24. “I have A-Fib, and my heart doctor wants me to take Xarelto 15 mg. I am concerned about the side effects which can involve death. What else can I do?”
You are right to be concerned about the side effects of Xarelto, one of the new Novel Oral Anticoagulants (NOACs).
All anticoagulants are inherently dangerous. You bruise easily, cuts take a long time to stop bleeding, you can’t participate in any contact sports; there is an increased risk of developing a hemorrhagic stroke and gastrointestinal bleeding. (Most EPs are well aware of the risks of life-long anticoagulation.)
Primary risk: Uncontrolled bleeding is the primary risk (patients have bled to death in the ER.) Anticoagulants cause or increase bleeding. That’s how they work. To decrease your risk of blood clots and stroke, they hinder the clotting ability of your blood. But, they also increase your risk of bleeding.
Normally, clotting is a good thing like when you have a scrape or cut.
Other risks: Do the NOACs have the same long-term problems as warfarin (Coumadin), i.e., microbleeds in the brain, hemorrhagic stroke, early dementia, etc.?
We don’t know yet. The NOACs haven’t been around long enough to determine their side effects. But intuitively one would expect so. (The recent spate of ads from lawyers seeking clients who have been harmed by NOACs would seem to lead to this conclusion.)
Anticoagulants Protect You and Give Peace of Mind
But in spite of the possible negative effects of anticoagulants, if you have A-Fib and a real risk of stroke, anticoagulants do work. You’re no longer 4–5 times more likely to have an A-Fib (ischemic) stroke. Taking an anticoagulant to prevent an A-Fib stroke also may give you peace of mind.
What Else Can You Do? Remove the Reason for an Anticoagulant—Three Options
Be advised: No anticoagulant will absolutely guarantee you will never have a stroke.
The best way to deal with the increased risk of stroke and side effects of anticoagulants is to no longer need them. Here are three options:
#1 Alternative: Get rid of your A-Fib.
As EP and prolific blogger Dr. John Mandrola wrote: “…if there is no A-Fib, there is no benefit from anticoagulation.”
Action: Request a catheter ablation procedure. Today, you can have an ablation immediately (called ‘first-line therapy’). You don’t have to waste a year on failed drug therapies. See Catheter Ablation Reduces Stroke Risk Even for Higher Risk Patients
#2 Alternative: Close off your Left Atrial Appendage (LAA).
The Left Atrial Appendage is where 90%-95% of A-Fib clots originate.
Action: Request a Watchman device. The Watchman device is inserted to close off your LAA and keep clots from entering your blood stream. See Watchman Better Than Lifetime on Warfarin
#3 Alternative: Consider non-prescription blood thinners
Ask your doctor about your CHA2DS2-VASc score (a stroke risk assessor). If your score is a 1 or 2 (out of 10), ask if you could take a non-prescription approach to a blood thinner.
Perhaps you can benefit from an increase in natural blood thinners such as turmeric, ginger and vitamin E or, especially, the supplement Nattokinase. See FAQ: “Are natural blood thinners as good as prescription blood thinners?”
Whether or not to take anticoagulants (and which one) is one of the most difficult decisions you and your doctor must make. Talk to your doctor about alternatives to anticoagulants: Taking an anticoagulant isn’t like taking a daily vitamin. Only take one if you are at a real risk of stroke.
Taking an anticoagulant isn’t like taking a daily vitamin. Only take one if you are at a real risk of stroke.
• Catheter ablation
• LAA closure (Watchman device)
• Non-prescription blood thinners
If you decide to stay on a NOAC, ask your doctor about taking Eliquis instead of Xarelto. Eliquis tested better than the other NOACs and is considered safer. See Warfarin vs. Pradaxa and the Other New Anticoagulants and the FAQ: Is Eliquis Safer.
Thanks to Jim Lewis for this question.
You must be your own best patient advocate.
Don’t settle for a lifetime on anticoagulants or blood thinners.
Last updated: Thursday, May 19, 2016 Return to FAQ Drug Therapies
Warfarin has one, but the NOACs don’t. What am I talking about?
Warfarin (Coumadin) has a way to monitor and measure its effectiveness for a specific patient. But there’s no similar way to measure the effectiveness of the new Novel Anticoagulant drugs (NOACs).
Warfarin and Your INR
With warfarin, blood testing for your INR (International Normalized Ratio) will tell your doctor what dosage of warfarin is needed to maintain your ideal INR range between 2.0 and 3.0. (Below 2.0, there’s more of a risk of an ischemic [clotting] stroke; above 4.0, there’s more of a risk of a hemorrhagic [bleeding] stroke.)
NOACs: No Blood Testing but at What Price?
From the clinical trials we know NOACs work as well as warfarin. In addition, the NOACs don’t require periodic blood testing. But the FDA, under pressure for new anticoagulants, approved the NOACs without there being any established or universally recognized method of determining their clot preventing effectiveness.
Without any method of determining their clot preventing effectiveness, how can you determine if your NOAC is working for you? … Continue reading this report…->
I’ve posted a new FAQ in the Complementary & Natural Therapies section:
“Have there been any tests comparing natural blood thinners to the new anticoagulants (NOACs) in terms of efficacy and speed of onset?”
