AF Association
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A Big Blind Spot in Anticoagulation Guidelines

Just when we think anticoagulation is the best medicine for people with AF, an article like this is written in Medscape by Dr. Mandrola:

I recently saw four patients in one morning who had atrial fibrillation and either one or two risk factors for stroke. None had symptoms warranting rhythm control or tachycardia requiring rate-control drugs. The only question was anticoagulation. "Doctor, should I take the drug? For the rest of my life? Really?"

The decision to use anticoagulants in patients with AF is a gamble. The drugs lower stroke risk but increase bleeding risk. If the risk of stroke is high, the benefit of stroke reduction exceeds the risk of bleeding. In these cases, we say the net clinical benefit is favorable.

The tricky part is that not all AF patients have the same stroke risk. Everyone who takes an anticoagulant incurs an increased risk of bleeding, so those patients at low risk for stroke may get no net clinical benefit from the drug. The number we must know in this gamble is the risk of stroke without anticoagulation.

Most experts use a threshold of 1% to 2% yearly risk of stroke as the threshold for net benefit of anticoagulation. Both the European and North American guidelines have adopted the CHADS-VASc score as a way to estimate stroke risk.

In the decision to recommend anticoagulation, the guideline writers assume CHADS-VASc scores correlate to fixed stroke rates. And these stroke rates come from Danish national registries.

But what if we looked at different cohorts? Would the rates of stroke be the same?

That is exactly what Drs Gene Quinn and Daniel Singer (Harvard Medical School, Boston, MA) set out to study. In an oral abstract presentation[1] here at the American Heart Association (AHA) 2015 Scientific Sessions, they described and contrasted reported rates of stroke in worldwide cohorts of patients with AF, specifically looking at patients who were not using anticoagulants.

They did a systematic review of all cohort studies and randomized clinical trials that included patients with AF who were not taking anticoagulants. They found 37 eligible cohorts with 563,872 patients from all parts of the world. The cohorts ranged in size from 186 to 186,570 patients.

In a series of slides, Dr Quinn listed the 37 cohort studies. One was immediately struck by the variation in rates of ischemic events across cohorts. In studies that included more than 5000 patients, Dr Quinn noted that stroke rates ranged from 0.45% to 1.97% in North American cohorts to 6.22% in Danish registries. When weighted by numbers of subjects, the average stroke rates for cohorts were North America, 1.86%; Europe, 4.39%; Asia, 3.88%; Middle East, 3.00%.

Dr Quinn then considered 17 of the 37 original studies because they reported stroke rates based on the CHADS-VASc score. The variation in stroke rates among patients with CHADS-VASc scores of 0 to 2 persisted. For instance, in CHADS-VASc 2 patients, baseline stroke rates ranged from 0.48 in the Women's Health Initiative study to 3.71 in the Danish National Patient Registry.

In the discussion section of the oral abstract, they considered the reasons for these large variations. One reason may be that the stroke rates really do vary between regions. But that's hard to explain, given that stroke rates from Denmark are two to three times higher than (phenotypically) similar patients in Sweden.

Dr Quinn felt the more likely reason for variation was due to different methods of data extraction. He cited the Friberg et al paper (published in the Journal of the American College of Cardiology[2]), in which the use of different quarantine periods and differing definitions of ischemic events produced varied stroke rates.

In the question-and-answer period, Dr Quinn showed that there was even variation within the same cohort. He cited two papers from the same Taiwanese database. The stroke rate for CHADS-VASc 2 patients was 0.91 in a 2011 paper[3] and 3.39 in a paper from 2015[4].


Dr Singer reminded me that these observations apply to the smaller fraction of patients with AF who have few risk factors for stroke. He estimated that for more than 80% of AF patients (those with CHADS-VASc scores of >3), the net clinical benefit favors anticoagulants.

That said, AF is a common problem, one that is on the rise. And, as we quantify more and more of the human condition, we will identify increasing numbers of patients like the four I saw on one clinic day.

For these millions of lower-risk patients with AF, there is already significant uncertainty surrounding the decision to use anticoagulants. This presentation adds even more uncertainty.

