What treatment for Dr Topol's 91-year-old mother-in-law post-TIA?

This challenging case illustrates how digital medicine speeds up diagnosis through the simple identification of atrial ectopic beats (iPhone ECG) and the ability to confirm AF (a 14-day iRhythm period). Pending the MRI, and with these data under your belt, what would you prescribe for Dr Eric Topol's 91-year-old mother-in-law? 

Disclosure:

Dr Topol's mother-in-law agreed to this presentation
Dr Topol has no conflicts of interest relevant to the digital technology he presents

See also:

The creative destruction of medicine with Dr Eric Topol
RE-LY: Dabigatran bleeding-related gene variant could herald personalized dosing
Combining wireless sensors and genomics for CVD prevention?

Dr Eric Topol: I'm going to do something I haven't done before on Topolog: present a case from my extended family.
 
My mother-in-law, 91 years old, recently had a TIA, which occurred the day after our daughter's wedding, where she had some alcohol and was very active. The following afternoon she complained that she could not move some of her fingers on her left hand. On exam, it was clear that there was motor difficulty, no sensory loss, and that it was confined to the movement of her hand. I saw her and did a phone electrocardiogram, and that showed that she had a frequent atrial ectopy (although she was not in atrial fibrillation). I was suspicious, however, that that might have been the case. But not wanting to take care of my mother-in-law—who was perfectly healthy at age 91 except for hypertension (which is well controlled)—I had her see a neurologist. At the same time I ordered an iRhythm so I could  potentially capture whether or not she manifested atrial fibrillation intermittently. She never had any symptoms of light-headed dizziness, palpitations, or anything that would suggest a history of atrial or supraventricular tachyarrhythmias.
 
She went to see the neurologist, and she's scheduled to have an MRI scan. We got back two weeks of recording of the iRhythm and it showed that she had quite a number of episodes of intermittent atrial fibrillation. So that whole story is likely the cause. She also had a carotid ultrasound Doppler, which was completely normal. So I'm guessing this was the culprit.
 
And that brings up the next question: Whether to treat her with aspirin, warfarin, or one of the new anticoagulants (whether it's dabigatran or rivaroxaban or, if it ever does get approved, apixaban)? These are three alternatives. Now, dabigatran might be interesting. However, the recent European Society of Cardiology Congress report about this variance in CES1, which is correlated with at least a third reduction in significant bleeding, would be nice to  know, but we don't have a commercially available genotype assay, and we would like to see replication and publication of that—what would be considered a seminal finding. So with that put aside—whether to use rivaroxaban or apixaban—what is the best treatment, or just using aspirin, in a woman of her age to prevent the risk of atrial fibrillation? I'm particularly concerned because of its intermittent nature, thereby increasing the risk of TIA and stroke.
 
At the moment she is on aspirin and doing well. This is a tricky case: it brings into play multiple points of digital medicine:
(1)   The ability to see the atrial ectopy on a phone cardiogram during the episode of the TIA.
(2)   The ability to diagnose atrial fibrillation that was not at all infrequent during a 14-day extended recording.
(3)   If we have the capability of digitizing the CES1 gene variant to know whether or not she would do well with dabigatran or would suffer potentially, at her age, a higher risk of bleeding from this drug and probably similarly from all of the newer anticoagulants as well as warfarin.
 
I'd be interested in your views as to your recommendations for my mother-in-law. She's doing very well right now, I'm pleased to report. Her MRI test is pending, and hopefully she will not have any further cerebrovascular events in the future.
 
Thanks very much for your attention to this segment. I'm certainly trying to emphasize the individualized treatment here, whether it's using digital means of assessment of treatment, and also connectivity to you for your input. Thanks very much.

