Excellent article by Dr Mandrola on the problems of using relative risk analysis in the NOAC versus Warfarin debate .. as well as in all other areas of medicine

As some of you know, I enjoy certain article from the active EP blogger Dr John Mandrola and find them informative and well written, while other topics don't quite ring my bell so much, as in his emphasis on a promoting a 'Less is More' approach in all of medicine including AFIB ablation, that while it sounds appealing on the surface and certainly seems a politically correct stance, its far better in my view that ablationists not marry themselves to doing the least they can get away with, but should be devoted to doing the very best possible job for their patients and not settling for one burn too little to get the job well done.

Preaching a 'Less is More' philosophy to the man behind the catheter, I'm afraid, will wind up leading to far more repeat ablations with poorer overall outcomes if such a view were to be widely adopted in the ablation world, than would be the case by teaching EPs to strive to do exactly as much as is necessary in each case and certainly no less, just because that only sounds sensible conceptually.

In any event, Dr John hit a real home run in his latest blog published yesterday here:

Dr John on a second look at the NOAC vs Warfarin Debate , in his re-look at the NOAC drugs compared to Warfarin by re-analysiing all the date of both past and recent studies from the Absolute risk perspective which reflects more honestly the real world experience and concerns of actual patients compared to the rather tricky and misleading Relative risk viewpoint that is a favorite of Big Pharma in trying a little to hard to portray a pink pig as the golden fleece!

His article says it nicely and kudos to Dr Mandrola for putting this out for the betterment of understanding how these studies can obfuscate the matter at and as easily as enlighten us. Dr John on questions about the real world benefits of the NOAC drugs.[/url].

William Ware who write a Health report Hans publishes here as well make a similar argument in favor of adopting an Absolute risk view and abandoning this misleading and self-serving relative risk view used to make very tiny differences and implied benefits from some new super drug look far more impressive than their real world reality really is.

Looking at not only the hug he 50 times cost difference between the NOACs and Warfarin from the absolute risk perspective, but also in light of the as yet still major issue of no active reversal agent in the field. makes the decision a lot less favorable looking for the NOACs. if these real world risks were properly explained to patients in the beginning. My bet is very few would take the jump when seeing how little difference in absolute risks for them between the two drug classes really exists.

Shannon



Edited 3 time(s). Last edit at 12/21/2013 06:24PM by Shannon.

Shannon,

Great post.

I concur that NNT (number needed to treat) should be looked at on all interventions. I think most people assume NNT's are in the low single digits, when many times they are in the 100's. The NNT means how many people need to be treated for one person to benefit.

Here is a link that isn't tied to Shannon's Medscape account <[search.medscape.com] You'll still need an account to login (free).

Dr. M's footnote:

Some experts have even suggested trouble with warfarin may be predictable. Dr Gregory Lip (University of Birmingham, UK) and colleagues have validated a simple scoring system (the SAMe-TT2R2 score) that uses easily measured clinical factors and might predict either good or bad INR control. A patient with a high SAMe-TT2R2 score might warrant additional interventions, including consideration of a novel anticoagulant.

This describes the SAMe-TT2R2 score <[www.escardio.org]

George

One element that isn't discussed too much is the relative risk of bleeding vs stroke risk with anti-coagulants in general. There is a stroke vs bleed risk calculator for the advisability of blood thinners (I don't remember where I saw it) that does just that.

I'll give my own example....a CHADS2 score of 1, my prescribed post-ablation anti-coag was xarelto (I didn't want to go the warfarin route this 2nd ablation time around). My pre-ablation afib was limited to short runs of less than 5 minutes and occurred only once or twice per month. I had taken the time to read many studies regarding post-ablation stroke and hemorrhage risk and noticed that the aspirin only groups had the least issues with either (although the subjects were usually younger and had lower CHAD scores).

I am an active person at 66, and ride off-road motorcyles, work on roofs, paint houses, etc... in other words, I have a lifestyle that is prone to higher likelihood of collisions with the ground.

So, this second ablation I decided to take the xarelto for 10 days, then switch to 325 mg aspirin, which I did. I felt if I had an afib episode of any duration, I could resume the xarelto. But, as it turns out, I've luckily had no strokes or TIA, nor any afib.

