2017 update on the changing use of “blood thinners” for AF

Times have changed in the treatment of patients with atrial fibrillation (AF).

First some background: The first of the four pillars of AF care is stroke prevention. The only proven means to protect patients with AF from stroke is use of drugs that block clotting factors–or anticoagulants.

Some people call these drugs blood thinners. I don’t. That’s because they don’t thin the blood. They inhibit proteins in the blood that form clots; viscosity of the blood is not affected. Blockade of clotting factors works because static blood in the fibrillating (non-contractile) atria increases the probability of clots, which can break off, travel north and cause stroke.

A study just published in the Journal of the American College of Cardiology reported changing patterns in the use of clot-blocking drugs. It was a registry study in which doctors across the world entered patients with AF into a data bank. Then researchers tallied up the number of patients who took the drugs and which type of drugs were used.

The major finding of the study is something I see happening in my practice: the choice of clot-blocking drugs is moving strongly away from warfarin (Coumadin) and towards the new oral anticoagulant drugs (NOAC), such as dabigatran (Pradaxa), rivaroxaban (Xarelto) and apixaban (Eliquis).

In the registry study, prescriptions for NOAC drugs outnumbered warfarin–48% to 32%.

Since this comes up so often, I will offer three reasons for this trend.

First is that the NOAC drugs are easy to use. The NOAC effect on clotting is immediate. With warfarin, the effect on clotting is delayed. And the convenience continues past the initiation phase. NOAC drugs don’t require frequent testing; they don’t require attention to dietary patterns and they have fewer interactions with other drugs.

I see convenience as important because less time spent being a patient is more time spent enjoying normal life. Convenience also means patients are more apt to take the drugs. Studies show adherence to NOACs is greater than warfarin.

The second reason for increased use of NOAC drugs is that they provide reliable effects. This is important–and the issue comes up all the time in questions from patients: “Doc, how do you know how thin my blood is? With warfarin, you measure the effect but with these new drugs, you don’t?”

The answer is that NOAC drugs have predictable metabolism. That means when I take 20 mg of rivaroxaban it produces the same blood levels of the drug that it would in you. This is not the case with warfarin. Warfarin is broken down by liver enzymes that vary in strength from person to person. My dose of warfarin might be 1 mg daily and yours might be 10 mg daily. Most drugs are like NOACs. Oral antibiotics, for instance, are dosed by standard milligrams. So are ulcer drugs and even aspirin.

The third reason NOAC drugs are taking off is that we aren’t seeing a lot of problems. This brings up another FAQ: “Doc, what are the side effects of NOAC drugs?”

My answer here is almost none. Patients tolerate the drugs well. Dabigatran can cause a bit of reflux and stomach burning–but this side effect simply requires changing to another agent.

Notice I did not list bleeding as a side effect. Bleeding is part of the stroke-prevention equation; it’s almost an effect rather than a side effect.

When you take a clot-blocking drug, you are making a gamble. You take the drug because numerous studies show that they reduce the probability of a future stroke. That’s good. But the drugs also increase the odds of having a bleed. That’s bad. Note this all about probability.

Doctors like this trade in most cases because strokes are worse than bleeds. I tell patients that strokes can cause permanent disability–or said another way, strokes can steal part of what makes us human. Things like thinking, speech, movement, swallowing, etc. Bleeds, on the other hand, are scary and dangerous, but most patients leave the hospital with their human functions intact.

The problem is that doctors don’t ever see patients for strokes prevented. These patients don’t come to the emergency room or our office and say–“look, I didn’t have a stroke.

We only see the bad outcomes. You also may know someone who had a bleeding outcome with a clot-blocking drug.

It’s important to recognize this as availability bias. A bad case of bleeding can trick our brains into ignoring the actual statistics.

JMM

29 comments

  1. Dr. John:

    I’m not usually a big fan of your writing but this article is actually pretty good. While these NOACs are great advancements in medicine, I’m even more hopeful with devices such as the Watchman Device.

