Warfarin Phased Out by Next Generation Agents?

March 5, 2014 7:54 AM

Warfarin, for decades the standard of care for stroke prevention in patient with atrial fibrillation, has met its match! Novel oral anticoagulants are the new standard of care, with a favorable efficacy:safety profile compared with warfarin. And what’s more, they don’t require regular monitoring like warfarin.

But not everyone is cheering. John Mandrola, MD, offers some perspective on the relative risk reductions shown by the new drugs vs warfarin (free reg required). And a recent lawsuit alleges that Boehringer Ingelheim withheld unfavorable data on fatal bleeding, the most feared adverse event for patients on chronic anticoagulation. FDA is also taking a second look at bleeding associated with BI's Pradaxa (dabigatran).

But in the end, it is the death panels payors who will decide the fate of these drugs, based on the total cost of medical care associated with their use. And right now, apixaban, rivaroxaban, and dabigatran are looking good, with an advantage in overall annual expenditure per patient driven largely by reduced costs associated with hemorrhagic stroke.

posted by Mister_A (33 comments total)

hey, maybe that will kill the long lines at the lab I go to for bloodwork/xrays etc. It's the 80 folks coming in for their coumadin treatment that fill the waiting room, lobby, hallway etc.
posted by k5.user at 7:56 AM on March 5, 2014 [1 favorite]

A quick note about the John Mandrola article. You need a MedScape account to access it from the link above, but for some reason, if you do a google search for novel oral anticoagulants vs warfarin you will see the article listed, and you can click through. It's called "Novel Oral Anticoagulants vs Warfarin - The Truth Is Relative."
posted by Mister_A at 7:56 AM on March 5, 2014 [1 favorite]

Important to point out that warfarin is just one of many products whose patents help fund the University of Wisconsin via WARF. And the patents under dispute in WARF's lawsuit against Apple could be worth billions.
posted by escabeche at 7:57 AM on March 5, 2014 [7 favorites]

k5.user: "hey, maybe that will kill the long lines at the lab I go to for bloodwork/xrays etc. It's the 80 folks coming in for their coumadin treatment that fill the waiting room, lobby, hallway etc."

Some places have dedicated "coumadin clinics" for the warfarin patients; bummer that you don't in your area.
posted by Mister_A at 7:58 AM on March 5, 2014

These days everyone's a coumadin.
posted by Potomac Avenue at 7:59 AM on March 5, 2014 [2 favorites]

Metafilter: Worf, WARF, and Warfarin... We Got 'Em Covered
posted by DirtyOldTown at 8:00 AM on March 5, 2014 [2 favorites]

Most of these newer agents don't have a specific antidote or antagonist to reverse their anticoagulation effect, which can mean substantially more bleeding if you need urgent or emergent surgery.

Coumadin is a terrible drug, but at least you can give fresh frozen plasma and vitamin K to reverse most of its effects pretty fast if need be.
posted by etherist at 8:02 AM on March 5, 2014 [6 favorites]

with an advantage in overall annual expenditure per patient driven largely by reduced costs associated with hemorrhagic stroke.

"A cost comparison analysis was conducted from the US perspective."

So these drugs may not be so effective if you take them in other countries.
posted by three blind mice at 8:05 AM on March 5, 2014

Most of these newer agents don't have a specific antidote or antagonist to reverse their anticoagulation effect, which can mean substantially more bleeding if you need urgent or emergent surgery.

Exactly this! I have had relatives endangered by injuries after taking non-coumadin blood thinners. Surgeons can't operate, and internal bleeding can be very nasty. With coumadin, you can at least reverse the problem and operate, or get the bleeding to stop.
posted by blahblahblah at 8:06 AM on March 5, 2014 [4 favorites]

I see what you did with that headline.
posted by Eyebrows McGee at 8:07 AM on March 5, 2014 [17 favorites]

Who, me?
posted by Mister_A at 8:08 AM on March 5, 2014 [4 favorites]

I get a chuckle out of that commercial with the guy on warfarin wondering if he could "do better". If you're taking a drug and the side effects aren't horrible I'm betting you don't even think about it, let alone wonder if you could do better on something else.
posted by tommasz at 8:26 AM on March 5, 2014 [1 favorite]

And all this convenience for only hundreds of thousands of dollars a year!

Well, at least the last time I checked the prices of the new wonder drugs. Warfarin isn't going away anytime soon.
posted by hobo gitano de queretaro at 8:32 AM on March 5, 2014 [1 favorite]

I get a chuckle out of that commercial with the guy on warfarin wondering if he could "do better".