Your comments

	What treatment for Dr Topol's 91-year-old mother-in-law post-TIA?
	# 1 of 47	December 1, 2012 12:00 (EST)
	Dr David Chase	Dear Dr Topol, thanks for sharing your experience. At 91 years age, coronary artery disease may not have been entirely ruled especially if your mother-in-law was asymtomatic. I believe Aspirin alone best covers that possibility as well without predisposing to an increased  bleeding risk. Very recently, as a family, we ourselves had to go through this exercise with my father-in-law's treatment and the same issues cropped up. Thanks again. Dr David Chase
	# 2 of 47	December 2, 2012 12:00 (EST)
	Eric Topol	Thanks for the great input here. The MRI showed only a small infarct corresponding to her motor deficit, that was transient (<24 hrs). The input on use of apixiban is interesting but not available. The use of dabigatran is tricky since the 75 mg qd dose was never tested and the 150 mg dose is the only one approved (recall the 110 mg dose in the trial, with efficacy, was not ever approved).  Agree she is at high risk for a recurrent cerbrovascular embolic event. She is not interested in taking warfarin. Dr. Sigwart suggested a drug to suppress the intermittent AF (flecanide) but I am not enthusiastic about that. So await your further input on best shot at recommendations for her......
	# 3 of 47	December 3, 2012 12:00 (EST)
	DH	I posted a much longer message but the system would not accept it. Her CHADS2-VASc score, even without the neuroimaging showing an infarct, or without documented CAD, aortic atheroma or PAD, is 6; meaning she has a 9.8% per year risk of stroke or systemic embolic event. Here in Canada, we have dabigatran 110 mg BID which is used as a 'fudge' factor in patients at higher risk for bleeding on dabigatran 150 mg BID or dose-adjusted warfarin with a target INR of 2.5. I realize the FDA never approved that dose, which is too bad. I would not use ASA, as its efficacy for secondary stroke prevention in EAFT was trivial compared to warfarin. It would expose her to bleeding hazards but give very little benefit. I would suggest full dose dabigatran plus a proton pump inhibitor given at bedtime (which would allow some spacing between the dinner time dosing of dabigatran). I wonder if testing for CES1 has ever been shown to reduce outcomes like bleeding in a randomized trial - my guess is 'not'. It's too early. There are many other factors involved in bleeding and some of them relate to pure serendipity (for example, having a friable cecal polyp which is not known to the patient, or getting into a motor vehicle collision). I have many very elderly patients on oral anticoagulation who have done well for years without stroke or bleeding complication. May she be one of them. If you are worried about the bleeding risk of dabigatran, you could try gently dosing warfarin and aiming for an INR not much higher than 2.0 (and accepting as low as 1.7 to 1.8).  Personally I would prefer a bleed to a stroke any day (even an exsanguinating bleed leading to death).  Hope this time this gets posted.
	# 4 of 47	December 7, 2012 10:45 (EST)
	Barbara Roberrts	91 year old This is a really tough one. I would tend to go with warfarin, keeping her nearer to an INR of 2 rather than 3. I am worried that given her age and gender, she is probably at higher risk of both recurrent emboli and bleeding. I am concerned with the lack of ready reversibility with the newer agents should she bleed. Barbara Roberts, MD Author's disclosure (Dec 7, 2012) I have no relevant disclosures to make in connection with this topic.
	# 5 of 47	December 7, 2012 12:01 (EST)
	ashfaq shuaib	91 year old patient with a TIA I am not sure if this is a TIA or a minor stroke. The MRI should be done within 24 hours and not several weeks later as this will help determine the size of the ischemic lesion, a marker of subsequent risk of recurrence(and r/0 hemorrhage and other lesions). Her risk of suffering a large disabling embolic stroke is very high and the risk of hemorrhage on AC relatively acceptable. She requires renal funtion testing and if normal I will recommend either lower dose of Dabi (110 mg BID...unfortunately not available in the US) or Riva 15 mg OD. Leaving her on ASA is not a very good option....no benefit and with risk of GI complications. Hope this is helpful I will recommend either Author's disclosure (Dec 7, 2012) I have no relevant disclosures to make in connection with this topic.
	# 6 of 47	December 7, 2012 12:06 (EST)
	Fernando Bassan	High risk This patient present as high risk for stroke, as assessed by Chads or ChadsVasc scores. As you mention that she is perfectly healthy, i assumed that she hasn't high risk features for bleeding (except for age). So, i think she deserve anticoagulation, and i would go first on warfarin, seeking an INR of 2. Author's disclosure (Dec 7, 2012) I have no relevant disclosures to make in connection with this topic.
	# 7 of 47	December 7, 2012 01:16 (EST)
	Canio Casale	What about the treatment of the of the paroxysmal A.F.? Why you haven't said anything about the treatment of the Paroxysmal A.F.,which is the cause of the Cerebral Embolism? Author's disclosure (Dec 7, 2012) I have no relevant disclosures to make in connection with this topic.
