Warfarin has one, but the NOACs don’t. What am I talking about?
Warfarin (Coumadin) has a way to monitor and measure its effectiveness for a specific patient. But there’s no similar way to measure the effectiveness of the new Novel Anticoagulant drugs (NOACs).
Warfarin and Your INR
With warfarin, blood testing for your INR (International Normalized Ratio) will tell your doctor what dosage of warfarin is needed to maintain your ideal INR range between 2.0 and 3.0. (Below 2.0, there’s more of a risk of an ischemic [clotting] stroke; above 4.0, there’s more of a risk of a hemorrhagic [bleeding] stroke.)
NOACs: No Blood Testing but at What Price?
From the clinical trials we know NOACs work as well as warfarin. In addition, the NOACs don’t require periodic blood testing. But the FDA, under pressure for new anticoagulants, approved the NOACs without there being any established or universally recognized method of determining their clot preventing effectiveness.
Without any method of determining their clot preventing effectiveness, how can you determine if your NOAC is working for you? … Continue reading this report…->
Are you taking the blood thinner warfarin to manage your risk of clots and A-Fib stroke? Have you been told to avoid foods with vitamin K to prevent excess clotting? Want to know the facts about warfarin and vitamin K? Take our 5 question quiz to separate the facts from the myths.
A 5 Question Quiz about Warfarin and Vitamin K
1. True or False: Warfarin and vitamin K actually work against each other in your body.
True. Vitamin K helps your blood clot. Warfarin makes your blood clot more slowly. Your INR level is monitored to keep them in balance.
2. True or False: When taking warfarin, you should limit foods with high levels of vitamin K like dark, leafy greens.
False. You don’t need to avoid foods with vitamin K. The key is to consistently maintain your daily level of vitamin K.
Don’t confuse vitamin K with the K on the periodic table for potassium. One’s a vitamin, the other is a mineral.
3. True or False: Vitamin K information is not included on most packaged food nutritional labels.
True. So it’s often hard to determine the amount of vitamin K in your food.
Looking back over 2015, I found five significant developments for those ‘living’ with A-Fib and those seeking their ‘cure’. My ‘Top Five List’ focuses on the Watchman device, a Pradaxa antidote and research findings about lifestyle choices, and reducing fibrosis.
1. FDA Approves the Watchman Device
Anticoagulant Alternative: Because A-Fib patients are at high risk of stroke and clots, a blood thinner (anticoagulant) like warfarin is often prescribed. If you can’t or don’t want to be on blood thinners, you had few options.
That was until March 2015 when the US Food and Drug Administration (FDA) approved the Watchman device. There’s now an option to blood thinners! The Watchman device (Boston Scientific) is inserted to close off the Left Atrial Appendage (LAA), the origin of 90%-95% of A-Fib clots.
To read my complete Top Five List…go to My 2015 Top Five List: A Review of Advancements in the Treatment of A-Fib->.
by Steve S. Ryan, PHD, October 2015, Updated January 26, 2016
According to recent studies, you are better off having a Watchman device installed than spending a lifetime on warfarin.
In two randomized clinical trials comparing Left Atrial Appendage Closure (LACC-Watchman Device) to warfarin, 1,261 patients from the PROTECT AF and PREVAIL trials were studied. The follow-up period was around 3.3 years. Patients receiving the Watchman compared to patients on warfarin had significantly fewer:
• Hemorrhagic strokes
• Cardiovascular/unexplained death
• Non-procedural bleeding
• All-cause stroke or systemic embolism was similar between both strategies.
There were more ischemic strokes in the Watchman device group, but this was balanced by a greater number of hemorrhagic strokes in the Warfarin group.
However, the patients in the control group of the PREVIAL trial were considered “unusual” in that, given their risk profile, they had a much lower ischemic stroke rate than ever observed in any clinical trial. See Getting FDA Approval for the Watchman Device.
What Patients Need to Know: Watchman Actually Better Than Warfarin
The Watchman device provides similar protection against having an A-Fib (ischemic) stroke as being on warfarin.
But the Watchman device isn’t simply an “alternative” to warfarin, but rather an improvement or advance or progression. One would intuitively expect that people receiving the Watchman device would also have less hemorrhagic strokes and bleeding compared to those on warfarin, which these studies do demonstrate.
Welcome Alternative to a Lifetime on Warfarin
Warfarin and other anticoagulants work by causing bleeding and are inherently dangerous. The Watchman device is not only a welcome alternative to a lifetime on warfarin, but is actually better than warfarin.
Long-term use of anticoagulants such as warfarin have been known to not only cause hemorrhagic strokes but also microbleeds in the brain which lead to dementia.
Among other bad side effects, long-term use of anticoagulants such as warfarin have been known to not only cause hemorrhagic strokes but also microbleeds in the brain which lead to dementia. See Patient on Anticoagulation Therapy for 10 Years Develops Microbleeds and Dementia.
A 2015 study found evidence of microbleeds in 99% of subjects aged 65 or older, and that increasing the imaging strength increased the number of detectable microbleeds. Microbleeds have been suggested to be predictive of hemorrhagic stroke.
According to current research, you are better off having a Watchman device installed than spending a lifetime on warfarin. (Of course, this assumes that the doctor performing the procedure is beyond his/her learning curve. That is, when operating doctors are first performing the procedure, there is a higher risk for procedural complications.)
What About the New Anticoagulants (NOACs)?
Does this research apply to the new anticoagulants like Pradaxa, Xarelto, Eliquis and Savaysa/Lixiana? Technically no. This research only applies to warfarin. But intuitively one would expect the same general principles to apply. All anticoagulants cause bleeding. That’s how they work.
Caveat—Long-Term Effects of Watchman?
What are the long-term effects of leaving a mechanical device like the Watchman inside the heart? We know that, after a few months, heart tissue grows over the Watchman device so that the LAA is permanently closed off from the rest of the heart.
It seems unlikely that complications would develop after a long period of time as has happened with warfarin. But we can’t say that for sure until enough time has passed. The first clinical trial installation of the Watchman device in the US was in 2009 and in Europe in 2004. So far no long-term complications have developed.
Preventing Stroke in the Elderly—Even If They Don’t Have A-Fib!
One of the great potentials of the Watchman device is that it may someday be used to prevent stroke in the elderly even if they don’t have A-Fib. Imagine a world where you no longer live in fear of a stroke as you get older, where 90%-95% of stroke risk can be eliminated by a simple 20 minute procedure. The Watchman device (and other Left Atrium Occlusion Devices such as the Lariat and the surgical AtriClip) may change the way elderly medicine is practiced.
How many people turning 70 or 75 would welcome a device that would almost guarantee freedom from the most severe type of ischemic stroke (a cardioembolic stroke)? The Watchman device has the potential to greatly reduce or eliminate the threat of strokes in the elderly!