Comparison testing is unlikely. It’s highly unlikely that pharmaceutical companies and the FDA will one day pay for unbiased tests comparing their products to natural blood thinners. They have everything to lose and nothing to gain. Clinical trials are expensive, so it’s unlikely any others (i.e., the nutritional supplements industry) will have a financial incentive to pursue it either.
Stop Taking Warfarin―Produces Arterial Calcification
The blood thinner, warfarin (Coumadin) is a “vitamin K-antagonist” which works by blocking vitamin K (i.e., K-2, menaquinone), thereby affecting several steps in the anticoagulation pathway and decreasing clotting proteins in the blood.
But vitamin K is also essential for heart and bone health. Vitamin K determines whether we maintain strong bone density and soft pliable tissues. Without enough K-2, osteocalcin, a protein that binds calcium to bone, doesn’t function. This vascular calcification produces plaque and reduces aortic and artery elasticity.
“When calcium doesn’t stay in bones, it can end up clogging your arteries, causing a heart attack or stroke.”
Warfarin Blocks Vitamin K: Deposits Calcium in Arteries
By blocking vitamin K (K-2), warfarin deposits calcium in our arteries and progressively turns them into stone. In the absence of vitamin K, bony structures form in soft tissues. When you hear the term “hardening of the arteries,” this means that previously flexible blood vessels are turning into rigid (calcified) bony structures.
In a study of 451 women using mammograms to measure arterial calcification, after just one month of warfarin use, arterial calcification increased by 50% compared to untreated women. After five years, arterial calcification increased almost 3-fold.
Why You Should You Stop Taking Warfarin
If you are taking warfarin (Coumadin), you should talk to your doctor about switching to Eliquis (apixaban) which tested the best of the NOACs and is the safest. (See my article, Warfarin and New Anticoagulants.)
The new oral anticoagulants (NOACs) do not block vitamin K. But the NOACs do have drawbacks. In the case of severe bleeding, there is currently no antidote or reversal agent like there is for warfarin (a reversal agent for the direct factor Xa inhibitors Xarelto and Eliquis is close to FDA approval).
Added 2015: The FDA approved a reversal agent Praxbind for the NOAC Pradaxa Oct. 16, 2015. In clinical trials, 5gs of Praxbind (idarucizumab) administered by IV reversed the anticoagulant effect of Pradaxa within minutes (which is significantly faster than the current antidotes for warfarin).
Whether or not to be on an anticoagulant and which one to take is the most difficult decision you and your doctor have to make (and your initial decision may change over time as your body changes.)
If you aren’t happy with your doctor’s response, get a second opinion. You need to feel confident and at peace with this decision.
AF Symposium 2015
The Novel Oral Anticoagulants: Xarelto Best Seller
by Steve S. Ryan, PhD, Updated August 2015
Dr. Daniel Singer of Mass General updated our info about the NOACs (Novel Oral Anticoagulants). Rivoraxaban (Xarelto) is now the most commonly prescribed NOAC. (This is somewhat surprising since dabigatran [Pradaxa] was the first NOAC approved by the FDA and for many months was the only alternative to warfarin. But Pradaxa has lost market share, possibly because of the bad publicity about deaths in the ER from not being able to stop bleeding and its law suit settlements.) (See also: Stop Prescribing or Taking Pradaxa: Suspect in 542 Patient Deaths and Warfarin vs. Pradaxa and the Other New Anticoagulants )
NOACs More Prescribed for New Patients Than Warfarin
After a slow start, NOACs are now prescribed by doctors more commonly than warfarin for new A-Fib patients.
How Do We Know Patients are Actually Taking NOACs and Getting Adequate Levels of Anticoagulation?
The obvious problems with NOACs are they are very costly compared to warfarin, and there currently aren’t any reversal agents like there are for warfarin. But Dr. Singer raised another problem. How can we know the patient is taking the NOAC, what anticoagulant level are they reaching? With warfarin we have INR levels and years of experience in monitoring. Dr. Singer thinks that with more time and clinical experience, we may get a better handle on how the NOACs are actually performing.
GI Bleeding Preferable to Brain Bleeds
Some NOACs produce gastrointestinal bleeding and damage. But Dr. Singer pointed out that from his perspective that is acceptable. No one wants to have gastrointestinal bleeding. But compared to intracranial bleeds, GI bleeds are seldom lethal and don’t leave people disabled.
Dr. Singer didn’t venture to distinguish between the various NOACs because there haven’t been any head-to-head trials. But, in this editor’s opinion, Eliquis tested better and is safer than the others.
NOTE: Another NOAC Edoxaban (Lixiana) was approved by the FDA in January, 2015.
Update August 15, 2015:
See also: Edoxaban Compared to Other Blood Thinners.
An experimental drug idarucizumad has show positive results as a reversal agent for Pradaxa (dabigatran). In a new study of 90 patients who had uncontrolled bleeding with Pradaxa, idarucizumad stopped this bleeding within minutes. No serious side effects were reported. FDA approval is pending.
We have previously reported on the reversal agent Andexanet Alfa which is on FDA fast track approval as an antidote to the Factor Xa inhibitors Xarelto and Eliquis. FDA approval is pending.
AF Symposium 2015
All Anticoagulants Cause Bleeding
Updated August 2015
Dr. Peter Kowey of Lankenau Hospital in Wynnewood, PA discussed the special needs of patients with both A-Fib and Coronary Artery Disease (CAD). Sometimes, for example, these patients have to take both anticoagulant therapy for A-Fib and antiplatelets for stents. Some patients wind up taking a combination of three different drugs like warfarin, clopidogrel and aspirin.
