Apple and Johnson and Johnson are collaborating on an interesting research study which aims to analyze the impact of an app-based heart health program with Apple Watch on the early detection of atrial fibrillation (AFib), and the reduction of stroke risk.
I tried to participate in this study but didn’t meet the entry requirements which are as follows:
Be age 65 or older
Be a resident of the United States for the duration of the study
Use an iPhone 6s or later, with iOS 12.2 or later (Learn more)
Have Original Medicare, sometimes called Traditional Medicare (Learn more)
Because I’m still working I have private health insurance and didn’t qualify.
The Heartline Study is a pragmatic, randomized, controlled, virtual research study, from Johnson & Johnson, in collaboration with Apple. The primary objective is to analyze the impact of features on Apple Watch, combined with a heart health engagement program, on early detection of atrial fibrillation and clinical outcomes such as stroke. In addition, the study seeks to determine the impact of a heart health engagement program paired with a medication adherence intervention among those participants receiving an oral anticoagulant therapy who have been previously diagnosed with AFib. The data will also be used to find novel markers to identify, predict, or evaluate other health conditions.
The study website indicates some participants may get to borrow an Apple Watch 5:
Some participants may be asked to obtain an Apple Watch Series 5 or later. These participants will be offered two options to obtain a watch: purchase a watch, or get one on loan for the duration of the study and return it when your participation in the study ends. Johnson & Johnson and Apple are committed to ensuring that participation in the study is not limited based on financial need. Not all participants will be asked to obtain a watch, so make sure to follow the instructions in the app.
Information for Healthcare Providers who are trying to decide whether their patients should participate Is here.
Janssen Scientific Affairs, LLC, an affiliate of Johnson & Johnson, is the sponsor of the Heartline Study. Apple is supporting the study technology and design of the app. Evidation Health provides the technology and study operations that enable the Heartline app and study experience for participants. Best Buy operates the Apple Watch distribution program for eligible study participants.
The ostensible motive for Apple and J and J is to improve outcomes in patients with afib. Obviously Janssen will sell more of its blood thinner Xarelto if more cases of afib are identified.
Participants will be sharing lots of private information with Apple and Evidation.
Despite these concerns I would likely have participated if I qualified and I will recommend that interested patients consider participating in Heartline.
Old habits die hard in medicine. For decades the skeptical cardiologist and his cardiology brethren and sistren have prescribed aspirin to prevent stroke in patients with atrial fibrillation.
For those patients with atrial fibrillation (AF) who were considered low risk it was felt that aspirin provided some benefit in preventing the clots that fly out of the heart (and land in arteries elsewhere in the body) at an acceptably low risk of bleeding. For higher risk patients more powerful and effective agents (oral anticoagulants) are usually recommended.
The American guidelines on AF (2014) gave a IIB recommendation to aspirin. IIB is not a ringing endorsement having been described as “this is our suggestion, but you may want to think about it.”
For patients with nonvalvular AF and a CHA2DS2-VASc score of 1, no antithrombotic therapy or treatment with an oral anticoagulant (OAC) or aspirin may be considered. (Level of Evidence: C)*
Thus, in the 2016 European guidelines on the management of AF the authors state that “the evidence supporting antiplatelet mono therapy (e.g. aspirin or clopidogrel) for stroke prevention in AF is very limited” and the bleeding rate” is similar to OAC”:
Aspirin and other antiplatelets have no role in stroke prevention (III A). The combination of anticoagulation with antiplatelets increases bleeding risk and is only justified in selected patients for a short period of time; for example, in patients with an acute coronary syndrome or stent, balancing the risk of bleeding, stroke and myocardial ischaemia (IIa B/C).
Stroke risk evaluation is based on the CHADS-VASc score. With a score ≥2 in male and ≥3 in female patients, anticoagulation for stroke prevention is clearly recommended, while in a score of 1 in males and 2 in females, anticoagulation should be considered. No antithrombotic therapy of any kind should be prescribed in patients with a CHADS-VASc score of 0 (males) or 1 (females).
Antiplatelet therapy increases bleeding risk, especially dual antiplatelet therapy (2.0% vs. 1.3% with antiplatelet monotherapy; P < 0.001), with bleeding rates that are similar to those on OAC. Thus, antiplatelet therapy cannot be recommended for stroke prevention in AF patients.
“The European guidelines have done away with aspirin for stroke prevention in atrial fibrillation. It barely made it into our current US guidelines. I don’t think aspirin should be in there and I don’t think it will be there in the next guidelines. The role of aspirin will fall away,” said Bernard J. Gersh, MB, ChB, DPhil, Professor of Medicine at the Mayo Clinic in Rochester, Minnesota. “It’s not that aspirin is less effective than the oral anticoagulants, it’s that there’s no role for it. There are no good data to support aspirin in the prevention of stroke in atrial fibrillation.”
“The use of aspirin has probably been misguided, based upon a single trial which showed a profound effect and was probably just an anomaly,” said N.A. Mark Estes III, MD, Professor of Medicine and Director of the New England Cardiac Arrhythmia Center at Tufts University in Boston, and a past president of the Heart Rhythm Society
I would just take it off of your clinical armamentarium because the best available data indicate that it doesn’t prevent strokes. I’m certainly not using it in my patients. Increasingly in my patients with a CHA2DS2-VASc of 1, I’m discussing the risks and benefits of a novel oral anticoagulant,” said Dr. Estes.