Good move on my part. Athough it has been years since I have had a hard fall, only two weeks ago, I as I was working in a fully-elevated cabover camper I was selling, I somehow managed to trip as I was backing out... I fell nearly four feet down to the concrete, and my head bounced like a basketball. I was woozy and I ended up with a headache...and a bit of whiplash.

I could only imagine what would have happened had I been on the xarelto.

My point? My feeling is that we, as patients, need to carefully evaluate our own circumstances and be an element in the decision-making process regarding both the risks of stroke and bleeding - even covertly, if necessary. I know, some will say this is dangerous... but those who take the time to truly research the issues involved, including their health history, CHADS score, lifestyle, etc...and be very honest about it...may prevent a worsened situation that is the result of the common generalizations used in patient processing.



Edited 1 time(s). Last edit at 12/21/2013 05:06PM by Tom B.

Shannon - When I read this yesterday, I wondered if he was going to address the risk factor of no antidote versus warfarin. I understand his focus which is very good but lacks the one really huge factor that sets the new drugs apart when choosing an anticoagulant which surely would enter into the patient's choices beyond a cost element. Perhaps he is unawae of what you've shared as a result of the Texas trauma center's experiences with risk of bleeding out?

Jackie

Thanks George for the Medscape direct link and not my own account, I changed the link in my initial post as well.

Yes, all the slight of hand using relative risk to make a drug appear to be 50% safer with respect to a single variable when, in fact there is about a 99.4% chance of that never being relevant for any given patient tells a very different story and if these drug risks were explained in the more realistic common sense light, a lot more people would pause before jumping on board.

And TomB, your decision about using Xeralto for the ablation and afterward and then switching off these stronger NOACs as soon as was appropriate is the best way to use these new drugs in my view.

In addition to the lack of an antidote still at the moment, another factor for me in sticking with Coumadin up until my Lariat was because I could test weekly and see just where I was as far as anti-coagulation was concerned. SO far with the NOACS that isn't possible to keep track of. Nevertheless, Xeralto does have some real conveniences when used short term before and in the few months after an ablation for sure.

Once the Factor Xa reversal agent is out, at least then the decision will come down to just convenience and cost and will not include choosing such added risk to one's life as is the case now when these drugs need to be taken long term.

Shannon

It is my belief that diet and nattokinease alone can thin the blood to where the dangerous and deadly drugs are not needed. But that is just me and that is what I did. My opinion and only my opinion since all drugs are damaging to the liver and that liver is vital for healthy blood and healthy blood is vital for good health. Isn't what what its all about? Good health?

Hi ronbn49,

Ive used Cardiokinase which is the strongest and purist new 'N-strain' of Nattokinase for years, and understand well it many excellent properties. However, for people with a documented serious ongoing risk for embolic stroke from the LAA ( left atrial appendage) such as having a documented reduced blood velocity in and out of the LAA below 40cm/sec and an inconsistent A-wave at the doppler inflow of the mitral valve coming from the outflow of the LAA, I would not recommend depending solely on Nattokinase and diet alone without a lot more effort and natural adjuncts to Nattokinase to insure more confidence in being well protected.

Depending on what your whole blood viscosity readings are, Nattokinase will typically reduce an excess viscosity reading by around 20% which is nice but not good enough if you are running a very high whole blood viscosity reading.

You also need to test and treat with sufficient Omega 3 oils and other nutritional adjuncts to make sure your platelet aggregation complex profile, which is typically only found at university research or specialty hemodynamic blood testing labs, have readings approximately 40% above the upper end of the various Platelet Agg test panel reference ranges.

The point being, that just popping a few Nattokinase and eating a decent diet in the face of having an ongoing serious risk of embolic stroke is taking a HUGE gamble with your brain and life. It can work, but not without a whole lot more effort that just some daily Nattokinase and some organic veggies.

With some real ongoing effort and expense, one can gain a measure of confidence using Nattokinase, high dose Omega 3 and other agents needed to confirm your overall anticoagulation status, but most people will simply not do all that is necessary to insure going the all natural approach to anti-coagulation is truly safe.

Thus, I would be very reticent to recommend to people at large to just take some Nattokinase and eat well and suggest all your stroke risk is dealt with on that basis alone. In my book, thats a dangerous assumption or belief for those with a genuinely significant ongoing risk for embolic stroke.