	# 8 of 47	December 7, 2012 05:13 (EST)
	Ken Gruchalla	Use of antithrombotics in the advanced elderly with AF With the recent approval of ELIQUIS (apixaban)for stroke prevention in atrial fibrillation (SPAF) earlier this week in Canada, there is now information in the public domain that may help to inform this issue. For the novel oral anticoagulant (NOAC) class of drugs, we have provided both efficacy (total stroke and SE) and safety (major bleeds) data for all drugs, ie. PRADAXA, XARELTO and ELIQUIS across different age tranches, as well as by degree of renal impairment, in our product labeling, as observed in the SPAF pivotal trials. Of note, you will see that for all of these products, the absolute rates of stroke and major bleed increase for both increasing age and worsening renal function, as expected, for those less than 65 years, compared to those over the age of 75 years at study entry, irrespective of the anticoagulant used. However, for effects relative to comparator (generally warfarin) there are some noteworthy observations in respect of action over increasing age. 1. For dabigatran, at either the 110 mg or 150 mg bid dose, the reported advantages in terms of major bleeding over warfarin are much attenuated, and in fact appear to be lost, with increasing age over 75 years (and more so over 80 years). For example, in those over 80 years (about 3,000 pts across three study arms), annual event rates for major bleeds, of 5.3% for dab 110, 6.2% for dab 150, and 4.7% for warfarin were seen, while in those less than 65 years, significant hasard ratios of about 0.35 for both dab doses were reported, compared to warfarin (also about 3,000 pts across three study arms). For stroke, both dab arms have HRs about 0.67 (borderline NS), compared to warfarin, in those over 80 years, so the dab 150 mg dose advantage over the low dose is not seen in these patients. 2. Although both doses of dab have been approved for SPAF in Canada since October 2010, the high dose of dab 150 mg bid has never been recommended for those over the age of 80 yrs, on the basis of risk/benefit considerations, and is relatively not recommended in those over the age of 75 years, see our product labelling. 3. The trend to relatively more bleeding, and relative loss of effectiveness with age (at least for dab 150), compared to warfarin, is not seen with rivaroxaban or apixaban. 4. Currently, for apixaban only, we have reported some data for those over the age of 85 years from both of the pivotal studies. There is no indication of a "tail" risk not in line with overall study results. For example, in ARISTOTLE, while the study HR is 0.79 (SS) for stroke and SE for apixaban over warfarin, in those over 80 years the HR is 0.81 (NS) and 0.35 (SS) in those over 85 years of age. In AVERROES, the study HR is 0.45 (SS) for stroke and SE, and 0.14 (SS) in those over 85 years. The cost, in terms of major bleeding, is stable across all age tranches at about 50% increased, and not increased further in those over 85 years. There is no indication of increased fatal bleeding or ICH in those treated with apixaban, compared to warfarin, including in those over the age of 80 years. Note that ASA did not perform well at all in terms of stroke prevention in AF with absolute annual rates of over 6% in those over the age of 75 years, compared to under 2% in those treated with apixaban. Those interested may consult Canadian labelling for more information re event rates across age and renal function at: Enter the product name and click on any DIN number, then again on the pdf link for our Product Monograph (name of Cdn labelling). Note that the SPAF updated ELIQUIS PM will be posted in about a week's time. Note that all information is for reference purposes only and prescriptive material in the label is for Canadian prescribers only. Ken Gruchalla, MD Cardio-Renal Division Health Canada e-mail: ken.gruchalla@hc-sc.gc.ca Author's disclosure (Dec 7, 2012) I have no relevant disclosures to make in connection with this topic.
	# 9 of 47	December 7, 2012 05:33 (EST)
	Ken Gruchalla	Health Canada web address re drug product labels http://webprod5.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp Author's disclosure (Dec 7, 2012) I have no relevant disclosures to make in connection with this topic.
	# 10 of 47	December 7, 2012 06:58 (EST)
	Mervyn  Sahud	High risk candidate requires lab monitoring to achieve the "sweet spot" Even after excluding thyroid and electrolyte issues, the risks are high both for thromboembolism and bleeding in a 90+ y/o woman who I believe would do best with either Xarelto or Eliquis ar reduced dosage pending the laboratory monitoring with an anti-Xa assay that would achieve stable plasma level. Until that assay reaches commercial access a Prothrombin time of 18-20 secs. could be the best surrogate. I do not believe aspirin is effective in this situation. Author's disclosure (Dec 7, 2012) I have no relevant disclosures to make in connection with this topic.
	# 11 of 47	December 8, 2012 04:09 (EST)