Like most important scientific observations do, these findings suggest we overestimate what we know. They raise more questions than they answer. Dr Singer likened this gap in knowledge to a large blind spot in the guidelines.

I'd say it is. Think slowly about this for a moment: If we don't know the odds of having a stroke without anticoagulants, we can't possibly know the net clinical benefit. And if we don't know that, we know very little.

That's not good, because when we put an asymptomatic person on a potent drug with the promise of future benefits, we approach the do-no-harm rule.

Perhaps more sobering, as the young Dr Quinn reminded me, is the burden of giving another human being a serious medical condition.

Drs Quinn and Singer made a plea for more uniform ways to assess stroke risk across cohorts. At least then, they argue, we can start the decision from a position of consistency.

That seems a reasonable request, one that we should grant sooner rather than later.

23 Replies

interesting !!


I always thing it strange that patients with AF are so keen to take anti coagulants but reluctant to take a statin because because of their bad press and dislike of Big Pharma. With the price of NOAC's compared to dirt cheap statins and warfarin the manufacturers must be raking it in.

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Gosh that's a lot of information, not all of it relevant. For me the most important point is the point about "do no harm".

I'm not at all convinced that I need to be taking warfarin but just what are the negatives of putting my anticoagulant ratio up to 2.5? Over this last weekend I have been helping my son with work on his classic car. I suffered some rather odd bruising on my fingers. I straight away wondered if my warfarin level was too high. Sure enough my test this week gave a level of 3.8 and so that obviously exceeds the "do no harm" level.

Perhaps I don't really need to be taking any warfarin but will the correct level "do no harm" and provide an insurance policy?

On a slightly different tack, I take a Hawthorn Berry herbal suppliment. Not withstanding the pro pharmaceutical brigades hatred of anything "alternative" I do think that it works for me and it certainly falls into the "do no harm" category.


Hello Buzzard, interested in the Hawthorn Berry, more taken in Germany I believe. May I ask why did you start, did anyone advise you, when did you notice a difference and what brand do you use?

Hope that's not too many Q's. Thanks.


Inevitably, when my AF first started my first visit to my GP coincided with everything being normal. He checked me over and sent me away to monitor the situation. I did a lot of research, self diagnosed PAF and read up on what I could do that wouldn't harm me. Taurine, magnesium and hawthorn berry looked like things that I could try.

I started taking these supplements and things started to improve. Of course I didn't know if it was the suppliments or just an improvement in my condition. I ran out of the Hawthorn Berries (Swanson Hawthorn Berries Herbal Supliment is what I am taking) and didn't get around to replacing them.

My AF started worsening again and so I went back to my GP for proper assessment and received the official confirmation of what I already knew. By this time it had occurred to me that the improvement and then worsening might have some relationship to the Hawthorn Berry supp'.

After my GP and I had decided that I shouldn't go on to beta blockers I did some more research and could find nothing to suggest that Hawthorn was any sort of problem when taken along side warfarin.

I have been taking Hawthorn for about a month again now. I have once again seen a reduction in my PAF episodes. This is really only circumstantial evidence but I'm happy enough to continue taking the Hawthorn on the understanding that it is doing no harm and might be helping.

I must emphasise that, apart from the warfarin, I am taking no other medication.

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Thank you Buzzard!!

Very timely as I am going to see an Alternative Practitioner shortly and will get her view on Hawthorn - take care on the dose as from a distant memory on my research too much or a more concentrated form can be with everything I guess.

The key supplements you use I would agree and Mg and Taurine are in Nutri Ultra Muscleze (an Mg compound) recommended to me professionally and which I have taken for 16 months now.

You don't mention CoQ10 recommended professionally to me to balance the relaxing MG on the heart - I have been taking 200mg/day for a year now.

Lastly, I would add lifestyle changes and supplements are the key to my improvements but I needed the Flecainide to stabilise the condition.


Excellent! Please report back when you've been.

I did have a reason for not taking CoQ but can't remember what it was! Possible reaction with warfarin perhaps?

I'll take a look at the Nutri Ultra and possibly try it when I run out of the suppliments I am using at the moment.