Those are amazingly definitive statements. But, as I’ve learned we can’t just except what the “experts” and the guidelines tell us we have to look at the original studies informing these decisions.
It compared warfarin (measured by PT ratio) to placebo and aspirin 325 mg to placebo in preventing stroke in AF patients. Warfarin reduced stroke by 67% and aspirin by 42%. The risk of significant bleeding was similar at around 1.5% per year for all three arms.
Based on this and other AF trials (AFASAK, CAFA, SPINAF, EAFT, et al. ) when I gave talks or taught cardiology fellows in the 1990s my message (similar to this presentation) emphasized the superior benefits of warfarin compared to aspirin (especially when monitored by INR in a 2.0 to 3.0 range) in higher risk AF patients. Overall it was felt that aspirin (dosing varying from 100 to 325 mg) reduced stroke/embolism by 20-30% compared to placebo and would offer benefit to those patients at low risk or who could not tolerate warfarin.
Based on the 2014 American guidelines (and a focused update in 2019 which did not address this issue) I had not been actively taking my low risk patients off baby aspirin.
I was prompted to re-research this question and write this post because a 58 year old woman with paroxysmal AF and hypertension called the office today asking if I wanted her to take a baby aspirin daily. She has a CHADS2VASC score of 2 (woman and hypertension) and falls into the category where we should have an in depth conversation about the risks and benefits of anticoagulant therapy.
I have that discussion with her each visit and thus far we’ve decided to hold off on starting an anticoagulant drug like Eliquis. She has promised to record her ECG daily (using her Kardia Mobile ECG device) and report any onset of AF. If AF recurs we will have another discussion about Eliquis.
I spent several hours pouring over the original studies and more recent studies, reviews and meta-analyses and reached the following conclusions:
With the advent of the newer oral anticoagulants (NOACs) in the last decade which offer better stroke reduction and less bleeding than warfarin patient-physician discussions should be about taking a NOAC or not. Aspirin should not be considered as a lower risk/effective alternative as its benefits are minimal and bleeding risks similar to NOACs.
I told my patient no on the daily baby aspirin and from now on I will recommend stopping aspirin (assuming no other reason to be on it) to all my low risk AF patients.
The components of the stroke risk score- CHA2DS2-VASc = Congestive Heart failure, hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65–74, and Sex (female);
For those interested in a discussion on why females get a point in the risk score but a different cut-off for OAC therapy this is from the ESC guidelines:
Many risk factors contribute to the increased risk of stroke in patients with AF as expressed in the CHA2DS2-VASc score. The evidence for female sex as a risk factor has been assessed in many studies. Most studies support the finding that females with AF are at increased risk of stroke. One meta-analysis found a 1.31-fold (95% CI: 1.18–1.46) elevated risk of stroke in females with AF, with the risk appearing greatest for females ≥75 years of age (S4.1.1-35). Recent studies have suggested that female sex, in the absence of other AF risk factors (CHA2DS2-VASc score of 0 in males and 1 in females), carries a low stroke risk that is similar to males. The excess risk for females was especially evident among those with ≥2 non–sex-related stroke risk factors; thus, female sex is a risk modifier and is age dependent (S4.1.1-49). Adding female sex to the CHA2DS2-VASc score matters for age >65 years or ≥2 non–sex-related stroke risk factors
If you’re curious what constitutes a IIB recommendation it is described in the yellow box below My best summary is still “not a ringing endorsement”.
If you want to see the ESC guideline recommendations in detail
The wide-spread public conception that catheter ablation cures atrial fibrillation and reduces one’s risk of stroke or dying has fueled a $4.5 billion industry. Until very recently there were no published randomized trials supporting this expensive and risky procedure.
The recently published landmark CABANA trial found that in patients with afib “the strategy of catheter ablation, compared with medical therapy, did not significantly reduce the primary composite end point of death, disabling stroke, serious bleeding, or cardiac arrest. ”
So there is no proven benefit of ablation on death, stroke, bleeding or cardiac arrest. This means that a medical management approach to management of afib is always an acceptable approach. Especially an enlightened medical approach.
In CABANA, women and those patients >75 years of age did worse with ablation as this chart shows.
What about complications? I mentioned that ablation was risky and this is because any time you put a catheter in someone’s heart you can create life-threatening problems. When you then heat up the tip of that catheter it is possible to burn/damage/destroy things that are not your target.
A reassuring finding of CABANA was that ablation did not do worse than drugs. But one of the messages I heard from HRS was that CABANA showed that AF ablation is safe. This is a problem.
The complications in the ablation arm were more serious and more numerous than those in the drug arm. We will have to wait for the published paper for formal comparisons. CABANA likely represents a best-case scenario because it allowed only experienced operators and centers to be part of the trial. Many people undergo ablation by less experienced operators.
Another important safety issue is the asymmetry of procedural complications. When you talk privately with ablation doctors, many, perhaps most, relay the story of a tragic death of an otherwise healthy middle-aged adult from an atrial-esophageal fistula.
Yes. A well-recognized and highly feared complication of ablation , atrial-esophageal fistula, causes rapid death due to exsanguination through a channel between the left atrium and the esophagus which develop due to destruction/burning of the normal esophageal/atrial tissue.