Dr. Kowey pointed out how taking combinations of anticoagulants and antiplatelets multiplies the risk of bleeding. He cited the WOEST study which, though small, indicated that there was no real need for aspirin in addition to warfarin and clopidogrel.
All Anticoagulants Cause Bleeding
His most important point Dr. Kowey made for A-Fib patients is that all anticoagulants cause bleeding. That’s how they work. What an EP and an A-Fib patient strive for together is to find the right dose that gives the best protection versus minimizing the chances of bleeding. It’s tricky, because there are so many differences among patients. And it changes over time as we do.
NOACs May Be Dose Dependent
Dr. Kowey also discussed how the new anticoagulants (NOACs) were FDA approved on the assumption that one-size-fits-all, that one dosage works for all patients. But we know that warfarin is dose dependent. One would expect intuitively that the NOACs would work in a similar manner.
Dr. Kowey discussed the recent FDA hearings on the new anticoagulant edoxaban (Savaysa), namely that patients who had very good renal function seemed to get less of an anticoagulant effect. Patients taking the previously FDA approved NOACs may have been underdosed, because most of these drugs are renally eliminated. Unlike the INR measure in warfarin, the NOACs don’t have any standard, recognized way of measuring the anticoagulant effect as a guide to dosing. The one-size-fits-all NOAC dosage may work for most people, but others may be over- or under-anticoagulated.
Though not part of Dr. Kowey’s presentation, recent reports on Pradaxa (dabigatran) indicate that Boehringer-Inglehoff may have known that Pradaxa was dose dependent but didn’t tell the FDA. (See Claim “Misguided” That Pradaxa Needs No Blood-Level Monitoring.)
Taking anticoagulants is a trade-off. For most people, lowering the risk of an A-Fib stroke is a most welcome benefit compared to an added tendency to bleed.
All Anticoagulants Cause Bleeding and Are Dangerous
Anticoagulants are not like taking vitamins. No one wants to take an anticoagulant. Dr. Kowey’s statement that “all anticoagulants cause bleeding” and are inherently dangerous should determine how we look at all anticoagulants. This is in stark contrast with how NOACs are presented in today’s TV advertisements. (Just take an anticoagulant and live happily ever after!)
We obviously don’t have any data on the long-term effects of taking NOACS for years. Some people on long-term warfarin have been known to develop micro bleeds and dementia. Will this happen with the NOACs? We simply don’t know. But intuitively one would expect the same thing to happen, though probably not to the extent of warfarin.
NOACs Dose Dependent?
Dr. Kowey’s presentation also highlighted another important point for A-Fib patients—NOACs are probably dose dependent to some extent. One size does not fit all. If you are taking a NOAC, you may be under- or over-dosed.
How serious a problem is this? We simply don’t know. With Pradaxa many people have died in the ER from bleeding that doctors couldn’t stop. Was this because of over-dosing? It’s hard to tell. (See Stop Prescribing or Taking Pradaxa.)
One wonders how the FDA could have approved new anticoagulants with no standard, proven method of determining the anticoagulants’ effectiveness? (The NOACs were also approved with no reversal agent or antidote in case of bleeding!) But to be fair to the FDA, there was a great need for new anticoagulants to alleviate the problems with warfarin. And from the clinical trials, few could have anticipated the real world NOAC problems.
Update August 15, 2015: Reversal Agent for Pradaxa (dabigatran)
An experimental drug, idarucizumad, has show positive results as a reversal agent for Pradaxa (dabigatran). In a new study of 90 patients who had uncontrolled bleeding with Pradaxa, idarucizumad stopped this bleeding within minutes. No serious side effects were reported. FDA approval is pending.
We have previously reported on the reversal agent Andexanet Alfa which is on FDA fast track approval as an antidote to the Factor Xa inhibitors Xarelto and Eliquis. FDA approval is pending.
Update October 26, 2015: FDA Approves Reversal Agent Praxbind® for the Anticoagulant Pradaxa
Last updated: Wednesday, January 27, 2016
When I think about the field of atrial fibrillation in 2013, several thoughts come to mind. There were technical advancements, some new drug therapies, and additions to our understanding of Atrial Fibrillation (and a few accomplishments for our A-Fib.com website).
Heart Imaging And Mapping Systems
Perhaps the most important technical innovations in 2013 for A-Fib patients were the introduction of two new heart imaging and mapping systems. A third system, the Bioelectronic Catheter, represents a whole new technology with tremendous potential for A-Fib patients.
The ECGI System
The ECGI system, combined with a CT scan, produces a complete 3-D image of your heart along with identifying all the A-Fib-producing spots. Think of it as an ECG with 256 special high resolution electrodes rather than 12. It greatly reduces your ablation time and your radiation exposure.