	svetlozar sardovski	91 old with TIA 1. First I would give her Amiodaron to prevent or decrease the number of episodes of AF. 2. Second: The risc for bleedeng with aspirin and warfarin is almost the same but not the same is effect for prophylaxis of trombebolism. So it is not wise to take aspirin.I would give her Dabigatran 75mg bid or less 110mg daily depending of her GF. ssardovski@yahoo.com Author's disclosure (Dec 8, 2012) I have no relevant disclosures to make in connection with this topic.
	# 12 of 47	December 9, 2012 01:20 (EST)
	Kishore Shetty	consider no treatment option! I want to give a totally different perspective for discussion. Ask what she would like to do after explaining the options. First the circumstances causing the event: Even though it is happy event for her, attending grand daughters wedding; for a 91 year old can be very tiring. You won't realise till you are of that age. Ask her how tiring it was for her. I don't how much alcohol she normally has, likely none, consider her age and metabolism and think of its effect on heart rhythm. Consider how untypical the day from her normal routine for her. Her CHADS VAsc score is 4. I would do an echocardiogram as well though it general doesn't help in risk stratification, may find unsuspected cardiac abnormality sometimes even in 91 years old. Although paroxysmal AF is risk factor there is debate on how much of it is a risk; Is such short duration really a risk factor? Last but important part is treatment; here should she prefer treatment what she should have. Not an easy one. Think of risk of bleeding and reversal and experience physicians in managing. I would with out doubt go for warfarin; we know how to use, ability to monitor is a real advantage not a disadvantage and we know that most risks of bleeding is with INR greater than 3. Disadvantage with newer agents lack of effective quick way of reversal in case of bleeding. Also trial data shows efficacy. They are never about safety and risks. This becomes apparent in general population once drugs are in wide use, which information we don't have with the newer agents. Trials are done, necessarily, in is selected group of patients. How many were in their 90s in the trial. (Just think of rosiglitazone) Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 13 of 47	December 9, 2012 04:31 (EST)
	Kishore Shetty	error CHADS Vasc score is 6 not 4 as she had TIA making adjusted stroke risk nearly 10% per year Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 14 of 47	December 9, 2012 07:38 (EST)
	Eddie Vos	Maybe not drugs .. At age 91, is "treatment" really what she would prefer? Clearly, regular blood draws to check INR for warfarin are not a quality of life advance. Not being a physician but having followed the field for decades here's what I'd suggest: How about reducing coagulopathy by other means, for example by gradually increasing vitamin E from 300 to 600 IUs, if tolerated a fish oil pill early in a meal say 3 or 4 times per week and a fairly high dose no-iron multivitamin, such as the no-iron Twinlab Daily-One-Caps taken with a meal. Many components in such multi affect coagulopathy and vascular health while reducing homocysteine, one of the top risk factors [likely causal] for stroke. I'd be interested knowing her Hcy that in many at that age [NHANES, Rotterdam home-bound elderly] may well be over 20 µM, i.e. "stroke city". Then, possibly, a 1/2 an aspirin every second or third day if she's not bruising currently. All these avenues are OTC and likely more acceptable at age 90+ than drugs for which the evidence in preventing a serious clotting event are iffy at best. Spending time at the doctor and pharmacy are stressful and not quality of life benefits. Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 15 of 47	December 9, 2012 07:47 (EST)
	Melissa Walton-Shirley	Eddie, No data I am unaware of prospective randomized controlled trials with "fish oil" for stroke reduction. Extrapolating studies with aspirin, aspirin plus clopidogrel, compared with warfarin, warfarin is the best bet, the combintation the second best bet and aspirin the least effective though better than nothing. Most of us hope to be a functioning 91 year old some day. If I make it that far, I would hope that I'd be treated the same as if I were a healthy 82 year old provided we look the same on paper. Since our mode of exit is likely stroke or heart attack if I've already had a stroke or TIA, prophylax me please against another with something that is actually proven to work. Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 16 of 47	December 9, 2012 06:05 (EST)
	Flavio Reich	laa closure how about left atrial closure? f.reich m.d. Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 17 of 47	December 11, 2012 08:38 (EST)
	Carl Adler	what next? What did the echo show? is she at risk of more a.fib? Primum non nocere; what is her hypertension med? there is no way she should go on warfarin; is her tia really from the a. fib or small vessel disease of the brain and the a. fib is really a red herring? Use wisdom and not knowledge; if it was me personally i would use aspirin and omega 3 but i don't have to worry about the lawyers when treating myself Author's disclosure (Dec 11, 2012) I have no money but will accept voluntary contributions.