    As an afib patient myself, I’ll take a “mechanical” fix over a chemical fix all day long. I’m not in a situation where I need to take daily NOACs but if it ever comes to that, I’ll be skipping them all together and going straight for the Watchman.

    These NOACs may be relatively safe but I’ll do whatever it takes to avoid taking drugs the rest of my life.

    Travis

    1. Travis – I have read a good swath of what is written about AFIB since being diagnosed a few years back. I find Dr M’s clear, open minded and empathic writing to be a bright spot in a rapidly developing field of medicine that suffers from way too much dogma. Why on earth would you take exception to this? Not trying flame you, but it seems off base. Is it the style or the message that you take exception to?

      Joe

  2. I am a great fan of your writing and have followed your blog for years, finding much good information, a refreshing common sense approach to the practice of medicine, and a basic honesty and humanity that seems to be a rare commodity in today’s “medical industrial complex.”
    I want to comment on one potential problem that might arise with NOACs that I observed in myself. I was initiated on Tikosyn (dofetilide) which works fabulously well. So well that after several months of no AFIB I begged to be taken off Xarelto as I am still bike riding and doing heavy farm work at age 67, and am always cutting or bruising myself with farm implements. My wish was granted, but within a week I noticed a large purple patch on my right lower leg. I thought that I had bruised myself in a big way, but couldn’t remember doing so. I started looking for some information in the literature about potential rebound effects of NOAC’s, and sure enough, there was mention of the potential of thrombosis upon stopping NOAC’s.
    My scary looking “bruise” went away after several days, and I didn’t pursue it with my EP at the time, and I had no other problems, but it certainly gave me pause, and made me think that it might be a more widespread problem worth the attention of EP’s and cardiologists, and discussion with patients who might be taken off NOAC’s on their own request, or for other reasons, like impending surgery, etc.
    Thanks again, Dr. J. I don’t follow Twitter as it is so polluted with trolls & claptrap that I don’t want to support it, but I will always follow your blog entries.

    1. Great comment Joan I also use Tikosyn and with great results. After five years of Tikosyn I’m starting to have more frequent episodes of afib and decided to get an ablation scheduled for early March. Loved Tikosyn for five years but afib has progressed, (I’m 74 years old). I’m on pradaxa and hope to get off it after the ablation.

  3. I am yet another afib patient who has been following your posts for years and treasures them. I certainly take to heart your graphic statement that after even a serious bleed the patient comes out of hospital the same person s/he went in, whereas the stroke patient probably doesn’t. But you do seem rather to glide over the threat of hemorrhagic stroke. About 20% of strokes are said to be hemorrhagic. If I take an anti-coagulant am I not raising my risk of hemorrhagic stroke at the same time as I diminish my risk of ischemic stroke? OK it’s 20 / 80, which still favours anti-coagulation, but it seems to me a pretty scary gamble, particularly as my mother died of a hemorrhagic stroke just after her 60th birthday.

    1. Agree. But the absolute risks of hemorrhagic stroke are much less relative to ischemic stroke. If the risk of bleeding-related stroke goes from 0.3 to 0.6 with an anticoagulant that is a doubling of the risk–but an absolute increase of only 3/1000. 997 people of 1000 are not affected. Compare that to the absolute risk reduction of all-strokes from say 3% to 1% per year. That 2% drop is 66 times greater than the 0.3% risk increase in bleeding stroke.

      1. Thanks very much for that very helpful clarification. In the past I have seen it claimed that taking Apixaban correlates with the least intra-cranial bleed (out of all the anti-coagulants). Could you comment on this claim?

  4. “NOAC drugs have predictable metabolism. That means when I take 20 mg of rivaroxaban it produces the same blood levels of the drug that it would in you.”

    This is not true of Pradaxa/dabigatran, for which relatively low absorption plus two processing stages means that blood levels in people taking the same dose can vary (at a known minimum) 17-fold. The manufacturer knew this before the drug was approved but chose to hide the fact and to prevent the blood test from becoming available, because if it were, that would undercut the selling point that Pradaxa “didn’t require blood tests”, notwithstanding the fact that probably only a single test per patient is needed.

