When Pradaxa (dabigatran) was approved by the FDA in 2010 it was hailed as a “major milestone” in reducing the risk of strokes for patients with the irregular heart rhythm called atrial fibrillation (A-fib). Prior to Pradaxa, doctors relied primarily on warfarin (Coumadin) to prevent blood clots ending up in the brain.
Warfarin is an old drug. It’s been around for over 50 years. But this anticoagulant requires careful monitoring. Too much warfarin could lead to hemorrhage. Too little could allow blood clots to form. Patients are required to have regular blood tests to make sure there isn’t too much or too little medicine circulating in their bodies. Dosage adjustments are not unusual. There are nine different Coumadin pills ranging in dose from 1 mg to 10 mg.
Pradaxa was considered a breakthrough by some because it was marketed primarily as “one dose fits all” with no monitoring necessary. In other words, Pradaxa was supposed to be far easier to take than warfarin because dosing was easy and blood tests weren’t required. In one TV commercial a daughter and father are looking at a laptop computer together. Here’s a partial transcript from that commercial for Pradaxa:
Daughter: “My dad has atrial fibrillation or A-fib. He has the most common kind. It’s not caused by a heart valve problem. Dad, it says your A-fib puts you at five times greater risk of stroke.”
Dad: “That’s why I take my warfarin every day.”
Daughter: “It looks like maybe we should ask your doctor about Pradaxa.”
Voice Over: “In a clinical trial Pradaxa, dabigatran etexilate mesylate, was proven superior to warfarin at reducing the risk of stroke and unlike warfarin with no regular blood tests or dietary restrictions…”
The notion that patients on this blood thinner would not need regular blood tests or dosage adjustments was very appealing to physicians and patients. Sales took off! According to an editorial in the journal BMJ, co-authored by Blake Charlton, MD and cardiologist Rita Redberg, MD:
“Dabigatran achieved blockbuster status, with sales of over $1bn [billion] globally by April 2012 and $2bn in the US by 2014 despite increasing concerns about safety. By December 2011 adverse drug event databases in Europe, Japan, and the US showed thousands of serious and fatal hemorrhages in patients taking dabigatran, particularly older patients.”
A series of articles in the BMJ (July 24, 2014) reveal a tale of woe and intrigue surrounding Pradaxa. Questions have been raised about the accuracy and transparency of the clinical trial data used in the approval process. Concern about the FDA’s handling of the controversy is also emerging. Dr. Redberg describes it this way:
“The FDA issued a reassuring ‘drug safety communication’ after data from its pilot electronic surveillance programme (Mini-Sentinel) indicated that dabigatran’s risks were less than warfarin’s. However, a recent meta-analysis of randomized controlled trials examining risk of gastrointestinal bleeding with warfarin and dabigatran reached the opposite conclusion…These concerns, taken together with the observed incidence of major haemorrhage show the risk data are evolving and that the risks of dabigatran could be larger than previously reported.”
One of the most significant findings from the BMJ probe of Pradaxa may be the revelation that blood tests to monitor the anticoagulant effect of this drug could improve both its safety and effectiveness. That message, known by company executives, was allegedly kept from regulators in the US and Europe. It presumably would have undermined a key selling point that no blood testing was necessary with Pradaxa compared to warfarin.
The BMJ investigative report suggests that if doctors initiated regular blood monitoring and dosage adjustments with Pradaxa, they could reduce the risk of serious bleeding events. In May 2014, the manufacturer of Pradaxa agreed to pay $650 million to settle about 4,000 lawsuits involving the drug, many of which involved bleeding complications.
The People’s Pharmacy Perspective
Pradaxa has been promoted to doctors and patients as a simpler, safer and more effective anticoagulant than warfarin. We’re not convinced. For one thing, patients vary tremendously in how much Pradaxa gets into their bloodstreams. Blood testing would reveal valuable information that could optimize dosing and treatment and hopefully reduce risk of major bleeding episodes.
Older people are far more susceptible to hemorrhage from Pradaxa. They need a lower dose than the 150 mg capsules approved and recommended by the FDA. European regulators, concerned about reports of excessive bleeding, approved a 110 mg dose of Pradaxa, particularly for older patients.
What’s a patient to do? First, DO NOT STOP Pradaxa! Doing so could actually trigger a blood clot that could lead to a stroke. Do bring the BMJ articles to your doctor’s attention. Links are below:
Discuss these articles with your physician and their relevance to your situation.