Isn't there a similar commercial where the middle-aged guy wonders if he couldn't "up his game", right before going out to shoot hoops with his adult son?
posted by Thorzdad at 8:33 AM on March 5, 2014

Many of the newer anticoagulants are factor Xa inhibitors, there are a few fXa analogues being developed that bind these anticoagulants which would make them much safer.
posted by atrazine at 8:36 AM on March 5, 2014 [1 favorite]

I can still poison rats with Warfarin though, right?
posted by Ham Snadwich at 8:37 AM on March 5, 2014 [5 favorites]

If you're taking a drug and the side effects aren't horrible I'm betting you don't even think about it, let alone wonder if you could do better on something else.

My father just had to start using coumadin, and it sucks. There is definitely a large "it's 2014! why am I eating rat poison and getting blood drawn every few days and can't eat spinach anymore?" aspect to it.

You end up spending a lot of time waiting around in the aforementioned 'coumadin clinics' for blood draws, and then waiting longer for them to call you back with dosage-change instructions (or not, because sometimes they just don't call you, and then you find out later that you were ODing and maybe flirting with bleeding to death for a while, whoops sorry), and trying to figure out what foods you can eat and which you can't because they screw with the drug, and building your travel/vacation schedule around it, etc. And that's setting aside the actual side effects and more legitimate medical risks.

Particularly when you compare it to how advanced and high-tech everything else related to modern cardiac care feels, from a patient's perspective coumadin/warfarin therapies feel like one small step away from drinking radium water circa 1920.
posted by Kadin2048 at 9:02 AM on March 5, 2014 [1 favorite]

Metafilter: Worf, WARF, and Warfarin... We Got 'Em Covered
posted by DirtyOldTown at 11:00 AM on March 5

You forgot wharf!
posted by ssmug at 9:03 AM on March 5, 2014

... and warfare.
posted by JoeXIII007 at 9:34 AM on March 5, 2014

I get a chuckle out of that commercial with the guy on warfarin wondering if he could "do better".

Actually I think that's pretty realistic for patients on warfarin. It's a deeply scary situation to be in. You constantly know you're walking the line between brain injury and early death from clots caused by the condition that put you on the drug, and brain injury and early death from hemorrhaging due to the drug itself.

Many or most patients make fairly substantial lifestyle changes in order to make it easier to stay on the peak between those two valleys. A drug that makes management easier or more consistent means more years of full functioning and more years of life.

I think it's important to note that these new drugs are not a warfarin replacement for all patients. In particular, my understanding (IANAMD) is that the FDA has concluded that none of them is appropriate for people with mechanical replacement valves and AF caused by valve defects.
posted by CHoldredge at 10:01 AM on March 5, 2014

For those interested there is a good summary of some of the problems and strengths of the newer drugs--from the point of view of a "hospitalist". Also a good summary of the progress being made in developing hospital protocols and agents for reversing the new drugs. Upsides/downsides. Almost always the case. Moderately long read.
posted by rmhsinc at 10:47 AM on March 5, 2014 [1 favorite]

This is also not for everyone, but I emphatically recommend that anyone with a-fib investigate the procedure called catheter ablation. Success rates (as in cure) are high, and the procedure often does not require even an overnight hospital stay. I had it done, and if the a-fib should return, I'll have it done again. Not having to do Warfarin is a major benefit.

Your cardiologist may not tell you about ablation. Mine didn't - I had to ask. So ask.
posted by Kirth Gerson at 11:10 AM on March 5, 2014 [1 favorite]

I've been on Xarelto for about 6 months. I get lots of questions from doctors about it when they find out, they are almost always curious. Its been great for me and from what I understand from Warfarin, much easier to deal with.
posted by Bovine Love at 11:10 AM on March 5, 2014

My father-in-law died a few years ago after catheter ablation of his A-fib.

He had a stroke during or just after the procedure and it wasn't recognized promptly. He never really regained consciousness and died 5 days later.

So ask your cardiologist about it, but also ask what is the incidence of complications in general, and ask what is their personal rate of complications. Any strokes? Any deaths? Any perforations of the heart muscle? Worsening of the arrhythmia? Shop around.
posted by etherist at 11:41 AM on March 5, 2014 [2 favorites]

Coumadin is a terrible drug, but at least you can give fresh frozen plasma and vitamin K to reverse most of its effects pretty fast if need be.