	# 18 of 47	December 11, 2012 02:40 (EST)
	Stephen Algeo	Warfarin Option Warfarin therapy with home monitoring of INR can be a useful option in a situation like this. It might be hard for a 91 yr old to master but can easily be done by a family member. This allows very careful adjustment of anticoagulation therapy from home with a simple fingerstick. Author's disclosure (Dec 11, 2012) I have no relevant disclosures to make in connection with this topic.
	# 19 of 47	December 11, 2012 11:45 (EST)
	James J. King	Measure the blood’s Zeta Potential She’s 91 years old. She needs to walk barefoot on the beach in Hawaii. Drug treatments is the fine line between help and harm. Now for something complexly different for treatment of afib and strokes! Aspirin, Warfarin or the new oral anticoagulants may replace warfarin may soon be standard of care. At the turn of this millennium, several new oral anticoagulant medications, which are designed to be given in fixed doses without coagulation monitoring. Walking barefoot will raise her Zeta potential and lower her BP. The greater the zeta potential the more likely the blood is to be stable because the charged particles repel one another and thus overcome the natural tendency to aggregate. The measurement of zeta potential is often the key to understanding afib and strokes. Electrostatic repulsion of blood particles is often the key to understanding the stability of patient's blood. Author's disclosure (Dec 11, 2012) I have no relevant disclosures to make in connection with this topic.
	# 20 of 47	December 14, 2012 02:58 (EST)
	D Hackam	I agree with Dr Shuaib Dabigatran 110 mg BID would be ideal, but is not available in the US (for reasons that mystify). Rivaroxaban 20 mg would probably be an effective alternative. Author's disclosure (Dec 14, 2012) I have no relevant disclosures to make in connection with this topic.
	# 21 of 47	December 15, 2012 09:09 (EST)
	chau Huang	TEE for cryptogenic TIA/CVA This case can be a lacuna infarction from hypertension related small vessel disease rather then short duration of PAF causes cardiogenic emboli.Therefore, the TEE evaluation of LAA is a part of work up. Author's disclosure (Dec 15, 2012) I have no relevant disclosures to make in connection with this topic.
	# 22 of 47	December 17, 2012 08:16 (EST)
	Carl Adler	so what ended up happening? more tests? what treatment given? Author's disclosure (Dec 11, 2012) I have no money but will accept voluntary contributions.
	# 23 of 47	December 17, 2012 09:53 (EST)
	Stephen Pollock	afib in a 91 any consideration for rhythm control with amiodarone? Author's disclosure (Dec 17, 2012) I have no relevant disclosures to make in connection with this topic.
	# 24 of 47	December 18, 2012 09:13 (EST)
	Eric Topol	more info, input ? Appreciate all the excellent input. Echo (by Vscan, part of physical exam) showed a mildly enlarged left atrium , but otherwise normal. Reluctant to use amiodarone; ECG also shows bifasciular block (RBBB + LAHB). Without ability to get dabigatran 110 mg bid, what is experience with 75 mg bid or 150 mg qd out there? Author's disclosure (Dec 18, 2012) I have no relevant disclosures to make in connection with this topic.
	# 25 of 47	December 18, 2012 02:17 (EST)
	D Hackam	interesting I just had a patient who had an embolic stroke on dabigatran 110 mg BID. This resulted in central retinal artery occlusion. Prior to that she had a cereballar stroke on ASA monotherapy (cerebellar). She is now on dabigatran 150 mg BID for AF. In a sense, perhaps the FDA reviewers were correct that 150 mg is the optimal dose that balances risk and benefit. Unless she has quite severe renal insufficiency, I would not use 75 mg BID. Even then, there is no outcomes data for that dose - it is all based on PK modelling. Author's disclosure (Dec 14, 2012) I have no relevant disclosures to make in connection with this topic.
	# 26 of 47	December 18, 2012 02:28 (EST)
	D Hackam	PS In case you are thinking this was a compliance issue, I asked repeatedly and she said she never missed a dose of her 110 mg BID dabigatran, because she knew it was important. The stroke resulted in complete monocular blindness (irreversible). Her CHADS2 pre-strokes was only 1 (hypertension was her only risk factor). The first stroke was silent and picked up on neuroimaging for headaches. Author's disclosure (Dec 14, 2012) I have no relevant disclosures to make in connection with this topic.
	# 27 of 47	December 19, 2012 06:58 (EST)
	Eddie Vos	What does she prefer ? Baby warfarin Eric, question: what does she want to do? I think one has to be careful not to have a "creative destruction of life quality" [I have your excellent book of related name]. I forgot to mention earlier plant based n-3 [say total 2g/d; sources: canola, flax oil, flax-oil pill if you must] that may be the most antiarrhythmic of the fatty acids [Alex Leaf's work, LYON]. I'd be surprised she's not bruising already on a full daily aspirin ... doesn't one get the same antiplatelet effect on 1/2 an aspirin every second day? Isn't there something like a "baby warfarin" for which no INR is indicated and for which there is at least an antidote -- as opposed to a short half-life / high-cost / low-science -gatran or -xaban. Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 28 of 47	December 19, 2012 11:02 (EST)