A day before your ablation, you simply don a special vest with 256 electrodes covering your upper torso, and lay down. The 3-D image created is a road map of your heart with all the focal and rotor areas (A-Fib-producing spots) identified. During your ablation your EP simply ablates the “guilty” areas. Read more of my article…
The FIRM System
The FIRM system uses a different approach to mapping the heart and the A-Fib producing spots. It uses a basket catheter inside the heart to map large areas in a single pass and reveal the location of foci and rotors. Read more of my article…
Why are these two technologies important? ECGI allows your imaging & mapping to be performed the day prior to your ablation, rather than during your ablation. This shortens the length of your ablation procedure. In addition it reduces your radiation exposure and produces remarkably accurate 3D images of your heart and identifies where A-Fib signals are coming from. The FIRM system, though performed during an ablation rather than before it, may be a significant improvement over the Lasso catheter mapping system now in current use. Both systems may mark a new level of imaging/mapping for A-Fib.
Stretchable Electronics Meets the Balloon Catheter
The merging of living systems with electronic systems is called “bioelectronics”. Key is a flexible, pliable circuit made from organic materials—the carbon-based building blocks of life. Bioelectronics have entered the EP lab with a prototype of a ‘bioelectronic catheter’, the marriage of a pliable integrated circuit with a catheter balloon.
In a mapping application, the deflated bioelectronic balloon catheter is slipped into the heart, then pumped up. The inflated integrated circuit conforms to the heart’s grooves and makes contact with hard-to-reach tissue. It can map a hundred electrical signals simultaneously, across a wider area and in far greater detail than had been previously possible. And it’s being developed to function in reverse. For ablation applications, instead of detecting current, it can apply precise electrical burns. This is a potentially breakthrough technology that may well change the way catheter mapping and ablation are performed. (Thanks to David Holzman for calling our attention to this ground-breaking research article.)
This is a remarkable time in the history of A-Fib treatment. Three very different technologies are poised to radically improve the way A-Fib is detected, mapped and ablated. We’ll look back at 2013 as a watershed year for A-Fib patients.
Three New Anticoagulants
In 2013 we saw three new anticoagulants, a welcome development for A-Fib patients. Note: the new anticoagulants are very expensive compared to the proven anticoagulant warfarin.
How do they compare to warfarin?
Warfarin seems to have a slightly higher chance of producing intracranial bleeding.
In general stay away from Pradaxa. There are horrible ER reports of patients bleeding to death from even minor cuts, because there is no antidote or reversal agent. Read more about my Pradaxa warning…
Eliquis, in general, tested better than Xarelto in the clinical trials, but it’s so new we don’t have a lot of real-world data on it yet. And, as with Pradaxa, neither have antidotes or reversal agents.
In addition, there was what some consider a major problem with the clinical trials comparing the new anticoagulants to warfarin. ‘Compliance’ rates by warfarin users were poor (many either weren’t taking their warfarin or weren’t in the proper INR range). Did this skew the results?
And finally, unlike warfarin where effectiveness can be measured with INR levels, we don’t have any way to measure how effectively the new blood thinners actually anticoagulate blood. Read more of my article “Warfarin vs. Pradaxa and the Other New Anticoagulants“.
Keep in mind: ‘New’ doesn’t necessarily mean ‘better’ or ‘more effective’ for You.
High Blood Pressure with Your A-Fib? Is Renal Denervation a solution?
As many as 30% of people with A-Fib also have high blood pressure which can’t be lowered by meds, exercise, diet, etc. There was hope that Renal Denervation would help.
With Renal Denervation, an ablation catheter is threaded into the left and right arteries leading to the kidneys, then RF energy is applied to the nerves in the vascular walls of the arteries, hopefully reducing ‘Sympathetic Tone’, lowering high blood pressure and reducing A-Fib. For many people Renal Denervation seemed the only realistic hope of lowering their high blood pressure. However, the Medtronic Simplicity-3 trial indicated that renal denervation doesn’t work. Read more of this article… For 2014 news on this topic, read more…
A Study of Obesity and A-Fib: A-Fib Potentially Reversible
Obesity is a well known cause or trigger of A-Fib, probably because it puts extra pressure and stress on the Pulmonary Vein openings where most A-Fib starts.
In 2013 A research study report focused on obese patients with A-Fib. Those who lost a significant amount of weight also had 2.5 times less A-Fib episodes and reduced their left atrial area and intra-ventricular septal thickness.
Good news! Losing weight can potentially reverse some of the remodeling effects of A-Fib. Related article: Obesity in Young Women Doubles Chances of Developing A-Fib.
Obstructive Sleep Apnea and A-Fib
Obstructive Sleep Apnea (OSA) is another well recognized cause or trigger of A-Fib. Anyone with A-Fib should be tested for sleep apnea.
Earlier studies have shown approximately two-thirds (62%) of patients with paroxysmal or persistent A-Fib suffer from sleep apnea. In 2013, research reports showed that the worse one’s sleep apnea is, the worse A-Fib can become. In addition, sleep apnea often predicts A-Fib recurrence after catheter ablation.
Before an ablation, Dr. Sidney Peykar of the Cardiac Arrhythmia Institute in Florida, requires all his A-Fib patients be tested for sleep apnea. If they have sleep apnea, they must use CPAP therapy after their ablation procedure.
A-Fib.com: Our New Website’s First Year
The original A-Fib.com web site was created using the phased out software MS FrontPage. Thanks to a “no strings attached” grant from Medtronic, A-Fib.com was reinvented with a more up-to-date but familiar look, and features more functionality (built on an infra-structure using Joomla and WordPress). We can now grow the site and add features and functions as needed.
