Reversal Agent for Eliquis and Xarelto Receives FDA “Fast-track” Approval

 

This is great news for people with atrial fibrillation (AF) who take the newer anticoagulants Eliquis or Xarelto. According to a recent article in Cardiology News the FDA, in early May 2018, approved Andexxa (Portola Pharmaceuticals), the first reversal agent for the popular newer anticoagulants Eliquis and Xarelto.

I think runners and mountain bikers, correctly, worry about problems with excessive bleeding while on anticoagulants because we are certainly at increased risk of falls or of being hit by a car, and many have hesitated to transition from warfarin (Coumadin) because of the lack of a reliable reversal agent.

Pradaxa (dabigatran) and warfarin both already have reversal available reversal agents.

Andexxa acts as a decoy molecule and essentially binds to the drug preventing it from interacting with clotting factors.

Terrific news, right?

According to drugs.com “In the U.S. alone in 2016, there were approximately 117,000 hospital admissions attributable to Factor Xa inhibitor-related bleeding and nearly 2,000 bleeding-related deaths per month.” 

But wait – there’s catch!

Andexxa has been approved but as the writing of this blog post (May 23, 2018) it is not yet available. It exists, but you can’t get it!

I called one of the pharmacists at our hospital (Sky Lakes Medical Center) and asked if it was going to be readily available at our hospital – that’s when I discovered that it wasn’t yet being distributed – but she told me that our hospital plans to have it in stock and available for use.

She also said that once Andexxa is actually available our hospital would then develop guidelines for usage of the new drug. These have not yet been declared but she expects that it will be similar for guidelines pertaining to the reversal agents for Pradaxa and warfarin which are 1.) Patients with serious, life threatening bleeding and 2.) Patients who need emergency surgery.

I think that means that people having elective surgery (like a knee replacement) will not be eligible and will have to taper off their anticoagulant and bridge with Lovenox, just like they do now. I imagine that emergency surgery refers to surgery that is necessary to save your life, not necessarily surgeries like fracture repair, where it would be possible to wait a few days.

As far as my personal experience – I take warfarin and don’t intend to change. I had taken Pradaxa for several years and was very happy with it until I had a mini-stroke and a trans-esophageal echocardiogram revealed that I had a blood clot in my left atrium.

The next big question, of course, is how much will Andexxa cost? I have no idea and I can’t find any information about cost – but I’m guessing it will be really expensive. But then again – people who are anti coagulated and have life threatening bleeding or need emergency life-saving surgery can just go ahead and get Andexxa and worry about how to pay for it later.

 

Any comments are appreciated! Thanks for reading.

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Watchman Device Update

A little one a year ago I wrote about the Watchman device. People with atrial fibrillation often develop a blood clot in the part of the left atrium called the left atrial appendage. This Watchman device basically closes off this area to prevent clot formation.

Last time I wrote the device was relatively new (long term data wasn’t yet available), and based on my research it didn’t seem like a great choice. I would refer you to this excellent article on John Mandrola, MD’s blog: Say No to Watchman.

As a person who has already had a ministroke and a verified blood clot in my left atrial appendage, well yes, I am very interested in a device that would prevent me from having a stroke which, at this point, for me, seems pretty much inevitable. Technology improves over time, right?

So what is going on with the Watchman now?

Well, Boston Scientific released its final five year outcome data from the PREVAIL study, along with five year outcome data from the PROTECT-AF trial. I would refer you to an excellent article in Cardiac Rhythm News (link).

At first look I was fairly optimistic:

In the PREVAIL and PROTECT-AF randomized clinical trials, LAAC with the WATCHMAN device was compared to warfarin for stroke prevention in high-risk patients with non-valvular AF. In addition to stroke prevention comparable to warfarin, the analysis concluded the WATCHMAN device also effectively reduced non-procedure related major bleeding, disabling or fatal stroke, and mortality.

Source Cardiac Rhythm News

I had been thinking the best course of action would be to, perhaps, have a Watchman implant and just remain anti coagulated. After researching this, however, that doesn’t seem like a good plan. The Watchman device has been shown to protect from strokes with an outcome similar to warfarin; but it turns out most of the additional benefit of the Watchman is basically related to the fact that those patients didn’t suffer as many warfarin related side effects/deaths from strokes caused by bleeding or from other major bleeds:

The analysis confirmed a 55% reduction in disabling or fatal stroke, largely driven by an 80% statistically significant reduction in hemorrhagic stroke. Further, the combined data demonstrated a 52% decrease in non-procedure related major bleeding and 27% reduction in all-cause mortality when compared to long-term warfarin therapy

Source Cardiac Rhythm News

At best, regrettably, the Watchman device might be equivalent to warfarin as far as stroke prevention is concerned, but not necessarily better. At best, I think, it would be a good choice for people who have had problems (such as bleeding) with warfarin; but it hasn’t been tested on people who are not eligible for anticoagulation (who are generally less healthy patients). And the Watchman hasn’t been tested against the newer anticoagulants (Pradaxa, Eliquis, Xarelto) which may actually be more effective than warfarin.