    1. You are correct. It’s true that dabigatran is a pro-drug and has more variability in absorption and clearance. This worries me. Of the three NOACs, I use dabi least often. That said, a recent observational trial comparing r-ban to dabi showed fewer brain and GI bleeds with dabi. It’s not a definitive study but it’s thought-provoking. http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2560376
      What’s more, dabigatran was the only NOAC that reduced ischemic events relative to warfarin.

      1. Pradaxa caused serious bruising and bleeding issues with me in addition to the GI nightmare. There is also known interactions with simvistatin and cardizem that increase levels of all in your system. My skin would tear and rip open with the slightest touch.

        Fortunately, the problems were caught before I had a major event.

        I did well on Xarelto.

  5. I think to be fair you should also mention the relative costs of each of these options. From my understanding the NOACs are much more expensive that warfarin.

    1. Eliquist costs $6000 a year without
      insurance. Yikes!!! Who can you trust will be able to stay on the drug?

      1. Just paid $90.00 for 90 da supply of eliquis Medicare part d . Online pharmacy. I find this cost effective.

        1. Wish I could find your plan. NONE that are available in my area are truly affordable. For example, I am paying $250 per month for generic version of Tikosyn (end of last year, it was $140, so it almost doubled in price), and if I added a NOAC to the mix, my monthly out of pocket would be over $450 just for those 2. The glaucoma med that I got under employee sponsored insurance was $30 for a 2 month supply. Under part D it would be over $100 a month! I had to switch to a less effective alternative drug. This is in addition to the $55 monthly premium, the $400 deductible and the looming dramatic “doughnut hole” increase coming.

          This is seriously wrong, and an outcome of congress writing into the part D law that there would be no negotiating with the pharmaceutical companies on pricing.

          1. Agree Verted and Dr John, pill prices are out of control. I’m always looking for a strategy to cut my price. An ablation scheduled for early March hopefully will get me off Tikosyn and Apixaban.

    2. In the US costs are nearly impossible to discuss because costs vary so much. There are costs to the individual and costs to the system. I agree, for some, it’s prohibitively expensive to take the NOAC.

  6. I to follow your blog faithfully. I am interested in your opinion of the Watchman and when would it be appropriate to consider. I am on Xarelto and have tolerated the drug well.

  7. Dr. John said: “That said, a recent observational trial comparing r-ban to dabi showed fewer brain and GI bleeds with dabi. What’s more, dabigatran was the only NOAC that reduced ischemic events relative to warfarin.”

    Fewer brain and GI bleeds and the least amount of strokes… wouldn’t that matter more for a person of normal weight and renal function than the science behind the NOACs?

  8. Medication Compliance is critical
    for good outcomes. But drug costs are a major reason for poor compliance/.
    Doctors are being judged and paid based on “outcomes”. But doctors cannot control drug costs.This situation exists and no one is paying attention. .

  9. Great post as usual, John. My experience with the NOACs has been positive. I lay out the NOAC/warfarin pros and cons to my afib patients and let them decide. The vast majority choose NOAC if, and this is a big if, they are not cost prohibitive under their insurance coverage. Over the last 5 years I’ve seen the out of pocket costs for most of my patients go down progressively and consequently more and more opting for NOACs.
    I am with you, also, on the LAA closure device, and would not prefer a “mechanical” fix which involves a foreign body inside the heart to taking a NOAC. Personally, I would take a NOAC (and it would be Eliquis) over warfarin even if I had to pay the total cost out of my pocket.
    If Ok with you, I’ll re post your comments on my site (where readers can learn why the TV tells them Xarelto is a bad drug (http://wp.me/p30zF0-1qZ)

  10. Dr J…

    Thank you for your sharing your vast knowledge and continuing education!