It involved a tremendous amount of work. A special thanks to Sharion Cox for building the new site and for technical support. My wife, Patti Ryan, designed the look and all graphics. (I can’t thank Patti enough; I’m so lucky!)
Update the Directory of Doctors & Facilities
Back when I started A-Fib.com in 2002, there were less than a dozen sites performing ablations for A-Fib. Today our Directory of Doctors and Facilities lists well over 1,000 centers in the US, plus many sites worldwide.
Increasingly, doctors were writing me asking why they weren’t included, or why their info was incorrect since they had moved, etc. To update our records and our service to A-Fib patients, starting in July 2013, we prepared and mailed letters to over 1,000 doctors/facilities. We asked each to update/verify their listing (and include a contact person for our use).
The response to our bulk mailing was great. The data input started in October and continued for several months (as time allowed). Recently, we cut over to the ‘new’ Directory menu and pages.
What’s Ahead for A-Fib.com in 2014
2014 Boston AFib Symposium Reports: Check out my new reports from the 2014 Boston A-Fib Symposium (BAFS) held January 9-11, 2014 in Orlando FL.
The first two reports are posted. Look for more reports soon. I usually end up with 12-15 reports in total.
Our a-Fib.com Directory of Doctors & Facilities: Work on updating our listings is still underway. We need to contact those who did not respond to our request for verification or updating of their listing. (Shall we write again or maybe make phone calls?)
Amazon Best Sellers list: Our book sales continue to grow. Did you know that our book ‘Beat Your A-Fib’ has been on Amazon’s Best Sellers list continually in two categories (Disorders & Diseases Reference and Heart Disease) since its debut in March 2012? Visit Amazon.com and read over 40 customer reviews.
Help A-Fib.com Become Self-sustaining: We plan to step up our efforts to make A-Fib.com a self-sustaining site. (Since 2002, Steve and Patti Ryan have personally funded A-Fib.com with an occassional reader’s donation.)
In our efforts toward sustainabiliy, several years ago we added a PayPal ‘Donate’ button (you don’t need a PayPal account to donate) and invited donations toward our onlline maintenance costs.
Our newest effort is our ‘A-Fib can be Cured! shop with T-shirts and more at Spreadshirt.com. With each shirt purchase $2 goes to support A-Fib.com. (We will roll out new designs every quarter or so).
Posted February 2014
Help A-Fib.com become self-sustaining! Help keep A-Fib.com independent and ad-free.
Will 2014 be the year you help support A-Fib.com?
Last updated: Wednesday, February 11, 2015
20th Annual AF Symposium
by Steve S. Ryan, PhD
This overview should give you a sense of the topics floating through the three days in Orlando and the over sixty presentations by fifty A-Fib experts and researchers. (Most recent brief reports listed first)
(Please be advised that the Symposium organizers go to great lengths not to identify or unfairly publicize one device over another. When writing these reports I often have to do a good deal of research to correctly identify and describe particular devices that are demonstrated, as a service to readers. But this in no way implies or suggests that one device is superior to another.)
Dr. Gerhard Hindricks of the University of Leipzig in Germany gave a dynamic presentation of a catheter ablation of a 46-year-old female with paroxysmal A-Fib using the Rhythmia 3-dimensional multipolar mapping system by Boston Scientific. Along with his colleagues Drs. Andreas Bollmann and Jedrzej Kosiuk, they used the Rhythmia special basket catheter to generate a 3-D map of electrogram voltages and activation times. To me it seemed amazingly fast. The eight-splined bidirectional catheter produced 1,000 data points per minute. In what seemed like only a few passes, they produced a 3-D color reconstruction of the patient’s left atrium.
The actual ablation was routine. They terminated the A-Fib into sinus rhythm without having to use Electrocardioversion. But they found that the PV isolation was incomplete. Using the same Rhythmia 3-D mapping catheter, they were easily and quickly able to locate the gap in the Left Superior PV and ablate it.
Dr. Vivek Reddy from Mount Sinai School of Medicine in New York City gave a very well referenced and persuasive presentation on the Watchman device which closes off the Left Atrial Appendage to prevent clots and strokes. The theory behind the Watchman device is that most A-Fib clots originate in the Left Atrial Appendage (LAA). The Watchman closes off the LAA where 90-95% of A-Fib strokes come from. It’s a very low risk procedure that takes as little as 20 minutes to install. Afterward, you would usually not need to be on blood thinners. (For more, see my article, The Watchman Device: The Alternative to Blood Thinners).
Dr. Reddy certainly persuaded me that the FDA should approve the Watchman device. Dr. Reddy, earlier in Washington, had made the same persuasive arguments before the FDA.
Dr. Andrew Farb from the FDA took the bull by the horns and gave his perspective on the various LAA Closure (Occlusion) Devices. But as one would expect, he didn’t indicate how the FDA would rule on the Watchman device, since deliberations were still ongoing.
After his presentation, I asked him several pointed questions about this, but he was, of course, careful not to comment about current FDA deliberations. My guess? If body language, momentum, mood of the presentations, and more importantly recent research indicate anything, the Watchman device probably will not be approved by the FDA.
There was a palpable sense of sadness at the end of these presentations. The attendees realized that the game may be over for the Watchman device. I hope I am wrong, since the Watchman device would be an important tool to help A-Fib patients. Once the FDA rules and the current clinical trials of the Watchman device end, you will probably have to go to Canada or overseas to get a Watchman device installed.