	Eduardo Ramirez	aspirin ? What is the experience with aspirin in a 91 year old patient, preventing stroke in atrial fibrillation ?. I don't think is the best option. Author's disclosure (Dec 19, 2012) I have no relevant disclosures to make in connection with this topic.
	# 29 of 47	December 19, 2012 05:49 (EST)
	Carl Adler	let's reason together first - it still has not been determined if her "event" was related to the a.fib or something else, so if that is the reason there is no justification the next issue is if she does indeed have a.fib and is at increased risk of an event, should you do anything; once again the doctrine of Primum Non Nocere holds; I had a patient who had two valves replaced and was given metal valves and placed on coumadin and died from an intracerebral bleed; oh how the cardiologist bragged how they "saved" his life because he couldn't survive with those valves; they should have put in pig valves and then no coumadin - never the less they were heroes; he didn't die of "heart disease" back to the story - if you decide to do something beyond the safety of omega 3 and aspirin and were chosing between pradaxa and coumadin - go with pradaxa; there is increased risk of bleeding but not fatal ones (of course those studies didn't have nonogenerians but the what can you expect) Author's disclosure (Dec 11, 2012) I have no money but will accept voluntary contributions.
	# 30 of 47	December 20, 2012 08:13 (EST)
	Carl Adler	will By the way - how you treat her depends what she will leave you in the will Just kidding, of course Author's disclosure (Dec 11, 2012) I have no money but will accept voluntary contributions.
	# 31 of 47	December 20, 2012 11:42 (EST)
	Eddie Vos	Moderator: please remove post 27 It's unbecoming and of exceptional bad taste. Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 32 of 47	December 21, 2012 11:40 (EST)
	Flavio Reich	to dr. hackman i had a pt who had a massive stroke with coumadin inr 2.4, there's no garantee that even if you're well anticoag there's no stroke risk. the problem with my patient was that we could'nt use lysis. this is the same with new anticoag, cause in coumadin pts if the inr is low you can use lysis, but with 10-a inhib nobody knows. Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 33 of 47	December 21, 2012 12:48 (EST)
	D Hackam	to flavio reich I agree, and the fact that the stroke/SEE rate in dabigatran 150 mg treated patients in RELY was above zero confirms your conclusion. However, my argument was that there was a higher probability for stroke/SEE in my patient when treated with ASA or dabigatran 110 mg BID (both of which resulted in subtherapeutic levels of anticoagulation in a patient with normal renal function, normal body weight, and normal age, with no bleeding risk factors). This is likely why FDA never approved dabigatran 110 mg, because clinicians would resort to it inappopriately (as was done in the case I saw). One could give the equation that ischemic stroke risk, for any given patient (with no other variables changing), is higher in ASA > dabi 75 mg bid > dabi 110 bid > dabi 150 bid. Of course it should be pointed out that these 4 options have never been compared directly in a head-to-head trial and thus I am relying on indirect comparisons - hence the "art of medicine". Author's disclosure (Dec 14, 2012) I have no relevant disclosures to make in connection with this topic.
	# 34 of 47	December 21, 2012 03:46 (EST)
	Kishore Shetty	what is therapeutic dose? Dr Hackam makes an important point. Is 110 mg dabigatran subtherapeutic? There was an interview with Salim Yusuf before the RELY study was published, which since then has been removed by theheart.org, wish they would put it back, where he talked about the importance of having warfarin naive patients on trial and also getting the dose right with new agents; hence the two doses of dabigatran in the RELY trial. The risk benefit not only depends on the dose but also on the patient characterstics; sex, age, renal function, co-morbidities etc. So the newer agents can be subtherapeutic or excess dosage and the risk benefit will vary. Not having a test to know if the dose is therapeutic or not is a limitation. The art of medicine comes here. Trial data tells you what sort of benefit you can expect should you decide to use the drug. Data gives you information not instruction. Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 35 of 47	December 21, 2012 09:27 (EST)
	Stephen Algeo	Still like warfarin Let's say we agree anticoagulation is needed in a 91 yo (obviously not all agree). I still maintain the safest approach is warfarin therapy with home monitoring of INR by weekly (or more often) fingerstick. I would be very wary of using any of the new anticoagulant agents in any dose in this age group. The real world experience with these agents is what counts, not randomized trials, and we are seeing a sobering number of serious bleeds with these drugs in the elderly. Author's disclosure (Dec 11, 2012) I have no relevant disclosures to make in connection with this topic.