    Previously, my hubby completed 23 marathons, 1 olympic tri, and was an avid bicyclist. His activity level has since diminished drastically due in part to his senior citizen status, and starting Eliquis in August 2015 when he had one incident of A flutter and a subsequent successful cardioversion at an ER. He appeared dehydrated at the time, was not using his CPAP, and was going through some home remodeling (major stress) He was also given a pill in the pocket (Metropolol) but never has had to use it. He monitors his BP, has used the Alive Cor app but no apparent recurrences. His CHAD score is 4 (over 65, controlled diabetic with Metformin, hypertension (2.5 mg lisinopril) High Calcium Score) He has seen 3 EP’s, all with slightly different opinions on his course of treatment.

    It is understood that you can not provide individualized treatment advice, but could you speak to the following general questions:

    1) Does a high CHAD SCORE “sentence” a patience to lifelong use of NOAC’s) or can other factors (recurrence rate, ablation, etc) also lead to safely getting off a NOAC?

    2) What is the status of the Eliquis reversal agent? Should this be a continuing concern that the FDA recently failed to approve one?

    3) Can you please explain what the rebound effect of going off NOAC’s actually means. Does the risk increase because there is no protection or does the withdrawal of the drug cause some other type of dynamic to kick in that is troubling? My husband may need to have RTC surgery, and we are concerned about the NOAC protocols involved.

    4) Are all NSAIDS contraindicated, at all times, at all doses, when on NOAC’s? Are there any Anti Inflammatory meds that can be taken when one has an orthopedic injury, etc? Are there any pain meds that tend to be better than others?

    5) Other than making positive lifestyle changes, are there other things that that could have a negative effect and should be avoided if possible… (I’ve read endoscopy and colonoscopy procedures, uncontrolled pain, steroids, stimulants like in Bronchodiolators, drinking cold drinks, could be triggers etc.)

    Thank you for any and all information you have and will continue to provide

  11. Welcome back, Dr. JohnM. I’ve missed your blog posts but now I know what you were up to. I’m going to order your book.

    I have a question regarding one of your December posts. You said you’re going to take up running (10K’s and half marathons). What will you do to avoid knee problems and protect your knees? Every runner I’ve known eventually hurts their knees and has to stop running, whereas bikers can bike indefinitely (I know several in their 70’s who are still strong riders).

    1. For the encouragement of Dr John M, I think late adopters may have more chance of avoiding knee problems than those who have been running hard for decades. I myself am 74, my knees are easily irritated, but I can’t remember when they last stopped me from running. I put this down to low mileage (but with intense short hill and interval running) and Hoka ultra cushioning shoes. On the other hand I know a woman who has subjected herself to an insanely intense ;programme of running and training at all distances forever. She suffers from her back but not her knees. Another friend started running at 65, and 2 years later is competing in ultras with no sign of knee problems. In fact I know quite a lot of older runners, just the people you might expect to have knee problems, we all have our injuries from time to time but I can’t think of one who is being held back by his/her knees. It is certainly not the case that knees are fated to wear out with use in the way that running shoes do. It seems to me that the cause of knee pain is as mysterious as that of AF!

      Go for it, Dr John! You can always go back to cycling later on when the competitive urge has abated a bit.

      1. I ran marathons for 30 years and had to stop running all distances (5k’s etc) because it would trigger PAF. I suspect Dr John as you build distance and speed you will experience this. No fun running half a mile and having to walk and suck air when PAF kicks in. Do you think an ablation is a good solution to this problem? Allowing me (at age 74) to return to short easy running? BTW I read your book and loved it. Great story telling, and medical information for those of us with PAF.

    2. Actually, there is good evidence that running helps rather than worsens arthritic problems of the knees. (http://www.npr.org/2011/03/28/134861448/put-those-shoes-on-running-wont-kill-your-knees)
      I took up running at age 60 after seeing data suggesting that any leisure-time running activity significantly reduces cardiovascular death (http://theskepticalcardiologist.com/2014/10/01/does-any-amount-of-leisure-time-running-reduce-your-risk-of-heart-attack/).
      I have been shocked to find that my chronic knee pain has dramatically improved with the running.
      When I cycle (especially up hill) knee pain is significantly worse and when I play tennis it is particularly bad.
      I also find that when running for the most part I have less tendency to crash and injure myself than cycling.

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