(Happily I was wrong on this prediction. Update: The U.S. Food and Drug Administration (FDA) approved Boston Scientific’s WATCHMAN™ LAA closure technology for use in the U.S. on March 13, 2015. It has been available internationally since 2009. The FDA approval of the WATCHMAN device is based on the clinical program which consists of numerous studies, with more than 2,400 patients and nearly 6,000 patient-years of follow-up. The Watchman device will be available first at U.S. centers where it has been used in clinical studies.)
Watchman May Win FDA Approval
In my earlier brief reports on the Orlando AF Symposium, based on the recent research and the FDA presentation, I said the Watchman device probably won’t be approved in the US. I’m happy to say that I am most likely wrong.
At the LAA Symposium 2015 in Marina del Rey, CA, it was suggested that the Watchman device may be approved by the middle of this year. One presenter described how the FDA chairman talked with several people who were going to Canada to have the Watchman device installed. He seemed embarrassed that the Watchman was available everywhere in the world but not in the US and said that it has to be approved.
Other doctors I talked with at the LAA Symposium were of the same opinion. Presenters described how clinical trials for other LAA closure devices were on hold so that they could get approved in comparison to the Watchman (Non-Inferiority Trials). Dr. Dhanunjaya Lakkireddy of the University of Kansas Medical Center said that we are at a “tipping point” for the (A-Fib) industry.
As everyone, including the FDA, is well aware, A-Fib innovations usually start in Europe where they are more easily approved. Then only later do they move to the US for FDA approval, since the FDA generally requires more data than European regulators.
Drs. Jun Dong and Andrew Farb from the FDA described the FDA’s ‘Easy Feasibility Study’ (EFS) program where medical device innovations could be evaluated in the US without having to go to Europe first. He encouraged researchers and attendees to take advantage of the new EFS program. This is major news and may make the development of A-Fib innovations much easier to accomplish in the US.
For further information, contact: Andrew Farb, Email: Andrew.firstname.lastname@example.org. 301-796-6317
Dr. Luigi Di Biase from the Albert Einstein College of Medicine in the Bronx, NY and Dr. Daniel Singer from Massachusetts General Hospital in Boston each described potentially great developments in reversal agents for apixaban (Eliquis) and rivaroxaban (Xarelto).
Dr. Di Biase described studies where leaving people on uninterrupted rivaroxaban and apixaban before, during and after an ablation dramatically reduced the amount of silent thromboembolic lesions and were as safe as warfarin with regards to stroke and TIAs. (This didn’t work with dabigatran [Pradaxa].) But if patients develop bleeding or effusion during the ablation, they are in trouble because there is no direct reversal agent as there is for warfarin. He has used Factor IV as an indirect reversal agent. Dr. Singer also described how Factor IV was used as a reversal agent for apixaban.
But there are new reversal agents for apixaban and rivaroxaban which promise to completely reverse the effects of these two drugs in less than four minutes. The FDA is speeding up studies on these reversal agents. But one never knows when or if the FDA will approve them.
Dr. John Day of the Intermountain Heart Institute in Murray, UT (and recently elected president of the Heart Rhythm Society) may be the first A-Fib leader to publicly question whether women should be given one point on the stroke risk CHA2DS2-VASc scale just because of their gender. Many doctors have said this in a circumspect way. Dr. Eric Prystowsky in a presentation at last year’s AHS meeting thought that most doctors would agree with Dr. Day, “as long as there wasn’t a camera focused on them.” He gave the example of a 45-year-old woman in good health and a 45-year-old man with hypertension who according to current guidelines should both be given one point on the stroke risk CHA2DS2-VASc score.
As readers of A-Fib.com, you know that’s been my opinion ever since the original European guidelines came out. Women in their child-bearing years are much less at risk of stroke because of the blood-thinning effect of losing blood each month. And even after menopause women have less risk of stroke. But eventually they do have more strokes. But not because of an innate inferiority, but because women live longer than men. Stroke is age related. An observational Danish registry study documents this.
For more, see The Denmark Study: Women in A-Fib Not at Greater Risk of Stroke Contrary to CHA2DS2-VASc Guidelines!) (Be advised that the original European guidelines were written by doctors with major conflicts of interest.) These guidelines may be a not so very subtle form of gender bias.
Living in A-Fib is more dangerous than having an ablation, according to Dr. Josef Kautzner from Prague, the Czech Republic. Studies have documented that the adverse effects of living in A-Fib, having to take A-Fib drugs and anticoagulants for life are both pragmatically and statistically worse than having an ablation. Dr. Kautzner discussed how A-Fib can cause or is associated with silent brain lesions and dementia. Any time you go into a hospital is a risk. And no one would say that a catheter ablation is a walk in the park. But an ablation is a low risk procedure, though not risk free. The risk is similar to having your tubes tied. The possible adverse effects of an ablation procedure (like bleeding at the groin) are generally temporary, unlike the lasting, permanent damage you can do to your heart, body and brain by living in A-Fib for years.