So I’m just going to keep watching and hoping for a better option than the Watchman device. I’d be interested in your opinions, and especially in the opinions of anybody reading this who has had a Watchman implant. Please comment below.

Runners with Atrial Fibrillation – Considering the Watchman?

Are you considering the Watchman device?

Watchman_2

Ever since having a TIA/stroke, I certainly have thought a lot about it.

What is it? The Watchman, by Boston Scientific is a little device, sort of like a basket, that can be inserted into the left atrial appendage, theoretically blocking it off and preventing clot formation. As you probably know already, clot formation may lead to Stroke. The device was FDA approved in the US in March, 2015, and has been used in Europe since 2005.

It’s placed in the left atrial appendage via a catheter through an artery in the groin, and if all goes well the patient can discontinue their blood thinner (warfarin, etc.) within six months.

Sounds great, doesn’t it?

I know I’d love to be protected from having another TIA or stroke and not have to take a blood thinner – I’m currently on warfarin + aspirin which makes bicycling, especially mountain biking, quite hazardous. But truthfully, it’s not that I necessarily want to be off the warfarin: I just don’t want to ever have another TIA/stroke. Recall that I had my event while I was already taking Pradaxa (and I never missed a dose). I just want a treatment that is going to work.

trail

But there is some evidence to suggest the Watchman might not be as terrific as it sounds.

A recent study showed that the risk of a major bleed over the course of three years is the same with the Watchman compared to just staying on warfarin. Huh?

This is an excerpt from a Medscape article:

Patients with atrial fibrillation (AF) who received a left atrial appendage closure device (Watchman, Boston Scientific) or stayed on long-term warfarin therapy had similar rates of major bleeding during a mean follow-up of 3.1 years, in pooled analysis of two randomized clinical trials[1]. However, patients who received the device and were able to stop taking warfarin and clopidogrel at 6 months had lower rates of major bleeding from then onward, compared with patients receiving long-term warfarin.

Furthermore, in a very thoughtful, somewhat technical, article CMS Proposal on Watchman Is the Right Decision, Dr John Mandrola, a thought leader in Cardiology and Electrophysiology, agrees with the CMS proposal that “the evidence is sufficient to determine percutaneous left atrial appendage closure therapy using an implanted device is not reasonable and necessary.”

dogwalking

There are two major studies in the US regarding the Watchman. According to Dr Mandrola in the PREVAIL study, “Due to an excess of ischemic strokes, Watchman did not reach noninferiority in this category in the updated analysis presented to the FDA.” In PROTECT-AF study, “ischemic strokes were numerically higher in the Watchman group.” Which, ultimately, “leads one to conclude that the device is not effective.”

As for me, personally, as much as I’d like to believe the Watchman is a solution for me, the evidence, so far, is not convincing. I’m going to wait.

By the way, if any readers have experience with the Watchman PLEASE leave a comment below. We would love to hear from you!

Adverse effects of the Watchman:

“The main adverse events related to this procedure are pericardial effusion, incomplete LAA closure, dislodgement of the device, blood clot formation on the device requiring prolonged oral anticoagulation, and the general risks of catheter-based techniques (such as air embolism). The left atrium anatomy can also preclude use of the device in some patients.”

By the way – I linked a couple of articles from Medscape. I’m not certain but I think you need to be registered for that sight. Sorry.

Warfarin Withdrawal in Patient’s Awaiting Surgery Increases the Risk for Stroke

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Last April Dr. Adnan I. Qureshi reported on research, at the 67th Annual Meeting of the American Academy of Neurology, that has shown that atrial fibrillation patient’s who are taken off of warfarin for surgical procedures have an increased likelihood of having a stroke.

Subjects included in the analysis had atrial fibrillation plus at least one additional risk factor for stroke or death: age >65 years, systemic hypertension, diabetes, congestive heart failure, transient ischemic attack, prior stroke, left atrium diameter 50+ mm, left ventricular fractional shortening <25%, or left ventricular ejection fraction <40%.

Specifically atrial fibrillation patients who discontinued warfarin for surgical procedures had a 1.1% rate of stroke while atrial fibrillation patients who remained on warfarin had a 0.2% rate of stroke.

Read more here:

Warfarin withdrawal in atrial fibrillation patients awaiting surgery dramatically ups stroke risk

Well, this seems like one of those articles where you read the headline and think, “Duh!” Like the article about how obese children have a higher chance of hypertension – No kidding?