The blood thinner, warfarin (Coumadin) is a “vitamin K-antagonist” which works by blocking vitamin K thereby affecting several steps in the anticoagulation pathway and decreasing clotting proteins in the blood.
But vitamin K is essential for heart and bone health. Without enough K-2, osteocalcin, a protein that binds calcium to bone, doesn’t function. “When calcium doesn’t stay in bones, it can end up clogging your arteries, causing a heart attack or stroke.” Vitamin K functions to keep calcium out of soft tissues.
In one study, people with the lowest blood levels of vitamin K-2 had a 57% greater risk of dying from heart disease than those with the highest levels. They were also at increased risk for osteoporosis and bone fractures.
Why I Warn Against Taking Warfarin
In a study of 451 women using mammograms to measure arterial calcification, after just one month of warfarin use, arterial calcification increased by 50% compared to untreated women. After five years, arterial calcification increased almost 3-fold.
To avoid arterial calcification, if you are on warfarin (Coumadin), talk to your doctor about switching to Eliquis (apixaban) which tested the best of the NOACs and has the best safety test results. (See my article, Warfarin and the New Anticoagulants.)
Research: Vitamin K Reverses Arterial Calcification from Warfarin
If you have been on warfarin for a while, you will be interested in the evidence that high doses of vitamin K may reverse arterial calcification.
An analysis of kidney failure patients on dialysis found over 50% had vascular calcification (one devastating side effect). A clinical study tested supplementation with vitamin K2 (MK-7) over a six-week period. In the group given 360 mcg of MK-7, the favorable response rate was a remarkable 93%. (When supplementation ceased, these high-risk patients were once again vulnerable to vascular calcification.)
There are three forms of vitamin K: vitamin K1, vitamin K2(MK-4) and vitamin K2(MK-7).
An animal study involved groups of rats who were all initially fed a six-week diet of warfarin to induce calcium buildup in the blood vessels. This was followed by some groups receiving high-dose vitamin K1 or K2 (MK-4).
In six weeks, not only was there no further arterial calcium accumulation, there was a 37% reduction of previously accumulated arterial calcification. After 12 weeks, there was a 53% reduction. The high-dose vitamin K1 and K2 groups also showed a reversal in carotid artery stiffness.
If on Warfarin, You’re Deficient in Vitamin K
According to the U.S. Department of Agriculture (USDA), the recommended range of normal vitamin K intake ranges between 60-80 micrograms for women and 80-120 micrograms for men. (The typical recommended supplement dosage is 90 mcg females, 120 mcg males.)
Nearly everyone is deficient in vitamin K. While most of us may get just enough vitamin K from our diet to maintain adequate blood clotting, most of us should increase our intake of vitamin K through foods like leafy greens, or take vitamin K supplements.
You must always take your vitamin K supplement with fat since vitamin K is fat-soluble and won’t be absorbed without it. Dr. J. Mercola
But if you’re on warfarin, you are NOT getting enough vitamin K to protect you from arterial calcification and a variety of other heart health problems. And certainly not enough to reverse the effects of warfarin on soft tissue calcification.
Counteract Arterial Calcification: What Dosage of Vitamin K?
So the question arises, is there anything we can do to reverse arterial calcification? What amount of vitamin K should you be getting? Sadly, we don’t have enough human research as to the correct dosage, but we do have some indications.
Referring back to the study above with rats, the human equivalent of the vitamin K dose given to the rats is in the range of 52,000 mcg (52mg) to 97,000 MCG) (97mg) per day. Also, in Japan, a 45,000 mcg (45mg) daily dose of the MK-4 form of vitamin K2 is approved as a drug to treat osteoporosis. Admittedly, these are high doses compared to the dietary industry standards.
Consider a high quality MK-7 form of vitamin K2. And as they are inexpensive, include vitamin K1 and MK-4 to help inhibit and possibly reverse vascular calcification.
Although the exact dosage of vitamin K is yet to be determined, one of the world’s top vitamin K researchers, Dr. Cees Vermeer recommends between 45 mcg and 185 mcg daily for adults. (LifeExtension magazine recommends 200 mcg.)
Consider a high quality MK-7 form of vitamin K2. And since vitamin K1 and MK-4 are inexpensive, it makes sense to include them to inhibit and possibly reverse as much arterial calcification as possible. One product to look at is Life Extension Super K with Advanced K2 Complex Softgels, 90-Count available from Amazon.com
Balancing Vitamin K and Warfarin for Proper INR Ratio
People taking warfarin are often told to lower their intake of vitamin K foods like leafy greens, liver, etc., because they interfere with the anti-blood clotting effect of warfarin. Not true.
Prolific A-Fib blogger Dr John Mandrola (Dr. John M.), posted about misinformation surrounding warfarin patients and vitamin K. He wrote:
“I am so utterly tired of correcting this mistake….Patients on warfarin can indeed eat green vegetables; they should just eat them consistently. I have vegetarians who do beautifully on warfarin. The problem comes when people vary the weekly dose of vegetables.
So, if you and your doctor decide that you should take warfarin, take more vitamin K, not less! You can take vitamin K. The key is to be consistent on a daily schedule. If consumption of vitamin K does affect your INR, your doctor can always adjust the warfarin dosage.
Your Bottom Line Goal
If you continue to take warfarin, your goal is to maintain the highest healthy levels of vitamin K to counteract the effects of warfarin on your arterial and bone health.
If you change from warfarin to a NOAC, your goal is to restore your arterial and bone health from the effects of warfarin by maintaining the highest healthy levels of vitamin K.
Stop Taking Warfarin―Produces Arterial Calcification
The blood thinner, warfarin (Coumadin) is a “vitamin K-antagonist” which works by blocking vitamin K (i.e., K-2, menaquinone), thereby affecting several steps in the anticoagulation pathway and decreasing clotting proteins in the blood.
But vitamin K is also essential for heart and bone health. Vitamin K determines whether we maintain strong bone density and soft pliable tissues. Without enough K-2, osteocalcin, a protein that binds calcium to bone, doesn’t function. This vascular calcification produces plaque and reduces aortic and artery elasticity.
“When calcium doesn’t stay in bones, it can end up clogging your arteries, causing a heart attack or stroke.”
Warfarin Blocks Vitamin K: Deposits Calcium in Arteries
By blocking vitamin K (K-2), warfarin deposits calcium in our arteries and progressively turns them into stone. In the absence of vitamin K, bony structures form in soft tissues. When you hear the term “hardening of the arteries,” this means that previously flexible blood vessels are turning into rigid (calcified) bony structures.
In a study of 451 women using mammograms to measure arterial calcification, after just one month of warfarin use, arterial calcification increased by 50% compared to untreated women. After five years, arterial calcification increased almost 3-fold.