In this chart taken from the CABANA abstract presentation you can see the complications which do not include a highly feared atrial-esophageal fistula.
Can Catheter Ablation Improve Quality of Life?
Basically, after the CABANA trial we have no evidence that ablation will improve hard outcomes in afib patients. However, there are numerous patients who feel they have greatly benefited from the procedure, experiencing years of afib free existence.
This benefit of ablation, of improving quality of life and making patients feel better is important.
The CABANA trial also looked at quality of life and in part II of this article I’ll examine that in detail.
Update 6/12/2019 357 PM.
Twitter follower @mrice5025 was kind of enough to read the above closely enough to realize that the number of atrial esophageal fistulae was actually zero in the CABANA trial and I have corrected the text accordingly.
I have seen a case of this mostly fatal complication in a patient who had an ablation done at an outside hospital 5 weeks earlier and who rapidly died from it and I try to be very aware of its possibility as early diagnosis and surgery is the key to survival.
AF ablation carries a small risk of complications with the most serious being atrioesophageal fistula (AEF). Although the incidence is less than 0.1%, it is usually fatal Esophageal perforation or fistula was reported in 31 patients (0.016%) in the Global Survey of Esophageal and Gastric Injury in Atrial Fibrillation study. Symptom onset for esophageal perforation or fistula was reported on average 19.3 days after the ablation procedure but could appear as short as 6 days and as long as 59 days post ablation.Esophageal injury has been observed most frequently with percutaneous radiofrequency ablation, although it has also been reported with other energy sources including cryoablation,high-intensity focused ultrasound and even surgical ablation.
The featured image comes from this Cleveland Clinic video which has some great graphics and reasonable information (once you get by the annoying lady at the beginning who describes ablation as “an excellent minimally invasive” procedure.)
At my hospital, St. Luke’s, I have three outstanding electrophysiologists who do excellent ablations,, Jonas Cooper, Cary Fredman, and Mauricio Sanchez.
The results of the Apple Heart Study, were presented this morning at the American College of Cardiology Scientific Sessions amid intense media scrutiny. The AHS is a “prospective, single arm pragmatic study” which had the primary objective of measuring the proportion of participants with an irregular pulse detected by the Apple Watch who turn out to have atrial fibrillation on subsequent ambulatory ECG patch monitoring.
I and over 400,000 other Apple Watch owners participated in the AH study by downloading the Apple Heart Study app and self-verifying our eligibility.
My assessment is that we have learned little to nothing from the AHS that we didn’t already know. I’m also concerned that many patients suffered anxiety or unnecessary testing after being referred to urgent care centers, emergency departments, cardiologists or primary care providers and the results of these inappropriate referrals may never be determined.
Here is the study in a nutshell:
Participants enrolled by submitting information using the iPhone Heart Study app and none of their isubmitted nformation was verified.
An irregular pulse notification was issued to 0.5% of participants who were then contacted and asked to participate in a Telehealth visit with a doctor (who we will call Dr. Appleseed)
Only 945 of the 2161 who received a pulse notification participated in the first study visit.
Interestingly, Dr. Appleseed was empowered to send participants to the ER if they had symptoms (chest pain, shortness of breath, fainting/losing consciousness) It is not clear how many were sent to the ER and what their outcomes were but this flow diagram shows that 20 were excluded from further testing due to “emergent symptoms.”
Another 174 participants were excluded after finding out at the first visit that they had a history of afib or aflutter and 90 due to current anticoagulant use (both of these factors were exclusion criteria which gives us an idea of how accurate the information was at the time of participant entry.)
After all these exclusions only 658 ECG monitor patches were shipped to the participants of which only 450 were returned and analyzed.
This means of the original 2161 participants who were notified of pulse irregularity, the study only reports data on 450 or 21%. Such a low rate of participation makes any conclusions from the study suspect.
Of the 450 ECG patches analyzed only 34% were classified as having afib. Only 25% of this afib lasted longer than 24 hours.
After the patch data was analyzed, patients had a second Telehealth visit with Dr. Appleseed who reviewed the findings with the patient. Per the initial published description of the methods of the AHS (see here) Dr. Appleseed would tell the participant to head to the ER if certain abnormalities were found on the ECG.
Per the study description (apple heart study), Dr. Appleseed recommended a visit to the PCP for “AF or any other arrhythmia” detected by the patch:”
“If AF or any other arrhythmias have been detected in reviewing the ambulatory ECG monitor data, or if there are other non-urgent symptom identified by the study physician during the video visit that may need further clinical evaluation, the Study Telehealth Provider directs the participant to his or her primary health care provider”
At this point it seems likely that a lot of participants were instructed to go see their PCPs. Because as someone who looks at a lot of 2 week ambulatory ECG recordings I know that is the rare recording that does not show “other arrhythmias.”
Even more distressing is the call that participants would have received based on “the initial technical read:” I’m presuming this “technical read” was by a technician and not by a cardiologist. In my experience, many initial reads from long term monitors are inaccurate.
“If the initial technical read identifies abnormalities that require urgent attention (ventricular tachycardia or ventricular fibrillation, high-degree heart block, long pauses, or sustained and very rapid ventricular rates), then the participant is contacted immediately and directed to local emergency care or advised how to seek local emergency care.”