	# 36 of 47	December 22, 2012 10:35 (EST)
	James J. King	Since she is not interested in Coumadin As of yet, there aren't any blind studies which demonstrate that any natural alternative is as effective against stroke as Coumadin. Natural blood thinning alternatives, such as: (1) Grounding – connecting to the Earth’s electromagnetic energy has been shown to help improve zeta potential, the tendency for red blood cells to repel one another. Grounding is also cardio-protective in that it can support heart rate variability and can help reduce stress by relaxing the body (as shown through increased parasympathetic nervous system activity). (2) Krill oil – 1 grams daily (Best is NKO, Very well tolerated) (3) Bromelain (an enzyme derived from pineapple) – 600 mg daily; (4) Nattokinase - an enzyme extracted and purified from natto, a traditional Japanese soybean dish. Nattokinase is a good supplement to take to help thin the blood. It helps prevent blood clots by reinforcing the actions of plasmin, an enzyme in the body that breaks down fibrin – 100 mg daily; (Tastes like shit) Author's disclosure (Dec 11, 2012) I have no relevant disclosures to make in connection with this topic.
	# 37 of 47	December 28, 2012 08:24 (EST)
	Eric Topol	Apixiban approval With the approval by FDA today, will plan on using 2.5 mg bid Thanks for all your input! Author's disclosure (Dec 18, 2012) I have no relevant disclosures to make in connection with this topic.
	# 38 of 47	December 29, 2012 10:46 (EST)
	Carl Adler	abixiban This is not approved for prevention of stroke in a. fib; if people talk about using scientific evidence based medicine then this drug should not be used for this indication; of course if we use medicines off label to help people, which i and other doctors routinely do, because we understand the mechanisms and think it will help them, that is a different matter; that is the art of medicine and not the science; if that is the case then probably my peior recommendations should be followed and not this route; we must use wisdom also; we must remember the rule of Primum Non Nocere and remember these drugs can also harm; we must weigh the risk benefit ratio; in a 91 year old who is presently fine i am not sure the benefit is in using this drug; since she is your mother in law i am assuming heaven forbid there is a bad outcome your wife will not be calling 1-800- sue-the-doctor who used an off label drug; Author's disclosure (Dec 11, 2012) I have no money but will accept voluntary contributions.
	# 39 of 47	December 29, 2012 10:52 (EST)
	Carl Adler	abixiban i see i was wrong - i admit it; it was just approved for a fib ; thought just for coronary intervention; good luck in its use; Mea Culpa; forgive me everyone; Author's disclosure (Dec 11, 2012) I have no money but will accept voluntary contributions.
	# 40 of 47	December 29, 2012 12:50 (EST)
	Leopoldo Piegas	What I did with my mom! Dear Dr. Topol, I have been following your fantastic scientific career since you were a young doctor and came to Sao Paulo in a scientific meeting brought by our common friend Dr. Expedito. My mother a 95 yo active woman had an AF episode followed by a TIA 3 years ago. Since then she is receiving clopidogrel prescribed by her personal cardiologist. I agreed with the prescription despite knowing all the Guidelines recommendations. Very difficult to balance on this age thrombosis vs bleeding. Best regards and Happy 2013! Author's disclosure (Dec 29, 2012) I have no relevant disclosures to make in connection with this topic.
	# 41 of 47	January 5, 2013 01:30 (EST)
	Neshwan Albarwari	The wisdom Salient points 1- The following afternoon she complained that she could not move some of her fingers on her left hand. On exam, it was clear that there was motor difficulty, no sensory loss, and that it was (confined) to the movement of her hand.... this confined transient is unusual for an embolic TIA . The MRI results showed only a small infarct corresponding to her motor deficit, that was transient (<24 hrs) is surprising . Unsure the diagnosis of TIA is secure here . 2- Irrelevant of point 1 , she has intermittent AF with (mildy) dilated LA ( !) despite her age . If you believe in CHA2DSs VASC she Score is 3 which corresponds to a high risk of stroke in atrial fibrillation. Yearly risk of stroke without warfarin treatment is estimated at 3.2%.... so warfarin benefit has to be weighed against risks of bleeding ( which could be fatal) . Plus patient not interested on warfarin Her demography is the highest risk factors for cerebral events and unfortunately is not modifiable . 3- the wisdom here is what has been already siad ''At age 91, is "treatment" really what she would prefer?'' Best wishes, Author's disclosure (Jan 5, 2013) I have no relevant disclosures to make in connection with this topic.
	# 42 of 47	January 5, 2013 08:48 (EST)