Why You Should You Stop Taking Warfarin
If you are taking warfarin (Coumadin), you should talk to your doctor about switching to Eliquis (apixaban) which tested the best of the NOACs and is the safest. (See my article, Warfarin and New Anticoagulants.)
The new oral anticoagulants (NOACs) do not block vitamin K. But the NOACs do have drawbacks. In the case of severe bleeding, there is currently no antidote or reversal agent like there is for warfarin (a reversal agent for the direct factor Xa inhibitors Xarelto and Eliquis is close to FDA approval).
Added 2015: The FDA approved a reversal agent Praxbind for the NOAC Pradaxa Oct. 16, 2015. In clinical trials, 5gs of Praxbind (idarucizumab) administered by IV reversed the anticoagulant effect of Pradaxa within minutes (which is significantly faster than the current antidotes for warfarin).
Whether or not to be on an anticoagulant and which one to take is the most difficult decision you and your doctor have to make (and your initial decision may change over time as your body changes.)
If you aren’t happy with your doctor’s response, get a second opinion. You need to feel confident and at peace with this decision.
Long-term exposure to warfarin and aspirin, if not well controlled, may result in micro bleeds in the brain that accumulate over time raising the risk of dementia, according to Dr. T Jared Bunch of the Intermountain Medical Center, Murray, UT.
Research Findings: Taking Both Warfarin and Aspirin
Speaking at the American Heart Association’s Scientific Sessions 2014, Dr. Bunch described recent research findings on the incidence of dementia in A-Fib patients taking both warfarin (anticoagulant) and aspirin (antiplatelet).
For 10 years, investigators followed 1,031 A-Fib patients with no previous history of stroke or dementia who were taking both warfarin and aspirin (or clopidogrel).
The data focused on A-Fib patients with abnormally slow clotting times, i.e., INR above 3. (These patients were considered to be receiving too much blood thinning medication.)
Patients with frequently elevated INR occurring:
• 25% or more of the time, were more than twice as likely to develop dementia (5.8%).
• 10% –24% of the time, had an incidence of dementia of 4.1%.
• less than 10% of the time had a risk of dementia of 2.7%.
For A-Fib patients taking both warfarin and aspirin, frequent abnormally slow clotting times (an INR score above 3) had a cumulative effect making them more prone to developing dementia.
Previous Research on Warfarin and Dementia
Earlier research found that patients taking warfarin were more likely to develop dementia if their clotting times frequently were too slow or too fast (i.e., an INR above 3 or below 2).
For these A-Fib patients, over-anticoagulation and under-anticoagulation lead to cerebral microbleeds and clots in the brain, important in the development of dementia.
Dr. John Day, a colleague of Dr. Bunch, describes the tragic case of one of his patients who was on warfarin for 10 years and developed cerebral microbleeds and dementia. Read the article.
What The Research Means to A-Fib Patients
According to Dr. Bunch, with warfarin, “it’s very common to have INR outside the ideal range up to 40% of the time, and over the years there may be an accumulative negative impact on cognitive ability.”
Both studies found A-Fib patients on warfarin to be at greater risk of developing dementia. The more recent study found the risk of dementia was greater when taking both warfarin and aspirin, than the risk of dementia when taking warfarin alone.
If you have to take warfarin, don’t start taking aspirin on your own (because you’ve read it’s good for your heart or may reduce cancer risk.) You may be raising your risk of developing dementia.
On Warfarin? How to Reduce the Risk of Dementia
If you are on warfarin because of A-Fib and also have to take aspirin (or clopidogrel) for example because you have a stent, you could be more than twice as likely to develop dementia.
In this case, you probably can’t stop taking aspirin, but there are ways to no longer have to take warfarin.
• A successful catheter ablation for A-Fib reduces your risk of stroke to that of a normal person. (See my post Catheter Ablation Reduces Stroke Risk Even for Higher Risk Patients.)
• You can have your Left Atrial Appendage (LAA) closed off or removed by devices like the Watchman, Lariat II, or surgery with the AtriClip. (Note: 90%-95% of A-Fib clots come from the LAA).
• Consider switching from warfarin to one of the newer anticoagulants such as Eliquis; (But the NOACs are so new, and since they also work by causing bleeding, this strategy may not work. We don’t know if over time they will or will not have similar effects as warfarin.)
Bottom Line: Do Not Routinely Take Both Warfarin and Aspirin
You can no longer afford to routinely take both warfarin (anticoagulant) and aspirin (antiplatelet)! Talk with your doctor about your increased risk of dementia. (Perhaps take along a copy of this post.)
Don’t make changes on your own: Suddenly stopping daily aspirin therapy could have a rebound effect that may trigger a blood clot. If you have been taking daily aspirin therapy and want to stop, it’s important to talk to your doctor before making any changes.
FDA approved in January 2015, the anti-clotting drug edoxaban (brand names Savaysa and Lixiana) is the fourth novel anticoagulant (NOAC) developed as an alternative to the blood thinner warfarin (Coumadin). The others are apixaban (Eliquis), dabigatran (Pradaxa) and rivaroxaban (Xarelto).
Because edoxaban is so new, we don’t have much ‘real world’ data and can only look at the data from the clinical trial. Edoxaban is available by prescription in two dosages: 60 mg once daily and 30 mg once daily.
Prevention of stroke: The higher dose of edoxaban (60 mg once daily) was as good as and tended to be better than warfarin in preventing stroke. But the lower dose (30 mg once daily) wasn’t as effective as warfarin.
Stomach bleeding: All anticoagulants cause bleeding. That’s how they work. With the higher dose of edoxaban, bleeding from the stomach was greater than with warfarin. But with the lower dose of edoxaban, bleeding was lower than with warfarin.
Kidney clearance: Edoxaban is 35% cleared by the kidneys (as compared to 25% for apixaban [Eliquis] and 80% for dabigatran [Pradaxa]). This means if your kidneys are working well (creatine clearance greater than 95ml/min), you probably shouldn’t be taking edoxaban, because your kidneys are taking it out of your body too quickly. This puts you at greater a risk of stroke than those patients taking warfarin.
No Head-To-Head Clinical Tests
Unfortunately, there haven’t been any head-to-head clinical tests comparing edoxaban with the other novel anticoagulants (NOACs). In fact, drug manufacturers have only tested their products against the standard treatment of warfarin (Coumadin).
Safety Data for Edoxaban
Edoxaban is so new we don’t have a real-world safety score yet. But in the clinical trial, stomach bleeding was greater with the higher dose than warfarin. (The lower dose edoxaban is irrelevant because it didn’t work as well as warfarin.)