I wonder how many ERs had AHS participants show up saying they had been told they had a life-threatening arrhythmia? How much down stream testing with possible invasive, life-threatening procedures such as cardiac catheterization were performed in response to these notifications?
Overall, these findings add nothing to previous studies using wearable PPG technology and they certainly don’t leave me with any confidence that the Apple Watch is accurately automatically detecting atrial fibrillation.
Was more harm than good done by the Apple Heart Study?
We will never know. The strength of this study, the large number of easily recruited participants is also its Achilles heel. We don’t know that any information about the participants is correct and we don’t have any validated follow up of the outcomes. In particular, I’m concerned that we don’t know what happened to all of these individuals who were sent to various health care providers thinking there might be something seriously wrong.
Perhaps Apple and Stanford need to review the first dictum of medicine: Primum Non Nocere, First Do No Harm.
Messerli and Bangalore use a second figure to graphically illustrate the potential consequences of the differing guidelines.
Cardiovascular death rates thus may vary three-fold depending on what BP goal we choose.
This marked variation in treatment recommendation highlights that they
are not only an evaluation and interpretation of evidence in question, but also a judgment weighted by personal, regulatory, and organizational preferences that can vary from physician to physician within a country and across geographical regions.
Physicians and patients (hopefully through shared decision making) are going to have to do some thinking on their own.
Messerli and Bangalore quote Immanuel Kant in this regard:
Enlightenment is man’s emergence from his self-imposed nonage. Nonage is the inability to use one’s own understanding without another’s guidance. This nonage is self-imposed if its cause lies not in lack of understanding but in indecision and lack of courage to use one’s own mind without another’s guidance. Dare to know! (Sapere aude.) “Have the courage to use your own understanding,” is therefore the motto of the enlightenment.
As a 64 year old who has emerged from his nonage with hypertension, I have carefully examined the latest American hypertension guidelines especially in light of the SPRINT study and elected to add a third anti-hypertensive agent to get my average BP below 130/80. It’s worked for me with minimal side effects but I carefully monitor my BP.
If I notice any symptoms (light-headed, fatigued) suggesting hypotension associated with systolic BP <120 mm Hg I tweak my medical regimen to allow a higher BP.
Like all of my patients I would prefer to be on less medications, not more but when it comes to enlightenment about the effects of hypertension, it is now clear that lower is better for most of us in our sixties down to at least 130/80*.
Sapere Audaciously Yours,
*N.B. In the SPRINT study the BP was obtained using an automatic BP cuff after 5 minutes of rest with the patient unobserved and averaging 3 recordings one minute apart.
This “research grade BP” averages about 12 mm Hg less than a routine single clinic obtained BP (see here.)
The skeptical cardiologist recently asked his Eternal Fiancée to grab a bottle of baby aspirin while she was at the local Walgreen’s. Aspirin or acetyl salicylic acid (ASA) comes in either a 325 mg dose or in a low dose which can be between 75 to 100 mg and is often called “baby” aspirin.
However, since a link between aspirin use and a potentially lethal disease called Reye’s syndrome was identified in the 1980s, no authorities recommend aspirin in children or babies, and the low dose ASA (LDASA) is primarily marketed and used for prevention of cardiovascular disease.
Although Bayer and Dr. Oz would have us believe that all individuals over the age of 55 should be taking LDASA, as I pointed out here in 2014, the FDA no longer recommends it for prevention of cardiovascular disease.
The USPSTF recommends initiating low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer (CRC) in adults aged 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years.
I’m 63 years old, so the USPTF recommendation for me to take LDASA is a little less enthusiastic:
The decision to initiate low-dose aspirin use for the primary prevention of CVD and CRC in adults aged 60 to 69 years who have a 10% or greater 10-year CVD risk should be an individual one. Persons who are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years are more likely to benefit. Persons who place a higher value on the potential benefits than the potential harms may choose to initiate low-dose aspirin.
Following my own advice (see here), I have started taking 81mg of aspirin regularly (well, when I remember) in order to prevent stroke and heart attack. I do have subclinical atherosclerosis with a plaque in my LAD, and I think the aspirin will make my platelets less sticky and less likely to form clots if my plaque ruptures, thereby reducing my chances of an acute heart attack.
I am willing to accept the increased risk of bleeding from the gastrointestinal tract and hemorrhagic stroke associated with LDASA use.
Previous to this I had been taking ASA from little sample bottles that Bayer sends to my office. These bottles are quite annoying as they are stuffed with cotton and contain very few pills making extrication of the tiny pills an exercise in futility (I am using this as an excuse for my lack of regularity in taking them).
There’s no reason to pay the premium for Bayer ASA despite the company’s advertising attempts to link inextricably their name with ASA. Aspirin is aspirin, whether Bayer made it or Walgreens. In Bayer’s defense, their website has reasonable information on heart attacks and they appear to be giving aspirin away to people named Smith.
But what type of aspirin should you get? Enteric-coated, safety-coated, delayed release, chewable?
I asked the Eternal Fiancée to buy the cheapest baby aspirin possible.
She ended up buying a chewable formulation with orange flavoring, presumably aimed at children:
When I put one of these in my mouth I tasted the sickly sweet taste of an artificial sweetener. The ingredients are listed as: Dextrates, Ethyl Cellulose, FD&C Yellow 6 Aluminum Lake, Orange Flavor, Sodium Saccharin, Starch. Saccharine! Yikes!