Here are some comments form visitors to this website about the new generation anticoagulants. Share your own experience with anticoagulants in the comment section below.
“I am thoroughly confused as to why these new anticoagulants are being prescribed so freely by cardiologists. I have had 2 cardiologists and 1 electro-physiologist recently suggest I switch from Coumadin to Xarelto. A neurosurgeon I also saw said, ‘NO WAY!’ He has seen patients bleed to death before they could be treated for stroke or aneurism.
“My main concern is that there is no antidote for bleeding with Xarelto. What to do? How do you decide between two unpleasant options? What does one do if there is a bleed when on Xarelto? I’m very concerned.
“The doctors in favor of the new drug brush off my requests of what to do about bleeding problems and can’t seem to give me a straight answer. And all 3 cardios said Xarelto is the drug THEY would take. I don’t get it. By the way, Xarelto is considerably more expensive than warfarin or Coumadin. If a person is doing well on this drug, I don’t know why we should change. (I am having no problem with my current Coumadin!)” S.W.G.
“The prescription drug Pradaxa (dabigatran etexilate mesylate) is a medication which has been prescribed to hundreds of thousands of patients to thin their blood, thereby reducing the risk of stroke and blood clots when they have certain heart conditions such as atrial fibrillation.
“Warfarin (brand names include Coumadin, Jantoven, and Uniwarfin) has been on the United States market since about 1954. This well-known anticoagulant continues to be commonly prescribed to patients who are at risk of blood clots, which can lead to serious consequences such as stroke and death. Warfarin has been proven to be quite effective, and relatively safe (based on a risks and benefits analysis that considers the serious consequences of not anticoagulating patients at high risk of clotting).
“To maintain safety while taking warfarin, a patient must allow blood levels to be tested about every three months (to make sure there is not too much or too little in a patient’s system) and avoid foods rich in vitamin K (such as many leafy green vegetables), which can render warfarin ineffective. Failure to take warfarin exactly as prescribed and to monitor warfarin levels can lead to uncontrolled bleeding, which, if not treated emergently, can cause a patient to bleed to death.
“Fortunately, there are several antidotes to warfarin toxicity – all of which are commonly available to healthcare professionals. Antidotes include injectable vitamin K, plasma, prothrombin complex concentrates, and recombinant factor VIIa.
“One of the big selling points for Pradaxa as opposed to warfarin is that the patient taking Pradaxa does not need regular blood draws or dietary restrictions. What promoters of Pradaxa conveniently do not tell physicians and patients is that there is no commonly available antidote for a Pradaxa overdose. Thus, should a patient’s Pradaxa levels reach a toxic level, he or she has a good chance of bleeding to death while physicians watch helplessly.
“Pradaxa levels are affected by age, kidney function, extremes in body weight, and drug-drug interactions (aspirin, ibuprofen, nonsteroidal antiinflammatory drugs, and many other drugs commonly used by patients). In addition, should a patient on Pradaxa require emergency surgery (as a result of a motor vehicle accident, for example), he or she will be subject to uncontrolled bleeding.
“According to the National Center for Biotechnology Information, ‘In early 2013, there is still no routine coagulation test suitable for monitoring these patients; specific tests are only available in specialized laboratories. In early 2013 there is no antidote for dabigatran, rivaroxaban or apixaban, nor any specific treatment with proven efficacy for severe bleeding linked to these drugs….’
“If your physician has prescribed Pradaxa for you, you should immediately discuss whether there are safer alternative drugs for you. After weighing the risks and benefits, you and your physician can determine what drug is best for you.”
Paul J. M., M.D., J.D.
Attorney at Law, Physician
“I am appalled at the lack of knowledge by physicians on this subject.
“My late husband had atrial fibrillation for which he took warfarin for many years. This was monitored quite closely as he had to have blood taken quite often to check on the bleeding capacity.
“After so many years, Pradaxa came on the market. He wanted to try it so he didn’t have to get ‘stuck’ all of the time. He was told that this drug did not need monitoring, so his doctors did not do it anymore. After a few months of this, he had a stroke – at least that’s what it seemed to be when he went for his morning walk, and died.
“His immune system was compromised, according to one of his doctors. The artery leading to his heart was said to be blocked which never would have happened had he stayed on the Coumadin (warfarin) which was checked every few weeks. “
“I fault the doctors for not checking this more carefully.” G.H.H.