The Bottom Line for Edoxaban
The limited data about edoxaban in unimpressive. As you know, I’m not a medical doctor. So if you are seeking an alternative to warfarin, talk to your doctor. If I were you, I’d skip edoxaban for now and consider apixaban (Eliquis) instead.
To date, Eliquis is the only novel anticoagulant (NOAC) that can claim that survival improved with its use compared to warfarin. Eliquis was unique in that bleeding from other sites including the stomach, bowels, and bladder was less. Eliquis earned the best safety score from the FDA Adverse Event Reporting System compared to Pradaxa, Xarelto and warfarin. For more, see Warfarin vs. Pradaxa and the Other New Anticoagulants.
by Steve S. Ryan, PhD, Update July 2014, June 2015, October 2015
“I’ve read about people bleeding to death in the ER because they are on the new anticoagulant Pradaxa. Doctors can’t stop the bleeding, even from minor cuts. Is that true? Doesn’t Coumadin carry the same risk? What about the other new anticoagulants Xarelto and Eliquis?”
You’re correct about Pradaxa and the reported bleeding deaths (See “Stop Prescribing or Taking Pradaxa: Suspect in 542 deaths.”) None of the new anticoagulants (including Xarelto and Eliquis) has a proven, reliable antidote or reversal mechanism. But, Pradaxa, in particular, has been associated with tragic deaths in the ER where doctors are helpless and can only watch as someone bleeds to death.
Most would agree that the worst thing that can happen to a patient with A-Fib is a life-altering stroke. A stroke often causes death or permanent disability. Thus the importance of anticoagulation therapy for A-Fib patients.
For many years, there was only one proven therapy for stroke prevention in A-Fib patients at high or intermediate risk for stroke: the anticoagulant Coumadin (warfarin). It’s readily available and inexpensive.
But maintaining correct Coumadin levels is difficult especially over the long haul (studies indicate around 30% of people will stop taking Coumadin).
But maintaining correct Coumadin levels is difficult especially over the long haul (studies indicate around 30% of people will stop taking it).
In addition, Coumadin taken over several years may lead in microbleeds in the brain and dementia. (Read about the post-ablation patient on anticoagulation therapy for 10 years who develops cerebral microbleeds and early dementia: The New CHA2DS2-VASc Guidelines and the Risks of Life-Long Anticoagulation Therapy )
For patients at low or intermediate risk of stroke (including younger patients without any additional stroke risk factors) aspirin may be prescribed, or no anticoagulation therapy at all.
Read about the post-ablation patient on anticoagulation therapy for 10 years who develops cerebral microbleeds and early dementia: The New CHA2DS2-VASc Guidelines and the Risks of Life-Long Anticoagulation Therapy
The NOACs Trials
For over 20 years there have been extensive efforts to replace warfarin with other drugs. In the US, we have four new anticoagulants to consider: Pradaxa (dabigatran), Xarelto (rivaroxaban), Eliquis (apixaban), (added January, 2015) and the recently approved (January, 2015) Savaysa (edoxaban)).
The data on the new anticoagulant come from three randomized controlled trials involving more than 50,000 A-Fib patients:
Each study compared one drug against warfarin (not against each other). Taken together, these studies consistently revealed that A-Fib patients who took the non-warfarin blood thinners suffered fewer strokes, intracranial bleeds, and serious bleeds than those who took warfarin.
All of these drugs are at least as good as warfarin for preventing stroke and all are better than warfarin in reducing your risk of serious bleeding in the brain. But none have antidotes or reversal agents (at this time).
Note: Each of these NOAC trials had a questionable bias toward the new drug when compared against warfarin. Warfarin users are notoriously non-compliant, up to 50% are inconsistent in managing their diet, monitoring their INR levels and taking the correct dosage.4 Each of the three trials compared a group of compliant patients against a group of inconsistent warfarin patients. So results should be viewed with a critical eye.
For a more in-depth look at the clinical trials of the new NOACs, see 2013 BAFS: The New Anticoagulants (NOACs).
Three Notable Concerns
The new anticoagulants offer several advantages over warfarin. They are fast acting. And when stopped (i.e., for surgery), they just as quickly clear your body (a short “half-life). There’s a broad therapeutic window (wide range of safe use), and they have minimal drug or dietary interactions. They can be administered in fixed doses without monitoring, making them potentially more convenient to use than warfarin.
Remember: The goal of anticoagulation therapy is to reduce your risk of life-altering stroke.
Enthusiasm for the new anticoagulants, (NOACs), however, must be tempered by three notable concerns in patients taking these drugs:
1. No readily available means for assessing the degree of anticoagulation
2. No readily available reversal strategy
3. Life-threatening bleeding complications can occur after an injury
(Added May, 2015) Dr. Stephen Kimmel of the Un. of Pennsylvania discusses a fourth concern—stomach problems and gastrointestinal bleeding. “If you have a history of stomach problems or gastrointestinal bleeding, you may want to avoid Pradaxa and Xarelto—both medications have the highest risk for those complications.”5
No Way to Measure Effectiveness
One of the problems with the newer anticoagulants (NOACs) is we don’t have a good way to measure how effective they are or how much of an anti-clotting effect there is at a given point in time. (For example, in treating trauma patients, ER doctors can only use the elapsed time from the last dose to estimate the clotting effect.)
With Coumadin (warfarin), on the other hand, we can measure how effective it is by its level in the blood stream measured in INR (International Normalized Ratio). A person not on anticoagulants will have an INR slightly above 1 (the author’s INR is 1.1). Someone with A-Fib on Coumadin should have an INR between 2.0 and 3.0. At this INR level a person will bleed more than someone with an INR of 1.0, but the blood will still clot.
With an INR below 2.0 you are more in danger of having an ischemic (clotting) stroke, the kind that most often occurs in A-Fib. With an INR of 4.0 and above, there is much more risk of blood not clotting and of developing a hemorrhagic stroke.
But the INR blood test doesn’t work with the new anticoagulants which affects only one particular stage in the anticoagulation process. Pradaxa, for example, is a direct thrombin inhibitor, whereas Coumadin affects nearly every stage in the anticoagulation process. (Thrombin is an enzyme that converts soluble fibrinogen into insoluble fibrin. Fibrin is a fibrous protein involved in the clotting of blood. It forms a mesh or clot over a wound.)
The lack of a readily available method to determine the degree or current level of anticoagulation is a major challenge for ER physicians and staff treating trauma patients.
Are the NOACs Too Effective?
Pradaxa, in particular seems to work almost too well.
Pradaxa, in particular seems to work almost too well.
