prescription (9). What does it mean in simpler terms? It means that these drugs are deliberately used on the low-risk profile patients, whose number is significantly higher than the high-risk patients. And it’s quite easy to do some math and understand how big is the Big Pharma’s revenue coming from Xarelto, as the current market for anticoagulants is estimated to be worth $10 billion. In 2014, some 4,000 lawsuits were filed against the German pharmaceutical company Boehringer Ingelheim accounting them responsible for several deaths and serious bleeding accidents caused by their drug Pradaxa. Eventually, they agreed to pay a fine of $650 million to settle the litigations. Although they claimed that they did pay as the litigation diverted too many resources and time from patient care and newer research, it’s clear enough how that was just small money compared to their estimated revenues (10).
Article written by: Dr. Claudio Butticè, Pharm.D.