The only reason to chew ASA is if you are having an acute heart attack.
In this situation, chew 4 of the LDASA or one regular 325 mg aspirin. Chewing the aspirin makes the levels rise faster in your blood stream and can help dissolve the clot causing your heart attack more rapidly.
How do you know if you are having a heart attack? This is actually a very difficult question to answer with certainty. See here for a reasonable discussion.
Low Dose Aspirin: Enteric-Coated versus Non-coated
It is very difficult (perhaps impossible) to find low dose, non-chewable ASA that has not been “safety-coated” or “enteric-coated.” These formulations have become popular by promoting the idea that they are less likely to cause stomach pain or bleeding.
The concept is that the coating leads to delaying the aborption of the ASA until it reaches the small intestines where, presumably, it will do less damage. However, there is no good evidence to support lower bleeding risk with enteric-coasted (EC) ASA.
There is, on the other hand, very good evidence that therapeutic levels of aspirin in the bloodstream, and therefore the speed and efficacy of ASA in preventing heart attacks, is reduced by these “safety” formulations.
Volunteers were given either 325mg regular ASA or 325mg EC ASA and researchers looked at how each formulation effected platelet activity. The onset of antiplatelet activity was determined by the rate and extent of inhibition of serum thromboxane B2(TXB2) generation.
The EC ASA took longer and was less effective at blocking platelet activity than plain ASA. Presumably, this translates into lower efficacy in preventing heart attacks and strokes.
Therefore, if you feel like you are having a heart attack, chew ASA which is not enteric or safety-coated. Yes, you can chew a regular 325 mg ASA pill. Or you can chew 4 of the LDASA, preferably uncoated but still helpful if coated.
If it turns out you weren’t having a heart attack there is no down side to having chewed 325 mg ASA.
I just spent a fair amount of time trying to find non EC, non-chewable LDASA online and failed.
For the time being I will be swallowing daily the orange chewable LDASA and I will carry a bottle around in my satchel for emergency use.
N.B. Aspirin is generally recommended in secondary prevention of cardiovascular disease, ie. for those who have had heart attacks, stents or bypass surgery . For a good review of the evidence for this see here.
The most serious adverse consequence of having atrial fibrillation is stroke. Since we have safe and effective ways of preventing afib-related stroke with oral anticoagulant drugs (blood thinners), a major decision for the newly diagnosed patient with atrial fibrillation is “should I take a blood thinner?”
To answer this question the afibber should engage in a lengthy discussion with his/her health-care provider which results in a shared and informed decision. Such discussion must cover your risk of stroke, the benefits of blood thinners in preventing stroke, the bleeding risks of blood thinners and the pros and cons of the five oral anticoagulants available to prevent stroke.
Estimating Your Risk of Stroke With Afib
The best way we have of estimating a patient’s risk of stroke if they have atrial fibrillation (AF) is by the CHA2DS2-VASc scale (which I like to call the Lip scale)
This scale take the factors we know that increase the risk of stroke and assigns 1 or 2 points. The acronym comes from the first letter of the factors that are known to increase risk as listed to the left.
Most of the factors get 1 point, but prior stroke (S) and age>75 (A) get 2 points.
We then add up your points and use another chart (or app) to calculate the risk of stroke per year.
Your risk of stroke is very low if you have zero risk factors; it gets progressively higher as you reach the maximum number of 9.
Treatment with an oral anticoagulant (OAC), either warfarin, or one of the four novel anticoagulant agents (NOACS), is recommended when score is >/=2 corresponding to a risk of stroke above 1-2% per year.
These blood thinners have consistently been shown to lower your risk of stroke or systemic embolization (when a clot from the heart goes somewhere other than the brain) by almost 70%.
The higher the risk, the more the benefit of these blood thinners in preventing stroke.
Both European and American guidelines recommend using the CHA2DS2-VASc score for initial risk stratification. The European guideline recommends OAC therapy for males with a CHA2DS2-VASc score ≥1 and for female patients with a score ≥2., whereas the American guideline recommends use of OAC if the CHA2DS2-VASc score is ≥2 for men and women.
I’ve been using the CHA2DS2-VASc scale for several years in my afib patients. I try to review the patient’s risk of stroke and their risk of bleeding during every office visit, and decide whether they should be on or off an OAC.
Bleeding From Blood Thinners
All OACs cause increase bleeding. They don’t discriminate between bad clots that cause strokes and good clots that stop you from bleeding.
If you’re taking one you are more likely to have nose bleeds, bleeding into the intesitnal tract or urine and you will bleed longer when cut and more profusely if in an accident. In lower stroke risk patients, the bleeding risk of OAC of 1% per year may outweigh the benefits conferred by stroke reduction.
I wrote a post entitled “Why Does The TV Tell me Xarelto Is a Bad Drug” which points out that law suits against the makers of the newer OACs are frivolous and that these NOACs are likely more safe and effective than warfarin.