For the average Afibber who doesn't really need to be on anti-coagulation to begin with, its a perfectly good approach to insure added safety, if they are careful to take a verified solid brand of Nattokinase at 100mg dose taken three times a day, once every 8 hours, to insure 24 hour coverage and pay attention to other anti-oxidants and anti-inflammatories from both diet and reliable supplemental sources as well as insuring good hydration each day. For those folks willing and able to both learn all about this approach and follow it rigorously and not just blow off the hard parts and relay only on taking some Nattokinase and these other steps is a good way to go without needing any AC drugs.

But to suggest that is the right approach for every afibber, without a more rigorous testing and confirmation program in place, is tantamount to recommending a good number of afibbers with real built-in stroke risk play Russian Roulette with their brains and thus needs to be a qualified suggestion in that light.

Shannon

Hi Shannon,

With regard to your statement

"For the average Afibber who doesn't really need to be on anti-coagulation to begin with, its a perfectly good approach to insure added safety, if they are careful to take a verified solid brand of Nattokinase at 100mg dose taken three times a day, once every 8 hours, to insure 24 hour coverage"

Please comment on this post by Jackie awhile back in response to Lynn's question, Can I Take Too Much Nattokinase?"

"Lynn - After I just posted my reply to you, I received an email newsletter from Frank Shallenberger, MD, on the topic of taking Nattokinase...
Since it's copy-righted, here's just a segment of the report... on the efficacy. Assuming the information is reliable, this makes taking it easier.

It's great for dissolving clots and lowering blood pressure, which also means it can prevent heart attacks and strokes. But are you taking your nattokinase the right way? A new study says many of us are not.

The researchers in this study looked at 11 healthy men and women from 21 to 65 years old. They gave each person a 100 mg capsule of nattokinase. And then they took blood samples 2, 4, 8, 12, 24, and 48 hours later. They were measuring the levels of nattokinase in the blood. And here's what they found out that can be really helpful for us.

After the participants took the capsule, the blood levels of nattokinase gradually increased until they reached a maximum at 13.3 hours. Why is this important? Because the usual instructions for taking nattokinase is to take it three times a day. But this study is showing that it doesn't reach its maximum blood level until after 12 hours.

So instead of taking it three times a day, twice a day is actually better. That's important because remembering to take anything three times a day is difficult. But popping your nattokinase first thing in the morning and then again right before bed is easy.

Frank Shallenberger, MD
REF: Ero MP, Ng CM, Mihailovski T, et al. A pilot study on the serum pharmacokinetics of nattokinase in humans following a single, oral, daily dose. Altern Ther Health Med. 2013 May-Jun;19(3):16-9."

Louise

And I would assume that I am one of the people that needs to stay on Xarelto for now....having had a LAA isolation in September. Kind of scary to hear you say that people like me have a 'serious risk of an embolic stroke",,,,ahhh!

According to Dr. Barrett, there are some things they can do if you require an antidote, just not sure how effective that is..?

Barb

Well, then there is me---I cannot take Coumadin, it caused the whites of my eyes to get bloodshot, just a little pressure and my thumb filled with blood. I was told by my EP to stop the Coumadin. I saw my EP about a month ago and asked him about the other blood thinning drugs and he said that I would react the same way as I did to the Coumadin. I do take some aspirin, my CRP is 0.28 (<0.80 Mg/dl), Homocysteine 8.7 (<10.4 umol/L).

About 3 weeks after stopping the Coumadin, I had a nose bleed and spit up some blood clots from my throat. Coumadin must have done a number on me, if I take aspirin everyday, I get bad bruises.

Liz

Hi Louise,

Thanks for the reminder about the more recent small study on Nattokinase. I fully believe the results and it follows clearly what has been known for some time about its benefits.

Keep in mind that I AM a big believer in using it appropriately.

I also am sure that is will help reduce the risk of clot formation in most cases where there isn't a more significant driver or substrate that might more seriously encourage clot formation within a very delayed velocity LAA. And/or within an LAA that has one of the more unhandy morphological shapes such as Cauliflower or Cactus shape rather than the less risky Windsock and particularly the Chicken Wing which is significantly more favorable in terms of lessening stroke risk from the LAA.

However, while its fine for anyone who is really going to dedicate themselves to aligning with cutting edge MDs who understand the issues of Whole blood viscosity management and the use of Nattokinase and other viscosity lowering natural agents as well as sustaining life-long proper hydration and who will, for sure, do the regular essential testing for at least the first three to five year, including at least one or two TEE exams after optimizing their supplement-based anti-coagulation program to confirm it is really working, to encourage such folks to go for it!