You could be right on the CoQ10 (vague recollection) , I don't take any anti coag as CHADS score 0.


From what I've read, CQ10 is NOT recommended for those on warfarin. I'm often surprised at the number of folks on this site who recommend CoQ10--perhaps they're on NOAC???


Thanks for the confirmation. I knew that there was a reason why I had made a positive decision not to take CoQ!


Hawthorn is good for arrhythmia but battle with warfarin


I'ld be interested in why you say this Susiebelle. I did a lot of research before deciding to take the Hawthorn and could find nothing to suggest a problem. I have now been taking warfarin and Hawthorn together for about a month and I seem to be levelling at about 4mg of warfarin to achieve 2.5.

I don't think that is a particulary high dose is it?


Hi - I read about hoe hawthorn vcan rffect the efficacy of warfarin - if it works for you then brilliant


3.8 in my view is trivial. Higher than 4.5 or 5 gets risky.


That's good to know....I like trivial!


As always ENGMAC a lot to read and some sense there too. At our conference in October (HRC 2015) the question of anticoagulation was discussed at length (isn't it always) with several of us commenting that INR STAR is a flawed program in that it does not recognise rising or falling trends. This was acknowledged by the experts on hand who also agreed that although the best currently available CHADSVASC is not a fool proof predictor of stroke. We were told that work is ongoing to find a better system of predicting a persons risk of stroke but that this may well involve genetic testing along the way.

Bottom line is personal preference. It's been said before that you can always stop taking anticoagulants but you can't undo a stroke. Regardless of any statistics we have to make our own minds up about that question.

Old Buzzard I work on classic race engines every day, still have all my fingers and toes and seldom bruise in fact the worst bruise I had recently was my flu (INR 2.8 at last count.)



More information required Bob. Nothing to do with AF. I suspect that the "classic race engines" that you work on were just race engines in my time in motor sport! My son's car is a Triumph GT6, my time in Motorsport goes back to the mid 1960s.

I'ld be interested to talk further on this subject If you are interested.


Gives us all a lot to consider. Hope studies like this will receive funding and support NOW.


I have atrial fibrillation.

Inthe CHAD score system was 1.

I was originally on warfarin awaiting cardoversions but on that particular occasion my heart was onNSR.

Take off warfarin & leered bisoporal dose.

6 weeks later had a full blow stroke - not allowed to return to teaching& ill health retirement.


Mostly quite straightforward to read and only had one new word!

Although I take an NOAC it has always been my gut instinct not to. l have a CHADSVASC score of 0 - my GP was against anticoagulation, the cardiologist for.

As a non-medical person, the only thing I can compare this with is vaccination. Relatively few people suffered from diphtheria or polio in the Western world before the introduction of a mass vaccination programme in children. However, those programmes are still in place. If they were not, would there be more investment in resources for prevention in, and treatment of, those at most risk?


Well, I'm on warfarin and my risk is 1 (for being female). But my (male) cousin, who has the same thing, had several TIAs at my age so of course, I believe that risk is present and I have to weigh that against the risk of a bleed. Hopefully both are quite low.


The two risks, a stroke and an equally serious bleed are not counter balanced. Its not as simple as take an anticoagulant and though you have reduced your risk of stroke by x you have increased your risk of serious bleed by x. It doesn't work like that. The risk of stroke without anticoagulation is hugely greater than the risk of serious bleed with anticoagulation. The general exception to this is in very senior age.

You just have to look at experiences on this forum. There are large numbers of people who have had strokes/TIAs when they were without protection (and how many are not around to tell us?). Those who have had a serious bleed - and I do mean a serious bleed, at least as life threatening as a stroke - are very few and far between.

Keep taking the tablets.

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I would agree with that. The warfarin guidelines I most refer to state clearly that the higher risk is the risk of strokes, and most bleeding events are minor.

There is another implication. Low INR is much more dangerous than High INR. Therefore, if in doubt in a dosing decision, err on the risk of a higher INR. Put bluntly, an INR of less than 2 is far more dangerous than an INR of greater than 5.


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