In recent years, four new drugs for reducing strokes in patients with atrial fibrillation which are much less influenced by diet and medications have gained approval from the FDA. These are generally referred to as “novel anticoagulants” reflecting their newness, different effects from warfarin or aspirin, and their blood thinning properties. The first (brand name Pradaxa) was released to much excitement and fanfare in October, 2010. The press release for this approval read as follows:
PRADAXA, an oral direct thrombin inhibitor2 that was discovered and developed by Boehringer Ingelheim, is the first new oral anticoagulant approved in the U.S. in more than 50 years. As demonstrated in the RE-LY® trial, PRADAXA 150mg taken twice daily has been shown to significantly reduce stroke and systemic embolism by 35 percent beyond the reduction achieved with warfarin, the current standard of care for patients with non-valvular atrial fibrillation. PRADAXA 150mg taken twice daily significantly reduced both ischemic and hemorrhagic strokes compared to warfarin
What was very clear from the study with Pradaxa and stated very clearly in all publications and patient and doctor information sources was that just like warfarin, patients could have severe bleeding complications, sometimes fatal. Overall serious bleeding complications were about the same (the rate of major bleeding in patients Pradaxa in the RE-LY trial was 3.1% versus 3.4% in the warfarin group) but Pradaxa had about 50% more bleeding from the gastrointestinal tract and warfarin about 50% more bleeding into the brain.
Another big difference between the novel anticoagulants and warfarin is that we have antidotes (Vitamin K, fresh frozen plasma) that can reverse the anticoagulation state rapidly for warfarin but until recently none for the newer drugs. (There is now available an antidote for Pradaxa). This information also was made very clear to all doctors prescribing the medications in the package insert and educational talks. Despite this, in the major trials comparing these newer agents to warfarin, the newer agents were as safe or safer than warfarin.
The most feared bleeding complication on all OACs is bleeding into the head (intracranial hemorrhage). The risk of ICH is between 0.2 to 0.4 percent per year on warfarin. Studies show with the NOACs the risk is about half of the risk on warfarin.
Should You Take a NOAC or Warfarin?
Once the decision has been made to start a blood thinner, the next question is whether to take warfarin or a NOAC. Warfarin (brand name Coumadin) has been utilized since the 1950s and prior to 2010 was the only drug available for doctors to reduce clot formation in the heart and susbsequent strokes.. Warfarin is only effective and safe within a narrow window and its effects are strongly influenced by Vitamin K in the diet and most medications. Thus, frequent blood testing and adjustment in dosage is needed, and close monitoring of diet and changes in medications. Even with this close monitoring, serious and sometimes fatal bleeding occurs frequently with warfarin.
Here is a patient information sheet on warfarin which gives you an idea of issues you will need to be aware of when taking the drug. (WArfar patient handout)
If you do a Google search on warfarin you will quickly discover that it is used as a rat poison. Scientists isolate the chemical from sweet clover that was causing cows to bleed and then developed a more potent form that they named warfarin in the 1940s. After developing blood tests that allowed the drug to be used safely to dissolve clots it was approved for human use in the 1950s.
Warfarin or more potent variations on its chemical structure have been utilized as rat poison since the 1940s.
The rats are consuming much larger quantities of the blood thinner and are clearly not being monitored for blood thinness.
Some despicable sites peddling alternative or natural products such as this “Healthy Habits” site engage in fear-mongering over the warfarin/rat poison connection in order to promote totally unproven products. Healthy Habits indirectly suggests that Nattokinase : is a safer, more effective natural alternative to warfarin” This remarkable enzyme has the ability to dissolve blood harmful clots involved in heart disease and strokes without upsetting normal healthy clotting.”
Such misinformation is dangerous and could lead to patients stopping a life-saving medication and suffering a stroke.
By the way, in this Xarelto (another NOAC competitor) ad, Kevin Nealon says he chose Xarelto over warfarin because he wanted to eat salads. This is a common misconception and the makers of Xarelto should be ashamed for promulgating it.
I tell my patients it is fine to eat green, leafy vegetables while taking warfarin. The Vitamin K in the vegetables does influence the effectiveness of warfarin thinning blood but this is why we check the blood test to determine the appropriate dosage of warfarin for you and your personal dietary Vitamin K consumption , be it high or low.
Novel Oral Anticoagulant Drugs
The newer OACs, in contrast to warfarin do not require blood tests for monitoring of their efficacy because their levels are not significantly influenced by changes in diet or most medications.
In head to head studies versus warfarin four of these NOACs have demonstrated at least similar efficacy in preventing stroke and at most similar bleeding risk.
Due to their perceived advantages most new prescriptions for OACs are for NOACs. In contrast to 2014 American afib guidelines which don’t state a preference, the most recent European afib guidelines recommend choosing a NOAC over warfarin when initiating anticoagulant therapy in patients who are eligible for NOACs. (Ineligible patients include those with mitral stenosis, mechanical heart valves and end-stage renal disease.)
The ESC guidelines published in 2016, , make choosing a NOAC over warfarin a IA recommendation. This means there is a consensus that the treatment should be recommended (Class I recommendation) and that there is strong evidence from randomized controlled trials to support it (Level A.)
I have decided to primarily use Eliquis (apixaban) as my NOAC of choice based on my comparison of the different NOAC studies. If a patient’s insurance covers another NOAC better , making it cheaper then I am happy to switch.
Because these four NOACs are new and brand name they are significantly more expensive than warfarin. Cost varies substantially based on type of insurance coverage and we can only determine how much a patient will pay for any given NOAC based on writing a prescription and having a pharmacy check out the cost.
I have found some patients paying nothing for their NOAC whereas some are paying several hundred dollars monthly. The more NOACs cost, the more likely the patient and I are to choose warfarin.