Coumadin on the other hand has several proven, time-tested reversal or antidote strategies.6
Pradaxa (dabigatran) won the FDA sweepstakes by being the first new anticoagulant to get FDA approval and consequently captured a significant share of the anticoagulant market. Pradaxa comes in two doses in the United States, 150 mg twice daily or 75 mg twice daily. It’s large and harder to swallow, comes in a bottle with a 30-day shelf life once opened (or in blister packs which eliminates the shelf-life problem.) And it’s expensive.7 In the RELY trial, Pradaxa was not only equal to warfarin, but it proved to be superior to it in preventing stroke. Bleeding rates in the head were lower with Coumadin. However, bleeding from the stomach or bowels was higher. The most common side effect was stomach pain.
In addition to the bleeding deaths in the ER mentioned above, Pradaxa’s own fact sheet states common side effects of Pradaxa include:8
• Indigestion, Upset Stomach, or Burning
• Stomach Pain
[These statements don’t capture the actual human toll—burning throat, roiling intestines, diarrhea, burning anus, lasting intestinal damage, etc. that Pradaxa can produce in some people.]
Xarelto and Eliquis Test Better
Xarelto (rivaroxaban) was the second drug available in the United States. Xarelto comes in two doses, 20 mg daily or 15 mg daily. In contrast to Pradaxa, it is a small pill taken once-a-day that doesn’t seem to cause a lot of intestinal problems. In the Rocket AF trial, Xarelto also significantly lowered the risk of bleeding in the brain and head compared to Coumadin. Like the other new anticoagulants, Xarelto also doesn’t have a reversal agent; but anecdotally we don’t seem to see a lot of deaths in the ER from Xarelto.
Eliquis (apixaban) was third to be approved, comes in two doses, 5 mg twice daily or 2.5 mg twice daily (the lower for A-Fib patients with kidney dysfunction). Similar to Xarelto, the risk of bleeding in the brain and head was lower versus Coumadin. However, this drug was unique in that bleeding from other sites including the stomach, bowels, and bladder was less. In the Aristotle trial, Eliquis was at least as good and tended to be better than warfarin at preventing stroke. Eliquis is the only drug that can claim that survival improved with its use compared to warfarin.
Xarelto and Eliquis, just like Pradaxa, are also very expensive.
The reported bleeding events tend to occur mainly in elderly patients (median age of 80) which raises a question regarding safe dosing and monitoring in older patients. Elderly patients often have mild to moderate renal impairment, which can cause plasma levels of the NOAC to increase to up to three times those in normal renal function.
“One-size-fits-all” dosage of these new anticoagulants may need to be re-examined for elderly patients. (The FDA rejected the lower 110-mg twice-daily dose of Pradaxa (dabigatran) tested in the RE-LY trial, instead approving a 75-mg twice-daily dose just for patients with severe renal impairment.)
Lack of a proven, reliable antidote or reversal mechanism creates a major challenge for trauma staff.
With a relatively short elimination half-life, for now, time may be the most important antidote for NOACs.
Eliquis Earns Best Safety Score
Through an analysis of data from the FDA Adverse Event Reporting System by AdverseEvents, Inc., Eliquis has received an “RxScore” safety score of 39.45 on a 100 point scale, with 100 representing the highest risk. In comparison, warfarin had a score of 67.57. Pradaxa (dabigatran) had a score of 67.15, Xarelto (rivaroxaban) 67.08.9,10
The FDA’s database comprises all the reports made by doctors, patients and other healthcare providers, which means it’s not a “scientific” finding with the authority of a clinical trial. AdverseEvents applies logic, math and software to the database to sift out the important data.
For Eliquis, “the rate of suspect cases was lower in every type of adverse-event report, from hospitalization to death.” For example, among Eliquis patients reporting side effects, only 21% cited hospitalization, while Pradaxa had 39%, Xarelto 43% and warfarin 50%.
The results all point to the same general conclusion: Eliquis may be a safer choice among the new NOACs.
Update May 2014: Pradaxa
Since it was approved for use in 2010, Pradaxa has been linked to more than 500 patient deaths. More than 1,600 individuals have filed lawsuits in state and federal courts in the United States alleging they suffered bleeding events caused by the drug.
In May 2014, Boehringer-Ingelheim, the privately held German company that makes Pradaxa, settled 4,000 Pradaxa lawsuits and will pay $650 million. The lawsuit states that Pradaxa can cause bleeding events that cannot be controlled and are sometimes fatal.11
Pradaxa has generated $1 Billion in revenue for Boehringer-Ingelheim. So, will this $650 million settlement hurt BI’s bottom line and affect its marketing of Pradaxa? (BI’s revenues in 2012 were $1.5 billion). Probably not.
If you’re conscientious and are pretty good at staying in the proper INR range, stick with Coumadin if you can. It may not be as convenient and easy to use as the newer anticoagulants, but we know Coumadin works if you stay within the proper INR range. And there are proven reversal agents for Coumadin, unlike for the newer anticoagulants. The cost of Coumadin is significantly lower when compared to the new anticoagulants.12
Update June 2015: Instead of the above statement, I suggest you talk with your doctor about switching from warfarin (Coumadin) to the NOAC Eliquis (apixaban). Studies show that warfarin produces arterial calcification and plaque which damage your heart over time. (See Stop Taking Warfarin! Switch to Eliquis.) Eliquis doesn’t block Vitamin K like warfarin, it tested better than the other NOACs and is safer.
If you struggle with staying in the proper INR range13, can’t juggle the diet restrictions or monthly monitoring, you should talk with your doctor about switching to Eliquis. It has no interactions with food (not even spinach) and requires NO monitoring (no more finger stick checks). Though be aware of Eliquis’ much higher monthly price.14 You will need to judge if the benefits outweigh the costs.
When choosing an anticoagulant, you need to consider which is worse: the risk of uncontrolled bleeding or the risk of a debilitating stroke.
Update October 26, 2015: FDA Approves Reversal Agent for Pradaxa (dabigatran)
In a new study of 90 patients who had uncontrolled bleeding with Pradaxa, Praxbind (idarucizumad) stopped this bleeding within minutes. No serious side effects were reported.