The most hotly discussed topic at this year’s symposium was rotors. The opinions expressed about rotors were at times very heated, more than I had ever seen at an AF Symposium. Dr. Shih-Ann Chen of Taipei, Taiwan disagreed with Dr. Sanjiv Narayan of Stanford, CA about the basic concepts of rotors and how they should be defined. Dr. Ravi Mandapati of UCLA and Loma Linda University disagreed with Dr. Narayan which was all the more striking in that he had worked with Dr. Narayan when he was at UCLA. Dr. Pierre Jais of Bordeaux, France said that the FIRM mapping system misses 40% of the atrium area.
Drs. Haissaguerre and Jais from Bordeaux and Dr. Sebastien Knecht of Brussels, Belgium gave presentations on how they were using the CardioInsight body surface mapping vest to perform ablations of “drivers” at many different centers, while Dr. Karl-Heinz Kuck from Hamburg, Germany using a different body surface mapping system said that he couldn’t ablate rotors. Dr. Narayan says the FIRM system finds a maximum of 2-3 rotors in the atria, while other systems find as many as seven. The FIRM system says rotors are usually relatively stable and can last as long as 30 seconds while others say they rotate in one fixed spot for only one or two rotations, that they tend to migrate within a certain area.
The presenters obviously didn’t share a consensus of basic concepts of what rotors are, how they work, their importance in A-Fib, how they should be correctly identified, used, and ablated. (It seems to me the Bordeaux group has the best understanding and pragmatic use of rotors. They refer to “rotors” and focal sources as “drivers.”) But the CardioInsight system Bordeaux uses isn’t currently available or isn’t being tested in the US.
Obesity was one of the most often discussed topics. There is a growing consensus among EPs that it isn’t enough to just give obese patients a catheter ablation while not dealing with their obesity. If the obesity isn’t dealt with, their A-Fib is very likely to re-occur. A-Fib will develop in other spots that haven’t been ablated. The condition (obesity) that triggered or caused the A-Fib will trigger or cause it again, if it isn’t taken care of.
Dr. Prashanthan Sanders of Adelaide, Australia described the great results he is getting in his clinic which includes a weight loss program and counseling. He convinces his overweight patients to buy into the program, lose weight, and keep it off. The program works so well that just by losing weight patients become A-Fib free. This program is a holistic approach to health and also is developed to work for diabetes, sleep apnea, hypertension, binge drinking and smoking.
Dr. Sanders foresees a world where some patients become A-Fib free simply by changing their life style, where they don’t have to have a catheter ablation to become A-Fib free.
Many other doctors commented that A-Fib treatment at many centers today includes or should include much more than A-Fib ablation and drugs. A-Fib centers should have nutritionists, exercise therapists, sleep apnea specialists, etc. as part of their A-Fib program.
Dr. John Day of the Intermountain Heart Institute in the Challenging Cases Discussion described his experience with the dreaded Atrial Esophageal Fistula. Though very rare, this is one of the few possible complications of a catheter ablation that can kill you. An ablation, if not done with caution, can irritate and damage the esophagus which often lies right next to the heart. Over 2-3 weeks stomach acid can eat through this damaged area to produce a hole or fistula from the esophagus into the heart.
As soon as Dr. Day saw this patient, he knew it was a fistula and immediately called surgeons and a GI doctor. All the surgeons were doing operations and didn’t want to do the surgery in the EP lab. Dr. Day described how he and his colleagues ran down the hospital hallway to the operating room while giving the patient a transfusion and at the same time pumping out the blood escaping from his heart.
The GI doctor got there first and put in a stent in the esophagus to plug the hole. There was lots of discussion as to whether this was the best approach, but it worked. The patient survived but had to spend a month in the hospital.
This cautionary and very dramatic tale certainly got the attention of all the attendees. No matter how rare a fistula is, every EP and A-Fib center must have an established protocol in place to deal with it. I remember Dr. Hugh Calkins in a previous Symposium advising, “There are only two kinds of EPs—those who have not had an Atrial Esophageal Fistula and those who have!” (Dr. Calkins’ patient with fistula also survived.)
Dr. Peter Kowey of Lankenau Hospital in Winnewood, PA described a case that illustrates the kind of dilemma both doctors and patients often have to face. A 92-year-old woman with paroxysmal A-Fib who had been treated for many years with warfarin had some bruising and nuisance bleeding, but never anything major.
Dr. Kowey thought that ethically he should tell her about the different new anticoagulants which may be superior to warfarin, then see if she wanted to change. She went with apixaban (Eliquis), then six months later had a stroke even though she was taking apixaban properly and conscientiously. Happily, she made an almost full recovery. She returned to warfarin which had worked for her in the past and which she was comfortable using.
One of the reasons Dr. Kowey discussed the new anticoagulants with his 92-year-old patient was because warfarin is considered more apt to cause bleeding in older patients. The newer anticoagulants in clinical trials caused less bleeding. But we don’t have much data from the clinical trials on people over 90 years old.
Can we say that apixaban didn’t work or was ineffective? No. Anticoagulants reduce but do not totally eliminate the risk of an A-Fib stroke. Just because she had a stroke doesn’t mean apixaban didn’t work.
Dr. Jeremy Ruskin pointed out that there has never been and probably never will be a head-to-head comparison of the three new anticoagulants. But in my opinion apixaban (Eliquis) appears to have tested better and is safer than the others
For more, see my 2013 BAFS articles, The New Anticoagulants (NOACs) and Warfarin vs. Pradaxa and the Other New Anticoagulants.