While waiting to determine if cost is going to be prohibitive I will typically provide the patient with samples of the NOAC chosen. The pharmaceutical companies making these NOACs are clearly making substantial profits off them and they are happy to provide lots of samples to doctors to influence the doctors to utilize their product.
NOACs are being extensively promoted both to physicians and directly to patients. Physicians have to be especially careful to make sure they are presenting a true summary of the relative risks and benefits of warfarin versus NOACs in light of these constant attempts to influence them.
Despite now having four NOACs with similar benefits and ease of use compared to warfarin, the cost of these agents doesn’t seem to have declined significantly from when the first NOAC came on the market. Personally, I would love to see Medicare step in and negotiate significantly lower costs for American senior citizens.
An abstract at the ACC meeting in March of 2017 suggested a reduction in medical costs with NOACs despite their high costs. This was related to a lower rate of major bleeding complications: Xarelto cost $542 per patient compared with warfarin’s $500, or $42 more. Pradaxa, cost $367 to warfarin’s $452, saving $85. Eliquis cost $286 charge against warfarin’s $537 resulting in $251 in savings. Data were from from a study of U.S. Medicare patient records.
Aspirin May Not Prevent Stroke In Afib
Many patients consider aspirin to be a “blood thinner” that has some benefit in preventing clots and strokes in patients with afib. However, aspirin is not considered a blood thinner or anticoagulant and is more properly termed an anti-platelet agent.
I used to consider aspirin at doses of 120 to 200 mg daily provided some protection against stroke in afib and put afib patients on aspirin who were low risk for stroke or would not or could not take OACs.
More and more, however, experts are reaching the conclusion that the substantial bleeding complications from aspirin usage outweigh its very slight benefit in stroke prevention.
The most recent ESC guidelines, in fact, list aspirin therapy for stroke prevention in atrial fibrillation as IIIA. That means that overall it is felt to be harmful (III) with a high level of evidence (A.)
Bleeding risks for aspirin are similar to warfarin and Eliquis. Thus, patients should not consider aspirin as a safer alternative to prevent stroke in afib.
Finally, do not take any “natural” supplement that has been promoted as a blood thinner. These are neither safe nor effective. Remember that it took years of scientific investigation and careful testing in animals then humans before warfarin (the agent in sweet clover that caused cows to bleed ) was transformed into a safe and effective anticoagulant.
The skeptical cardiologist received an email from a woman telling him that September is atrial fibrillation awareness month and offering me the free use of an infographic given that I
“care deeply about helping people living with AF.”
Well, I do care about deeply about people living with atrial fibrillation and pretty much all cardiac diseases (except perhaps Schuckenbuss syndrome.)
That’s the major reason I write this blog. I’ve written a lot about Afib and have a lot more i want to write (I really want to write about antiarrhythmic drugs, i.e. drugs that maintain you in normal sinus rhythm.)
But I don’t find it particularly helpful to assign a disease to a month or a day so my posts on atrial fibrillation come out randomly dependent on the mysterious machinations of my messy mind.
It turns out that September, 2009 was declared National Atrial Fibrillation Awareness Month (NAFAM) by Senate Resolution 262 although Stop Afib.org wants us to believe September is eternally NAFAM.
However, the email prompted me to better organize my atrial fibrillation and stroke page (now containing all that I have written on the subjects) which I have copied below.
Foxglove Equipoise. When William Withering began treating patients suffering from dropsy in 1775 with various preparations of the foxglove plant he wasn’t sure if he would help or hurt them. After 240 years of treatment, we are still unsure if the drug obtained from foxglove is useful.
Why Does the TV Tell Me Xarelto Is A BAD Drug? Anticoagulant drugs that prevent the bad clots that cause stroke also increase bleeding risk. A bleeding complication is not a valid reason to sue the manufacturer. The lawsuit are strictly a money-making tactic for sleazy lawyers.
Are infographics really helpful? Someone should do a study on that. Perhaps we could use the money we spend on infographics in atrial fibrillation to research whether the left atrial appendage should be excised at the drop of a hat.
Here’s the infographic (because everyone loves an infographic!)
The first part lays out the problem of AF with patriotic bunting.
The second part uses the annoying numerical infographic approach.
The third part explains why I got the email. A product is being promoted. The woman who sent me the email works for MyTherapyApp.
The skeptical cardiologist has been testing the comparative accuracy of two hand-held mobile ECG devices in his office over the last month. I’ve written extensively about my experience with the AliveCor/Kardia (ACK) device here and here. Most recently I described my experience with the Afib Alert (AA) device here.
Over several days I had my office patients utilize both devices to record their cardiac rhythm and I compared the device diagnosis to the patient’s true cardiac rhythm.
In 14 patients both devices correctly identified normal sinus rhythm. AFA does this by displaying a green check mark , ACK by displaying the actual recording on a smartphone screen along with the word Normal.
The AFA ECG can subsequently uploaded via USB connection to a PC and reviewed in PDF format. The ACK PDF can be viewed instantaneously and saved or emailed as PDF.
Normal by AFA/Unreadable or Unclassified by AliveCor
In 5 patients in normal rhythm (NSR) , AFA correctly identified the rhythm but ACK was either unreadable (3) or unclassified (2). In the not infrequent case of a poor ACK tracing I will spend extra time adjusting the patient’s hand position on the electrodes or stabilizing the hands. With AFA this is rarely necessary.