We have previously reported on the reversal agent Andexanet Alfa which is on FDA fast track approval as an antidote to the Factor Xa inhibitors Xarelto and Eliquis. FDA approval is pending.15,16
Last updated: Saturday, March 26, 2016
- Connolly SJ, et al. RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. Last accessed July 10, 2014 URL: http://www.ncbi.nlm.nih.gov/pubmed/19717844↵
- Patel MR, et al. ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-91. Last accessed July 10, 2014, http://www.ncbi.nlm.nih.gov/pubmed/2183095↵
- Granger CB, et al. ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011; 365(11):981-92 Last accessed July 10, 2014↵
- Ansell J, et al. Descriptive analysis of the process and quality of oral anticoagulation management in real-life practice in patients with chronic non-valvular atrial fibrillation: the interactional study of anticoagulation management (ISAM) J Thromb Thrombolysis 2007; 23: 83—91. Last accessed July 10, 2014↵
- Kimmel, Stephen. The Truth About Blood Thinners, Bottom Line/Health, May 2015, p. 11↵
- Coumadin reversal or antidote strategies: Vitamin K antagonist, Fresh Frozen Plasma, Prothrombin Complex Concentrate (PCC), and the newly FDA-approved Kcentra.↵
- Pradaxa costs about $250 a month; By comparison, warfarin (Coumadin) costs about $60-$80/month when you add in INR monitoring once a month. Last accessed July 10, 2014↵
- Pradaxa: Highlights of Prescribing Information. Boehringer-Ingelheim website. Last accessed March 13, 2014 URL: http://tinyurl.com/PraxadaInfo↵
- Examining the Comparative Safety of Blood Thinners: An Analysis Utilizing AdverseEvents Explorer, February 2014, Special Report Download. http://info.adverseevents.com/special-report-blood-thinner Last accessed July 10, 2014↵
- Staton, Tracy. Eliquis earns best safety score in its class in analysis of FDA adverse event reports. FiercePharma, February 26, 2014. Last accessed July 10, 2014, http://www.fiercepharma.com/story/eliquis-earns-best-safety-score-its-class-analysis-fda-adverse-event-report/2014-02-26↵
- Feeley, Jef. Boehringer Pays $650 Million to End Blood-Thinner Cases. May 28, 2014. Bloomberg.com. Last accessed July 10, 2014, URL: http://www.bloomberg.com/news/2014-05-28/boehringer-pays-650-million-to-end-blood-thinner-cases.html↵
- Your insurance provider will have a direct say into which drug you take.↵
- Consider a warfarin sensitivity test. About a third of the people who take warfarin are at a higher risk of bleeding because their genes make them more sensitive to warfarin. If a family member experienced side effects, talk to your doctor about taking a genetic warfarin sensitivity test.↵
- For those in the US and on Medicare with Part D coverage, the monthly cost may range from $30 to $50.↵
- Marzo, Kevin. Blood thinner Antidote. Bottom Line Health, Volume 29, Number 9, September 2015, p. 1.↵
- Mundell, E.J.. Drug May Be Antidote to Bleeding Tied to Blood Thinner Pradaxa. Medline Plus. Monday, June 22, 2015. http://www.nlm.nih.gov/medlineplus/news/fullstory_153206.html↵
Jeff Patten’s A-Fib started briefly in 2000, then returned in 2010 when his father-in-law died. The emotional upset, high summer heat, stress and accumulated age, followed closely by a bout with appendicitis, put him back into A-Fib .
In 2012, came a successful CryoBalloon ablation. But Jeff’s post-ablation recovery on Pradaxa turned into “alimentary torture” and burning diarrhea. Later came a Right Atrium Catheter Ablation for PACs/PVCs. Learn how Jeff emerged in 2015 healthy and A-Fib free.
Atrial Fibrillation patients often search for unbiased information and guidance about medicines and drug therapy treatments. These are answers to the most frequently asked questions by patients and their families. (Click on the question to jump to the answer.)
11. “I am on Coumadin (warfarin) to thin my blood and prevent A-Fib blood clots. Do I now need to avoid foods with Vitamin K which would interfere with the blood thinning effects of Coumadin?” UPDATED
12. “The A-Fib.com web site claims that an A-Fib stroke is often worse than other causes of stroke. Why is that? If a clot causes a stroke, what difference does it make if it comes from A-Fib or other causes? Isn’t the damage the same?“
16. “I have to be on aspirin for stroke prevention. Which is better—the low-dose baby aspirin (81 mg) or a high dose (325 mg)? Should I take the immediate-release (uncoated) or the enteric-coated aspirin?”
17. “I don’t want to be on blood thinners for the rest of my life. I’ve had a successful catheter ablation and am no longer in A-Fib. But my doctor says I need to be on a blood thinner. I’ve been told that, even after a successful catheter ablation, I could still have “silent” A-Fib—A-Fib episodes that I’m not aware of. Is there anything I can do to get off of blood thinners?“
21. “I”ve read about a new anticoagulant, edoxaban, as an alternative to warfarin (Coumadin) for reducing risk of stroke. For A-Fib patients, how does it compare to warfarin? Should I consider edoxaban instead of the other NOACs?”
Last updated: Wednesday, May 25, 2016
13. “After my cardioversion, my doctor kept me on Coumadin for a month. Why is that required? They mentioned something about a “stunned atrium. What is that?”
A “stunned atrium” is medically defined as a “state of temporary mechanical atrial dysfunction with preserved bioelectrical function.” In non-medical terms your heart doesn’t contract properly even though it is getting the right electrical and chemical signals to contract.
This can happen after an electrical cardioversion and is why the left atrium and, in particular, the Left Atrial Appendage tend to develop clots after an electrical cardioversion. The left atrium, and especially the Left Atrial Appendage, is “stunned” after the electrical shock and may not contract and pump out properly.
Clots can develop and be released when the LAA starts to contract again. That’s why you need to be on a blood thinner like Coumadin (generic name: warfarin) for a month after your electrical cardioversion.
Thanks to David Mobley for this question.
Dabek, J. et al. Cardioversion and atrial stunning. Pol Merkur Lekarski. 2007 Mar;22(129):224-8. PMID: 17682682 (PubMed – indexed for MEDLINE)
Grimm RA et al. Impact of electrical cardioversion for atrial fibrillation on left atrial appendage function and spontaneous echo contrast: characterization by simultaneous transesophageal echocardiography. J Am Coll Cardiol. 1993 Nov 1;22(5):1359-66. PMID 8227792
Return to FAQ Drug Therapies
10. “I’m worried about the risk of bleeding. I have to take the blood thinner warfarin ( Coumadin). If I cut myself, do I risk bleeding to death?”
In general, no.
On a normal dosage of warfarin (Coumadin) you will bleed longer if you cut yourself (minor wound). But your blood will still clot.
You will also bruise more easily. You should stay away from contact sports like hockey, football, rugby, etc. or activities where you could easily injure yourself like mountain climbing, competitive biking, etc. (Professional athletes should not be on warfarin). But you can do normal daily activities on warfarin.
However, you may want to get a Medical ID Alert wallet card, bracelet or dog tag. Then, in case of an emergency, paramedics and doctors will know you’re taking a blood thinner.
If you do have a more serious injury, you are definitely more at risk to bleed to death than if you weren’t on warfarin.
If you’re taken to an Emergency Room for treatment, most ER personnel are experienced in using proven antidotes to reverse the blood thinning effects of warfarin. But depending on the seriousness of your injury, there’s no guarantee the reversal agents for warfarin will work in time.