Obviously if you are on a medication, in this case warfarin, to prevent having a stroke, and you stop taking the medication, well, you have an increase likelihood of having a stroke. I think everybody suspected this – but what we see here is that the rate of stroke increases five-fold. Wow – that seems incredible!

This article reinforces my strong belief that strict compliance with taking my medications, especially warfarin, is a good idea!

As far as surgery is concerned, clearly, if you need to have the surgery and you need to go off the warfarin, then so be it. The article didn’t mention anything about bridging with Lovenox. You might want to ask your surgeon about that. And also – consider how important the surgery is to your general health. Is the surgery truly necessary? Is it worth risking a stroke?

La Muerte Tocando Guitarra

Runners with Atrial Fibrillation – Thinking About Having a Cardioversion? “Look Before You Shock”

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This is, so far, the most discouraging article about atrial fibrillation I have ever read:

Left Atrial Appendage Thrombus When Least Expected: Look Before You Shock, Evaluate Before You Ablate | EP Lab Digest

As a distance runner with atrial fibrillation, who never missed a single dose of my anti-coagulant, and who has already had a blood clot in my left atrial appendage, and has already had a “mini-stroke” – this one leaves me feeling a bit hopeless.

Feel free to read the article; but I will go over a few key points here. One of the dreaded consequences of atrial fibrillation is having a stroke. Because the top chambers of the heart, the atria (plural of atrium) are beating so fast that they are basically just sitting there vibrating, the blood pools and becomes sluggish, and is prone to forming blood clots. Combine this with an enlarged left atrium and the likelihood is even higher. The blood clot forms in a little corner of the heart called the “left atrial appendage” (LAA).

appendage

That’s where I formed a clot. If the blood clot, or a piece of the clot, breaks off it can quickly travel to the brain, get caught and cut off the circulation to part of the brain. This is a type of stroke, and is a huge problem for people with atrial fibrillation.

There are people who like to refer to a stroke as a “brain attack” because that’s what it is – like a heart attack in the brain. And like heart attacks there are big ones and small ones. I had a small one (TIA – tangent ischemia episode) that fortunately only lasted a minute or so. A big stroke, of course, can be fatal.

Important point: if a person is in atrial fibrillation and has blood clot in the LAA, it might be very stable. It might be just sitting there, hanging out, because the atria isn’t doing any beating. Everything is pretty tranquil in there. But then the person has a cardioversion (shock to reset the beating heart) or an ablation and the atrium begins to beat again, the blood starts moving through more quickly – well – now there’s a problem. Now the clot can break loose and BLAM!! – you’ve had a stroke!

The problem: it’s difficult to tell whether or not a patient has a clot prior to having a procedure. A regular echocardiogram doesn’t even show a small clot; there’s not enough detail. The best way to determine if a clot is present is to do a transesophageal echocardiogram (TEE).

teeTransesophageal Echocardiogram

I’ve had three TEEs – it’s not fun – sort of like swallowing a telephone. Thankfully the last two that I had involved an anesthesiologist who put me to sleep for the procedure.

As far as I know it is fairly common to have a TEE prior to having an ablation procedure; but less common before a cardioversion (the shock!), especially for people who presumably have a low risk of a LAA blot clot – like people who are appropriately anti-coagulated, or people who have had atrial fibrillation for less that 48 hours.

In this article five interesting cases are reviewed.

Case #1 – a patient who was effectively anti-coagulated but turned out to have a LAA clot anyway (sounds familiar).

Case #2 – a patient who was actually more anti-coagulated than thought necessary, and was in atrial flutter for less than 48 hours, but turned out to have a LAA clot anyway.

Case #3 – an appropriately anti-coagulated person with a low risk of clot (CHADS2 score=1), but turned out to have a LAA clot anyway.

Cases #4 and #5 were high risk patients who would be expected to have a high risk of a clot. Case #5 actually had three clots in her heart – yikes!

How does all this apply to athletes with atrial fibrillation? Well, apparently healthy, athletic patients, who are appropriately anti-coagulated, and either undergoing a planned or emergency cardioversion, still have a certain risk of having a LAA clot and subsequent stroke.

Should everybody have a TEE before having a cardioversion? Probably not. TEE is expensive, unpleasant, and if anesthesia is involved it basically takes up an entire day out of your schedule. It might be a good idea to talk it over with your cardiologist, however.

mooreparkrun
Happy Trails

afibrunner.com – Healthline’s The Best Atrial Fibrillation Blogs of the Year

afib-best

I’m going to “ring my own bell” here and post that afibrunner.com has been chosen, once again, as one of Healthline’s The Best Atrial Fibrillation Blogs of the Year. Thanks so much, Healthline!

According to my WordPress dashboard I have a lot of views of my blog directed from healthline.com – I truly appreciate it.

Please feel free to leave comments on this blog.