In this 70 year old man the AFA device recording was very good and the device immediately identified the rhythm as normal.
ACK recording was good quality but its algorithm could not classify the rhythm.
A 68 year old man who had had bypass surgery and aortic valve replacement had a very good quality AFA recording with correct classification as NSR
AliveCor/Kardia recordings on the same patient despite considerable and prolonged efforts to improve the recording were poor and were classified as “unreadable”
There were 3 cases were AFA diagnosed atrial fibrillation (AF) and the rhythm was not AF. These are considered false positives and can lead to unncessary concern when the device is being used by patients at home. In 2 of these ACK was unreadable or unclassified and in one ACK also diagnosed AF.
A 90 year old woman with right bundle branch block (RBBBin NSR was classified by AFA as being in AF.
The ACK algorithm is clearly more conservative than AA. The ACK manual states:
If you have been diagnosed with a condition that affects the shape of your EKG (e.g., intraventricular conduction delay, left or right bundle branch block,Wolff-Parkinson-White Syndrome, etc.), experience a large number of premature ventricular or atrial contractions (PVC and PAC), are experiencing an arrhythmia, or took a poor quality recording it is unlikely that you will be notified that your EKG is normal.
One man’s rhythm confounded both AFA and AC. This gentleman has had atrial flutter in the past and records at home his rhythm daily using his own AliveCor device which he uses in conjunction with an iPad.
During our office visits we review the recordings he has made. He was quite bothered by the fact that he had several that were identified by Alivecor as AF but in fact were normal.
A recording he made on May 2nd at 845 pm was read as unclassified but with a heart rate of 149 BPM. The rhythm is actually atrial flutter with 2:1 block.
Sure enough, when I recorded his rhythm with ACK although NSR (with APCS) it was read as unclassified
AFA classified Lawrence’s rhythm as AF when it was in fact normal sinus with APCs.
One patient a 50 year old woman who has a chronic sinus tachycardia and typically has a heart rate in the 130s, both devices failed.
We could have anticipated that AC would make her unclassified due to a HR over 100 worse than unclassified the tracing obtained on her by AC (on the right)was terrible and unreadable until the last few seconds. On the other hand the AFA tracing was rock solid throughout and clearly shows p waves and a regular tachycardia. For unclear reasons, however the AFA device diagnosed this as AF.
Accuracy in Patients In Atrial Fibrillation
In 2/4 patients with AF, both devices correctly classified the rhythm..
In one patient AFA correctly diagnosed AF whereas ACK called it unclassified.
This patient was in afib with HR over 100. AFA correctly identified it whereas ACK called in unclassified. The AC was noisy in the beginning but towards the end one can clearly diagnose AF
In one 90 year old man AFA could not make the diagnosis (yellow)
ACK correctly identified the rhythm as AF
One patient who I had recently cardioverted from AF was the only false positive ACK. AliveCor tracing is poor quality and was called AF whereas AFA correctly identified NSR>
The sensitivity of both devices for detecting atrial fibrillation was 75%.
The specificity of AFA was 86% and that of ACK was 88%.
ACK was unreadable or unclassified 5/26 times or 19% of the time.
The sensitivity and specificity I’m reporting is less than reported in other studies but I think it represents more real world experience with these types of devices.
In a head to head comparison of AFA and ACK mobile ECG devices I found
-Recordings using AfibAlert are usually superior in quality to AliveCor tracings with a minimum of need for adjustment of hand position and instruction.
-This superiority of ease of use and quality mean almost all AfibAlert tracings are interpreted whereas 19% of AliveCor tracings are either unclassified or unreadable.
-Sensitivity is similar. Both devices are highly likely to properly detect and identify atrial fibrillation when it occurs.
-AliveCor specificity is superior to AfibAlert. This means less cases that are not AF will be classified as AF by AliveCor compared to AfibAlert. This is due to a more conservative algorithm in AliveCor which rejects wide QRS complexes, frequent extra-systoles.
Both companies are actively tweaking their algorithms and software to improve real world accuracy and improve user experience but what I report reflects what a patient at home or a physician in office can reasonably expect from these devices right now.
I’m writing this brief post as a warning to any individuals who have purchased the smartphone app AF Detect (screen shot below from Apple app store.) It is not a reliable detector of atrial fibrillation (AF).
A patient of mine with AF recently purchased this app unbeknownst to me. He relied on its faulty information which reassured hm he was not in AF when in fact he was in AF. Such misinformation has the potential to lead to dangerous delays in diagnosis.
There are multiple reviews on the Apple and Google app sites which confirm the total lack of reliability of this app to diagnose AF with multiple instances of both failure to detect known AF and inappropriate diagnosis of AF when rhythm was not AF.
In the description of the app the company says the app will “transform you rmobile device into a personal heart rate monitor and atrial fibrillation detector”.
However after purchasing the app and before using it you see this disclaimer which states it is not to be used for any medical diagnosis.
I will be performing a more detailed analysis of this app’s performance in the future and contacting the FDA about the danger such inaccurate medical testing confers on victims.
In the meantime if you have any experience with this app or other apps claiming to detect AF reliably using detection of the pulse from finger application to the camera lens please share them with me (via email DRP@theskepticalcardiologist.com or via comments below.)