(The newer anticoagulants like Pradaxa, Xarelto, Elquis unfortunately have no proven antidote. Pradaxa in particular seems to be associated with many deaths in the ER where doctors currently have no way to stop people from bleeding to death. See my article, Stop Prescribing or Taking Pradaxa)
Return to FAQ Drug Therapies
8. “I’m on warfarin. Can I also take aspirin, since it works differently than warfarin? Wouldn’t that give me more protection from an A-Fib (ischemic) stroke?”
No, combining is dangerous.
Preliminary research indicates that combining anticoagulants (warfarin) and antiplatelets (aspirin) in the same patient is associated with a substantially higher risk of fatal or non-fatal internal bleeding.
There’s no indication that combining warfarin with an antiplatelet (aspirin, clopidogrel, or both) reduces the risk of ischemic stroke.
Added 8/10/15. Aspirin is no longer recommended as first-line therapy:
Aspirin has been downgraded from class 1 in the 2006 guidelines to class 2B in the 2014 guidelines.
In a Danish registry study, aspirin didn’t show any benefit for stroke prevention.1 And in the European ESC guidelines, aspirin is not recommended as first-line therapy for patients with a CHA2DS2-VASc score of 1.2
Return to FAQ Drug Therapies
- Olesen, JB et al. Risks of thromboembolism and bleeding with thromboporphylaxis in patients with atrial fibrillation: a net clinical benefit analysis using a ‘real world’ nationwide cohort study. Thromb Haemost 2011;106:739-749↵
- Camm, AJ et al. 2012 focused update of the ESC Guidelines for the management of atrial fibrillation: an update of the 2010 ESC Guidelines for the management of atrial fibrillation. Developed with the special contribution of the European Heart Rhythm Association. EUR Heart J 2012;33:2719-47↵
7. “What’s the difference between warfarin and Coumadin?”
“Warfarin” is the name of the generic medication, whereas “Coumadin” is the brand name. In general, generic medications are very similar to the brand name medications.
There is anecdotal testimony that Coumadin may be more effective than warfarin. It’s up to you and your doctor to determine which is better for you.
Return to FAQ Drug Therapies
6. “Which is the better anticoagulant to prevent stroke in atrial fibrillation patients—aspirin or warfarin (Coumadin)?”
See August 2015 update below.
People with less risk factors for stroke are sometimes put on aspirin. People more at risk for stroke such as those over 65 years old with frequent A-Fib episodes are often on warfarin (Coumadin) (baring other risk factors such as peptic ulcer, etc.).
Aspirin and warfarin work differently.
Aspirin is an antiplatelet drug that decreases the stickiness of circulating platelets (small blood cells that start the normal clotting process), so that they adhere to each other less and are less likely to form blood clots.
Whereas warfarin (brand name Coumadin) is an anticoagulant that works by slowing the production of blood clotting proteins made in the liver.
Current research indicates that aspirin is not as effective in preventing blood clots (and therefore, strokes) as Coumadin.
Younger people with a low risk of an A-Fib stroke “appear to derive little benefit from warfarin. And, indeed, warfarin may do more harm (intracranial hemorrhage) than good (prevention of ischemic A-Fib stroke).”
Bottom line: Weighing the various risk/benefit ratios is a decision for you and your doctor and may change as you grow older.
August 2015 Update: Aspirin is No Longer Recommended as First-Line Therapy for A-Fib
Aspirin is no longer recommended as first-line therapy for Atrial Fibrillation patients according to the 2014 AHA/ACC/HRS Treatment Guidelines for Atrial Fibrillation. Though not a new finding, it should be noted that aspirin has been downgraded to a class 2B drug.
A similar directive is included in the 2012 European ESC guidelines for the Management of Atrial Fibrillation: aspirin is not recommended as first-line therapy for patients with a CHA2DS2-VASc score of 1.
Aspirin is not appropriate for people who are at low risk of cardiovascular disease and stroke. For these people, the risks of gastrointestinal bleeding and hemorrhagic strokes outweigh any potential benefit. “Among the more than 16,000 deaths each year linked to bleeding…,about one-third of those deaths occur in those who take low-dose (81-mg) aspirin.” The FDA in 2014 warned against widespread use of aspirin in people of average risk.
Aspirin also causes stomach ulcers in 13% of those using it. And these ulcers usually develop without any warning symptoms. Many of these ulcers will cause a serious stomach bleed at some point. Also, taking low-dose aspirin on a regular basis more than doubles your risk of developing wet macular degeneration. On the positive side, people regularly taking low-dose aspirin have a significantly lower chance of getting cancer. But according to Dr. Randall S. Stafford of Stanford, “no one should take daily, low-dose aspirin solely for the purpose of preventing cancer.”
When is aspirin appropriate? Aspirin is recommended for “secondary” prevention of cardiovascular disease such as to prevent reoccurrence of a stroke or heart attack. Aspirin significantly reduces the risk for a second heart attack or stroke.
Return to FAQ Drug Therapies
Last updated: Thursday, September 24, 2015
5. “Should everyone who has A-Fib be on a blood thinner like warfarin (Coumadin)?”
Not necessarily. The biggest danger of A-Fib is the increased risk of stroke, because your heart isn’t pumping out properly.
A blood thinner is used to help protect you from stroke. Your doctor will evaluate your risk of an A-Fib related stroke. If you are young, athletic and in overall good health, your doctor may rate your risk of stroke as low and not put you on a blood thinner.
See, also, the FAQ question “Which is the better anticoagulant to prevent stroke?”
Return to FAQ Drug Therapies
By Steve S. Ryan, PhD, updated March 2015
Do you hate having to take Coumadin or other blood thinners? Hate the side effects? Or are you allergic to them? A replacement to taking blood thinners is the Watchman, an occlusion device.
The theory behind the WATCHMAN™ LAA closure technology is that most A-Fib clots originate in the Left Atrial Appendage (LAA). The Watchman closes off the LAA where 90-95% of A-Fib strokes come from. It’s a very low risk procedure that takes as little as 20 minutes to install. Afterward, you would usually not need to be on blood thinners.
How It Works
The Watchman device comes in multiple sizes from 21mm to 33mm to accommodate the different sizes of LAAs. Once a patient’s Left Atrial Appendage is measured, a wide-sheathed catheter with a spline is used to insert the Watchman device which has a self-expanding Nitinol (a special metal) open-ended circular frame.
The atrial surface of this frame is covered with a thin, permeable 160 μm (micron) pore filter made of polyester material (Polyethylene Terephthalate known as Dacron or PET). This filter allows blood to pass through while stopping clots. Little hooks or anchors called fixation barbs at the middle of the device make sure it is attached firmly to the LAA wall.
Before the catheter is removed (which fixes the Watchman in place), contrast agents are used to make sure the Watchman is stable and entirely closes off the LAA opening. Over time heart tissue grows over the polyester (PET) material so that it completely closes off the LAA with smooth heart tissue similar to other heart surfaces.