	Eddie Vos	In support of the last post -- treatment ? Her opinion as to preference has not been given. How about magnesium adequacy reducing AF as per the current theheart.org/article/1478843.do What is shocking is that this has been known for decades and the chance that a 90 year old gets adequate Mg [half the U.S. population does not], or any [anti-coagulopathy] vitamin is tiny. Author's disclosure (Dec 9, 2012) I have no relevant disclosures to make in connection with this topic.
	# 43 of 47	January 5, 2013 02:32 (EST)
	Neshwan Albarwari	Eddie Vos Do you believe everything you read ? Reducing AF recurrence at 91 I wish Medicine could ! Dr Topol was asking '' whether to use rivaroxaban or apixaban'' . Would stick with apsirin vs warfarin . We know very little about these newbies . Author's disclosure (Jan 5, 2013) I have no relevant disclosures to make in connection with this topic.
	# 44 of 47	January 7, 2013 09:01 (EST)
	D Hackam	CHA2DS2-VASc score is 6 She gets 6 points hypertension (1) age>75 (2) female sex (1) prior stroke/TIA/SEE (2) A CHA2DS2-VASc score of 6 gives one an annualized rate of stroke of 9.8%. Warfarin would reduce that by 70% (and for cardioembolic subtype, by 85%). Apixaban is superior to warfarin even in the face of renal insufficiency (positive statistical interaction for renal*allocation_type in ARISTOTLE) and superior to aspirin even in high bleeding risk situations. I am sure this drug will be marketed soon. ASA is almost useless in AF (at best 19% relative risk reduction, which has probably been overestimated in pre-contemporary era). She does not want warfarin under any circumstances. Given what is available in the US, I would use dabigatran or apixaban. Author's disclosure (Dec 14, 2012) I have no relevant disclosures to make in connection with this topic.
	# 45 of 47	January 9, 2013 02:20 (EST)
	Neshwan Albarwari	D Hackam Good Luck ! Author's disclosure (Jan 5, 2013) I have no relevant disclosures to make in connection with this topic.
	# 46 of 47	January 28, 2013 01:10 (EST)
	Jan Newman	Less is best It appears that the TIA was cardiac in origin, yet I see no echo was done looking for thrombi or assessing C.O. would do at least for baseline. Next while these new generation drugs are "safer" or at least required less monitoring, the patient remains fully anticoagulated which is a problem and risk for hemorrhagic stroke.If you elect to anticoagulate would go with lowest dose and safest drug in elderly. Not warfarin as it remains highly dependent on diet and is frequently not followed closely enough. Order your drugs from Canada. Much cheaper.This decision goes into territory I am unfamilar with as I have not had experience with these drugs. To reduce her episodes of AF I would check her renal function, K+, and MG++ then give her appropriate K+ and MG++ supplementation which have been well documented to reduce the risk of atrial arrhythmias. Give K in non KCL form better tolerated and doesn't lead to acidosis. e.g.K gluconate or citrate. They are generally well tolerated at a dose of 400-800mg MGSO4 or less and 20 meq or less.But would start slowly 10meq and 200mg Mg. Recheck electrolytes after a week or so. Start Mg slowly so you don't run into diarrhea. Aim for a K of 4.0-4.5 and a Mg 1.5-2.5. Low Mg esp common in pt's on thiazide and loop diuretics and not often checked. This combo interesting also lowers blood pressure and may enable her to to on lower doses of antihypertensives and diuretics, improves C.O.and is not used nearly enough. Both Mg and K are OTC and widely available. Can eat bananas for K but they are constipating and dosage is unreliable. Good luck Author's disclosure (Jan 28, 2013) I have no relevant disclosures to make in connection with this topic.
	# 47 of 47	April 3, 2013 10:15 (EDT)
	k bose	I am a new victim of A Fib I had a stent placed in one of my 22 year old vein grafts to Truncus( major marginal branch) three, weeks ago and was left at a dilemma, three anti coagulants, or just two. My cardiologist did not like the new coumadine replacements, as there is difficulty in stopping it in case of bleed. I am a radiologist with considerable interest in Cardiology and interventions. So I am on Coumadine 4 mgr, Second week, Plaxil and ASA, I hope to d/c plaxil in one year. A fib was accidentally discovered just 3 weeks ago! I had a prolonged p-r interval and first degree block since CABG in 1989 No chest pain ever and Thallium scans " normal" x 5 My problem was SOB, which was mishandled for 7 years by 3 cardiologists and 3 Chest men, since all "tests" were NEG( ECGs, Stress echo, Myo. scans) I wish to point out in the case above, it is unlikely her carotids were normal. No one makes it clear re: bleeding is it GI bleed or Cerebral bleed A bleed in brain causes stroke! does it not? Very good discussions, and hard choices with more than one treatment. She is indeed lucky. She may do as well without any of above Rx. My grand mother lived ten years after her stroke to age 96 with hpertension. I live in San Diego and may love to consult Dr Topol. I know of an old Radiology Professor in India that thinks Chelation can cure Cancer and Coronary disease. Author's disclosure (Apr 3, 2013) I have no relevant disclosures to make in connection with this topic.

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