In the satellite case live presentations, Drs. Rodney Horton and Amin Al-Ahmad from the Texas Cardiac Arrhythmia Institute in Austin, TX surprised us by doing an ablation without wearing the standard lead aprons to prevent fluoroscopy exposure. Even more surprising was one of the lab assistants who was pregnant. She could work on the ablation because no fluoroscopy was used. The doctors did the whole ablation using ICE (Intracardiac Echo) and 3D mapping. They showed for example how ICE can be used to thread the catheter up into the heart and into the left atrium. Dr. Horton said that not having to wear those heavy lead aprons would probably add 5-10 years to his ablation career.
(They didn’t wear surgical masks during the ablation which was surprising to me. I will write them for an explanation.)
The live satellite case from Beijing, China was technically flawless and probably a first of its kind. But it wasn’t much of a learning experience for the attendees. The Chinese EPs only used one catheter and had to frequently pull out the mapping catheter and replace it with the ablation catheter, etc. When the expert panel asked them questions, the Chinese EPs either didn’t understand or simply didn’t answer them. They seemed very uncomfortable. It seemed like a throwback to ablation techniques of 20 years ago.
Drs. Claudio Tondo, Gaetano Fassini, Massimo Moltrasio, and Antonio Dello Russo from Milan, Italy showed how they do a catheter ablation for A-Fib and install the Watchman device in the same procedure, when it’s needed. They do the ablation procedure first. Then when the patient is in sinus rhythm, they install the Watchman device. (This can’t be done in the US, because the Watchman device hasn’t received FDA approval. In later discussions including representatives of the FDA, there was an all too real possibility that the Watchman will never receive FDA approval.)
Drs. Kevin Heist and Moussa Mansour from Massachusetts General in Boston showed in a live case how they used a Contact Force Sensing catheter combined with Jet Ventilation. (There are two Contact Force Sensing catheters approved by the FDA—the ThermoCool Smart Touch device by Biosense Webster (approved Feb. 24, 2014) and the TactiCath Quartz Contact Force Ablation Catheter by St. Jude Medical (approved Oct. 27, 2014). This live case used the TactiCath catheter but didn’t imply or suggest it is superior to the ThermoCool catheter. For a description of each, see my 2014 AF Symposium report The New Era of Catheter Ablation Technology: Force Sensing Catheters.
This combination of Force Sensing Catheter with Jet Ventilation for RF ablation probably represents the most advanced RF ablation strategy available today. Jet Ventilation doesn’t stop the heart from beating as in bypass surgery. But to this observer it seemed to put the heart in a type of slow motion with a lot less movement than when the heart is beating in normal sinus rhythm. You could really see a difference when they turned the Jet Ventilation off and on. Slowing down the heart like this helps the ablation doctor make lesions in hard-to-access areas and makes it easier to hold the catheter steady and apply the right contact pressure.
Drs. Michel Haissaguerre and Pierre Jais from Bordeaux/LYRIC gave presentations on the ECGI system. The day before their ablation, the patient lies down on his/her back and a technician places a vest-like device with 256 electrodes over his/her chest and stomach. These electrodes combine with rapid CT (Computed Tomography) scans to produce a very detailed 3D color map of the heart. (For a detailed description and discussion of the ECGI system, see 2013 BAFS: Non-Invasive Electrocardiographic Imaging [ECG]) The system automatically detects rotors and foci and computes them into a “Cumulative Map” or movie. These driver regions are ranked, based on statistical prevalence.
Then, Dr. Sebastien Knecht from CHU Brugmann, Brussels, Belgium, described the AFACART trial design and preliminary results using the CardioInsight ECGI system. Many centers in Europe including four in Germany are now using the CardioInsight. Requiring very little training, technicians and EPs using the CardioInsight system are getting similar great results like the Bordeaux group. Though these studies just started, it looks like the CardioInsight ECGI mapping and ablation system is poised to revolutionize the way EPs map and perform ablations.
Dr. Jose Jalife of the University of Michigan in Ann Arbor, MI, continued his exciting research on fibrosis and A-Fib. In previous Symposiums Dr. Jalife demonstrated how A-Fib produces fibrosis. When he paced sheep into A-Fib, their hearts became fibrotic within a very short time. The markers of fibrosis (collagen and scarring) increased progressively as the sheep went from paroxysmal to persistent A-Fib. (See A-Fib Produces Fibrosis—Experimental and Real-World Data.)
Fibrosis is tissue that has fiber-like characteristics which develop in place of the normal smooth walls of the heart. Fibrotic tissue is scarred, immobile, basically dead tissue with reduced or no blood flow and no transport function. It results in a loss of atrial muscle mass. Over time it makes the heart stiff, less flexible and weak, overworks the heart, reduces pumping efficiency and leads to other heart problems. Fibrosis, up to now, was considered permanent and irreversible. But Dr. Jalife gave his sheep a Gal-3 inhibitor GM-CT-01 that actually prevented and reduced fibrosis! (For his previous presentations, see 2014 BAFS: The Holy Grail: Preventing A-Fib by a GAL-3 Inhibitor.)
In his continuing studies of sheep, Dr. Jalife found that fibrosis predicts recurrence, and that fibrosis can not be reversed if it is well established, even with GAL-3 Inhibitors.
Last updated: Friday, November 18, 2016