In this Occlusion image, heart tissue has completely covered the Watchman device after only nine months.
Patients on Coumadin continue to take it for six weeks after the Watchman device is inserted. They are then examined using a TEE (Transesophageal Echocardiogram) to make sure there is complete closure of the LAA. At that time they are taken off of Coumadin and put on a different type of blood thinner called clopidogrel (Plavix) until six months after the implant procedure.
Think of the Watchman as a replacement for blood thinners; both reduce but do not totally eliminate the risk of stroke. The stroke risk is reduced to that of a person with a normal heart.
Even while you are waiting for or trying to decide on having a Pulmonary Vein Ablation, you can have the Watchman inserted and reduce your stroke risk to that of a person without A-Fib.
Just as closing off the LAA is standard practice in the Cox Maze/Mini-Maze operations, in the future, the Watchman device could become part of most catheter ablation procedures. If included with the ablation procedure, the Watchman would protect the patient from blood clots even if the catheter ablation procedure was unsuccessful. The Watchman device may become standard therapy for anyone at risk of a stroke, not just for people with A-Fib.
For a list of US doctors installing the Watchman device, go to Steve’s Lists/Doctors Installing the Watchman Device.
Update: The U.S. Food and Drug Administration (FDA) approved Boston Scientific’s WATCHMAN™ LAA closure technology for use in the U.S. on March 13, 2015. It has been available internationally since 2009. The FDA approval of the WATCHMAN device is based on the clinical program which consists of numerous studies, with more than 2,400 patients and nearly 6,000 patient-years of follow-up. The Watchman device will be available first at U.S. centers where it has been used in clinical studies.
ATRIA Findings: Anticoagulants for Stroke Prevention Versus Risk of Intracranial Hemorrhage
Anticoagulants are prescribed for Atrial Fibrillation patients to reduce the risk of clots and stroke. But anticoagulants can also increase the risk of intracranial hemorrhage. So, who benefits and who may be harmed?
The “AnTicoagulation and Risk Factors in Atrial Fibrillation” Study (ATRIA) has contributed significantly to better understanding which A-Fib patients will benefit most from anticoagulant therapy.
A-Fib and Stroke Risk
As a consequence of atrial fibrillation, the pooling of blood in the atrial chambers of the heart significantly increases the risk of formation of blood clots. If a piece of a blood clot breaks off and travels to the brain it can occlude (block) a blood vessel and prevent blood from reaching the affected area of the brain. This condition is known as an ischemic stroke and can cause severe disability including the inability to walk or talk.
Ischemic Stroke Versus Intracranial Hemorrhage
In order to reduce the risk of ischemic stroke in people with atrial fibrillation, anticoagulant (blood thinner) medications are often prescribed. The most commonly used blood thinner is warfarin (Coumadin) although aspirin may also sometimes be used. While blood thinners can prevent ischemic stroke in people with atrial fibrillation, paradoxically, they can also cause bleeding into the brain, a condition known as intracranial hemorrhage.
Unfortunately, doctors don’t have a fool-proof method of determining which patients with atrial fibrillation will benefit from blood thinners (prevention of ischemic stroke) and which patients may be harmed by blood thinners (cause an intracranial hemorrhage).
Clearly, more research is necessary to more accurately identify those patients who would benefit the most from taking blood thinners as opposed to those who are more likely to be harmed by taking blood thinners.
The “AnTicoagulation and Risk Factors in Atrial Fibrillation” Study (ATRIA)
The “AnTicoagulation and Risk Factors in Atrial Fibrillation” Study (ATRIA) published in 2009, by a collaborative group of researchers from the Massachusetts General Hospital, the University of California at San Francisco, and Kaiser Permanente of Northern California, has contributed significantly to better understanding which patients with atrial fibrillation would benefit most from receiving anticoagulants for stroke prevention.
The study population consisted of 13,559 people with atrial fibrillation with a median age of 73 years. Twenty (20) percent of the subjects had no major risk factors for ischemic stroke. The major risk factors for ischemic stroke include older age (75 years or older), previous history of stroke, diabetes, hypertension, and congestive heart failure. This stroke-risk classification system is known as the CHADS2 grading system and is used by doctors as a basis for classifying patients with atrial fibrillation into stroke risk categories (low, intermediate, or high).
The researchers followed the clinical course of these 13,559 patients for a median of 6 years. At the time of enrollment into the study, 53% of the subjects were receiving warfarin (Coumadin) as prophylaxis for stroke prevention. During the follow-up period, the researchers identified a total of 1,092 thromboembolic events (occlusion of a blood vessel by a blood clot) among the study subjects, the overwhelming majority of which (1,017 cases or 93%) were ischemic strokes. Of the patients who experienced a thromboembolic event, 37% were receiving warfarin and 63% were not receiving warfarin.
The researchers also identified 299 patients among the study cohort who experienced an intracranial hemorrhage, of which 193 patients (65%) were receiving warfarin.
ATRIA Study Key Findings
The major findings of the study can be summarized as follows:
• The greatest benefit of anticoagulation therapy for the prevention of ischemic stroke was observed among patients with a history of ischemic stroke and those in the highest stroke risk category as determined by the CHADS2 stroke-risk grading system.
• In general, the net benefit of receiving warfarin anticoagulation therapy increased with advancing age. Patients with atrial fibrillation in the oldest age group (85 years of age or older) derived more benefit from warfarin prophylaxis than patients in the 75 to 84 year age group, although the benefits of warfarin prophylaxis was apparent in this age group as well.
• This finding strongly suggests that elderly people with atrial fibrillation who are not taking warfarin are at increased risk for ischemic stroke, however, adding warfarin for prevention of ischemic stroke in elderly people does not significantly increase the risk of intracranial hemorrhage.
• Younger people with atrial fibrillation (64 years or younger) who are considered at low risk for developing an ischemic stoke as measured by the CHADS2 stroke-risk grading system, appear to derive little benefit from warfarin prophylaxis and, indeed, adding warfarin may do more harm (intracranial hemorrhage) than good (prevention of ischemic stroke).
Who Will Benefit, Who May Be Harmed
In summary, this study has contributed significantly to more clearly identifying which patients with atrial fibrillation will derive the most benefit from warfarin anticoagulation therapy and which patients may be harmed by this treatment.
If you have atrial fibrillation, talk to your doctor about the risks and benefits of taking blood thinner medications. In general, older people and those at highest risk for ischemic stroke as determined by the CHADS2 stroke-risk grading system will gain the most from anticoagulation therapy.
Blood thinners, however, may not be advantageous and may cause more harm than good in younger patients with atrial fibrillation who are considered to be at low risk for developing an ischemic stroke.
Last updated: Sunday, February 15, 2015