Particularly if they have something like a more or less CHADS 1 to 2 max level of stroke risk and a more favorable LAA Morphology.

However, accepting and adopting such a protocol which has Dramatically less research behind it at the moment, the person has to be very clear of the added degree of uncertainty, at least until they can get repeated confirmation from their own careful and repeated serum testing that their protocol titration is really working well in their case by using TEE to confirm the complete absence of any thrombus in the LA or LAA as well as absence of any SEC ( spontaneous echo contrast) in these structures as well.

If you, or anyone else, is truly willing to go to these added lengths for verification under the guidance of a smart and knowledgeable MD who clearly understands hemodynamics. Then at least for such a person I would give this qualified acknowledgement that it can indeed work.

However, I also know all too well how human nature is, and so many of us really just want to be given a ready made protocol and some reassurance that is should work and will then gradually skip the testing and wing it.

It is this larger group of Afibbers, who if they are really honest with themselves witll know who they are, that I am too nervous about giving some blanket declaration that Nattokinase and a good diet are all that is needed base on the fact that they can definitely help, plus an added large dose of good faith but little else. That being the case, more often than finding the really dedicated and committed researcher and person who knows how to manage and learn the nuances of supplemental protocols ( think Jackie, GeorgeN, Hans, myself and a handful of others here), My sense is that most folks are not inclined to delve so deeply into this subject with the degree of commitment necessary to do this with reasonable safety. And so that is why I am so loath to recommend going this route, carte blanche and across the board, simply because it 'can' be made to work.

Do you appreciate what Im trying to convey? Im not at all knocking Nattokinase, but even this very encouraging small study of 11 people not withstanding, it is still a far cry from the kind of repeated larger scale in-depth randomized placebo controlled trials that might well reassure all of us as to its real world efficacy.

I DO feel that the majority of afibbers can benefit from carefully selected brands of known high quality Nattokinase.

Its interesting too this new report that shows a max effect around 12 to 13 hours for Natto, but Dr Holsworth and Dr Wright who are among the world best experts on Nattokinase, and both of whom I have spoken with about this issue, reinforced to me in my case that the safest approach is a three times a day dosing paying real attention to making sure your last dose is taken just before bed as during sleep and early morning hours is when the blood borne building blocks of an LAA thrombus is most likely tot be at peak blood levels and thus making sure you have a full peak level of Nattokinase throughput the night and early morning makes real sense! Dr Holsworth even recommended I take four 100 mg dose, one every 6 hours and the last one right before bed, in addition to a complete blood cleansing/viscosity lowering program using very large nightly doses of a high purity Phosphotidyl Choline as well to improve endothelial cellular functional.

Even with the peak of Nattokinase effects at 13 hours, taking it every 8 hours will only reinforce a very solid and consistent blood level with less chance for little dips a couple times a day as might occur with twice a day dosing.

Again, if you are a person with lone AFIB and minimal stroke risk who just wants to be sure they have reasonable protection on board, and wants to use Nattokinase instead of the aspirin still recommended by too many EPs who are not familiar with Nattokinase and its superiority over aspirin for this function, then by all means take it twice a day and I'm sure you will be fine.

But for those with sleep apnea, or significant hypertension, low LAA velocity and stroke unfriendly LAA shape, prior stroke or TIA etc ... I would much rather err on the side of making sure I was well covered using perhaps an Anti-coagulant drug while exploring getting a Lariat or Watchman for long term freedom from drugs. And if you are sure your nature will not sabotage your safety by cutting corners and you wish to go not only the all natural stroke reduction program with Nattokinase and with the full natural program laid out above, then rather than guess that twice a day Nattokinase ought to do the trick and wind up being wrong in a bad way, I would not cut any corners at all in that drug free AC program and be very vigilant in testing to make sure you maintain a clear LAA and LA.

Shannon

Even though I have had a Lariat and now have less stroke risk than a healthy 25 year old person without AFIB, I still take Cardiokinase each day for its wonderful blood viscosity lowering properties.



Edited 3 time(s). Last edit at 12/23/2013 08:07PM by Shannon.

Thank you, Shannon, for, as always, providing a clear picture.

Louise