Update Part 2 – Atrial Fibrillation, Pradaxa Fail, Transient Ischemic Episode, Blood Clot in Left Atrial Appendage

Jimi Hendrix sang, “manic depression’s a frustrating mess.” Well, I think the same can be said of atrial fibrillation!

mountainbikingwringoRingo and Me – Photo by Ben Vallejos

It’s been a while since I have written and I have to say the last couple of months have been nerve-wracking. As I posted in a previous entry I had a TIA (transient ischemic attack) while running a couple of months ago, had a normal carotid scan, but a TEE (trans-esophageal echocardiogram) showed that I had a small blood clot in my left atrial appendage.

In other words I had a “mini-stroke” and was at risk of having a full on stroke.

pradaxa

This TIA occurred while I was on Pradaxa, a newer, novel anticoagulant. At that point I was taken off Pradaxa, started on Lovenox (low molecular weight heparin) injections, and warfarin (Coumadin), and also aspirin. I was instructed to discontinue running, and bicycling, and limit my activity to easy walks, and a repeat TEE was scheduled two months after the initial one.

I won’t hold back any longer regarding the surprise ending – I never had a second TIA “mini-stroke” (that I know of) or stroke and the follow-up TEE (trans-esophageal echocardiogram) showed that the blood clot inside my heart is now gone. Hooray!

appendagePhoto – The little cul-de-sac is the LA appendage

Just to review how this happens: when you are in atrial fibrillation your atria is beating so fast it’s like it isn’t beating at all, just sort of vibrating. There is a part of the left atrium (the “appendage”) where the blow flow is extra sluggish, and this is where clots can form. When a tiny piece of clot breaks of and goes into the brain that’s a TIA. If a big clot is present and breaks of into the brain that’s a stroke, which of course can be disabling and even fatal.

It goes without saying that I am disappointed that this occurred while I was on Pradaxa. I figured that as long as I was taking it I was safe, and I liked not having to watch my diet or have blood tests constantly. Taking Pradaxa is easy – “set it and forget it.” Now I’m on warfarin (Coumadin), a royal pain in the butt, and have to micromanage my diet constantly – this drug is not an easy choice for a vegetarian! Eating too many greens (think kale) is dangerous as is not eating enough greens. Imagine trying to eat about the same amount of kale or broccoli or spinach each day.

zaPhoto – vegan pizza

My target INR is between 2.0 and 3.0, but seeing as I have had a TIA while on an anticoagulant I am trying to keep it nearer to 3.0 or even higher (3.0 – 3.5).

The two months between echocardiograms was an era of angst – anxiety and fear – for me, especially the first several weeks. Every symptom, no matter how minor, seemed like stroke. For example – lie in bed trying to get to sleep and your hand becomes numb – normal, right? Not when you know you have a blood clot in your heart – that seems like a stroke! Jump up from bed, start testing the muscle strength in each arm and leg, recite the alphabet, smile, frown, move eyebrows up and down checking for asymmetry. Do you think I’m exaggerating?

Every once in a while a person stammers or mispronounces a word. Normal? Maybe, but not when you are obsessed with a gigantic blood clot lodging in your brain.

As far as exercise was concerned at first I was limiting myself to short, easy walks more appropriate for a non-athlete. Eventually I became a bit bolder and started doing longer (but slow, especially up hills) hikes of an hour or two. It took me three weeks (!) to bridge to a therapeutic INR, so I was on warfarin and Lovenox for all that time. Once I was off the injections I started doing bike rides – but they were on non-technical trails and were slow, especially while going uphill.

My brain never got the memo that I was no longer a long distance runner/cyclist so I still ate like I was, and consequently I’ve gained some weight.

At this point, after finding out the clot is no longer present, I have started increasing the intensity of my bike rides, but mostly I’m still doing bike rides. I haven’t yet started running again – but I will.

I am mountain biking again, but not on any trails that would be considered challenging. Well, that’s not 100% true, I guess.

awol-1-2Photo – “Adventure Without Limits?”

As far as mountain biking is concerned I am phasing out technical trails (gradually). I made a deal with my self that if I didn’t have the blood clot on the second TEE I would get a new bike – and I did. I got a Specialized AWOL, which is a “gravel grinder.” That’s sort of a cross between cyclocross bike and a loaded touring road bike – basically a bike designed for gravel or dirt roads – we have an infinite supply of these around here so I have a lot of exploring ahead of me.

As far as that blood clot is concerned I’m very pleased it has gone away – but I am not fooling myself that it is gone forever. It could return at any time. It wasn’t there when I had my second TEE, but it could actually be there right now – how would I know? How long had it been there and how many times have I had a clot in that area? There’s no telling without doing a ridiculously expensive, somewhat invasive test over and over. I guess all I can do is stay vigilant, take my meds, watch the diet, and keep on trying to run, hike, and ride, even if it is at a reduced level.