My dad died last year after a very minor car accident because the coumadin in his system caused an unstoppable bleed in his brain, so clearly not fast enough for my taste!
posted by The 10th Regiment of Foot at 12:32 PM on March 5, 2014

I can still poison rats with Warfarin though, right?
You waited too long. A pharmacist told me that it would take gallons of warfarin since rats are now mostly immune.
posted by Cranberry at 1:08 PM on March 5, 2014 [2 favorites]

A pharmacist told me that it would take gallons of warfarin since rats are now mostly immune.

It also screws up my plan to slowly kill my rats with artery clogging cholesterol.
posted by The 10th Regiment of Foot at 1:23 PM on March 5, 2014 [2 favorites]

I've been on Coumadin for a year now. I was absolutely terrified of going on it, almost more so than the surgery itself. Really just sick about it. And I'm here to say that my fear was wildly overstated, and Coumadin has been absolutely nothing to take. It's a pill I take before bedtime, and then once a week, I prick my finger and get my INR and call it in. And it's never really been outside of my target range.

I'm a vegetarian. I eat spinach/kale/edamame/cauliflower in like bulk epic quantities every single day. I drink wine by the bottle. It doesn't matter. I will say that I am consistent in my intake-- WHICH IS THE KEY-- and I eat copious amounts of vitamin K. I've cut myself, I've bled, I've used bandaids and it's stopped. My target INR is rather low, though.

I'd love to talk to anyone who is fearing a Coumadin regimen. I cannot believe I wasted so much energy worrying about it. It really has been a negligible difference in my life. I remember crossing my fingers and thinking they'd invent something to replace it- and it looks like they are trying- but given how incredibly easy it's been, and how there's a reliable and ready antidote should I need it, I can't really imagine making a switch.
posted by xmutex at 5:50 PM on March 5, 2014

So ask your cardiologist about it, but also ask what is the incidence of complications in general, and ask what is their personal rate of complications.

My recollection of the research I did at the time is that the overall rate of complications is very low, and that it drops steeply (and the success rate goes up steeply) after a given surgeon has done five of the procedures. So you want an experienced doctor.
posted by Kirth Gerson at 6:09 PM on March 5, 2014

What scares me is for some of these drugs, like Xarelto, there's no antagonist. If you are on Coumadin and need surgery, you get vitamin K (and admittedly wait many hours just to be safe). If there's no antagonist, you simply have to wait until the drug is out of your system. I think I saw an estimate of 24 hours for Xarelto. If you're hemorrhaging, that may be too long.
posted by IndigoRain at 7:23 AM on March 6, 2014

As explained by my thrombosis doctor, Xarelto blocks Xa for 12 hours, and then it takes about another 12 hours for Xa to to return to normal so yea, basically 24 hours after the last dose.

When I asked about injury (not internal haemorrhaging, now, external injury which I am inclined to), he said they could administer one of those anti-bleeding treatments if it were really bad, but of course it would be painful. My only 'regular' activity they advised against was downhill skiing. That would not apply to internal bleeding, of course.

On *my* level, I've cut myself a few times, and the bleeding was not severe. Dentistry proved to be a bit problematic, and they asked if I could be off it next time I return. I'm likely to be off it soon anyway (idiopathic thrombosis, they seem to feel continued dosing is not worth it), so its ok. Of course, dosages, and outcomes vary. I'm not sure what would happen on serious internal bleeding. I've had a couple of instances of minor internal bleeding on it, but luckily not bad.
posted by Bovine Love at 7:37 AM on March 6, 2014 [1 favorite]

My dad recently passed away from congestive heart failure combined with a-fib. He was on coumadin. Tried predaxa but forgot the reason why they stopped it. As his condition was worsening, it came to the point in talking with the cardiologist--would you rather him have a debilitating stroke and live or bleed out from a fall? As harsh as it sounds, when you start to come to end stage disease, quality of life starts to be the precident. So we all decided bleed out is a better way to die. But he was falling so much that the other docs said "oh no, stop the warfarin and let him get a stroke." By the time hospice interviened we agreed that by this time, his heart is so bad that honestly, he wasn't going to make it to a stroke anyway. He didn't.

The entire cardiac experience for him during that time was nothing but a pain in the ass---coumadin levels checked, cardiac visits, and weekly CHF clinic visits on top of emergency in patient hospitalizations. If you're in that state, I don't think any drug--good or bad side effects--matter.
posted by stormpooper at 8:52 AM on March 6, 2014

would you rather him have a debilitating stroke and live or bleed out from a fall?

When my dad was dying in the neuro-ICU my family all agreed that without the coumadin we would likely have been standing around him dying in the cardio-ICU down the hall.
posted by The 10th Regiment of Foot at 10:49 AM on March 6, 2014