Which "Blood thinner"

I Have Atrial Fibrillation: Which New Blood Thinner Should I Take?

By T. Jared Bunch, MD

Published Nov 19, 2013

Today at the American Heart Association meetings in Dallas, the results of the Engage AF TIMI 48 trial were presented. This was a large trial that essentially evaluated a new drug therapy to prevent stroke in patients with atrial fibrillation.

Atrial Fibrillation and Stroke

Atrial fibrillation is an abnormal heart rhythm that results in loss of active squeezing of the upper heart chambers. As such, blood flow slows and clots can form. These clots can then be injected to the body organs, and if they go to the brain a stroke develops.

Stroke Prevention

For many years, one drug was the proven therapy for stroke prevention in patients with atrial fibrillation. This drug is called warfarin (Coumadin). Warfarin is an anticoagulant or blood thinner. The drug doesn’t actually make the blood thinner; it makes it less likely to form a clot. Warfarin works by blocking our body’s ability to recycle vitamin K. Vitamin K is used in many of the small proteins that come together to create a clot. With less vitamin K around in our bodies, there are less of these proteins available and as a consequence it takes the body longer to form a clot.

Warfarin is a tough drug to take long term. In previous studies around 30% of people will stop taking it. It requires frequent blood tests to regulate the dose. Warfarin also has many interactions with other drugs, herbs, and food sources. Diets often are modified to minimize the amount of vitamin K consumed and make the drug’s effect in the body more predictable. For over 20 years there has been extensive efforts to replace warfarin with other drugs. Many drugs have come and gone as they were either not as effective or were more hazardous than warfarin. Over the past 3 years new safer drugs have emerged. These drugs are called novel oral anticoagulants (NOACs). Where we have not had good alternatives for warfarin in the past, we now have 4 that have come available all in a short period of time. This is a great benefit for patient care, but at the same time it leads to confusion as to which drug should be used.

Novel Oral Anticoagulants

The new drugs are called dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Lixiana). The trade names are those in parenthesis. Edoxaban was the most recent drug studied and was the subject of the Engage AF TIMI 48 trial (4).

First, your insurance provider will have a direct say into which drug you take. One or two of these new drugs may be approved for your use. In this regard, realize that all of these drugs are at least as good as warfarin for preventing stroke and all are better than warfarin in reducing your risk of serious bleeding in the brain. All of these products are not reversible, similar to warfarin, and if you are bleeding the use of blood products and other measures may be required to help your body stop. However there are some important differences to consider.

Dabigatran (Pradaxa) was the first drug that was available in the United States. Dabigatran comes in two doses in the United States, 150 mg twice daily or 75 mg twice daily. Dabigatran was not only equal to warfarin, but it proved to be superior to it in preventing stroke in the RELY trial (1). Bleeding rates in the head were lower with dabigatran. However, bleeding from the stomach or bowels was higher. The most common side effect was dyspepsia, which is a term used to describe stomach pain. Dyspepsia was relatively common occurring in approximately 11% of people. The lower dose available in the United States is for people that have moderate kidney dysfunction. It is important to know that the lower dose was not formally used in the RELY study. Without a large body of clinical evidence to support the use of the lower dose and understand potential risks, I do not use it.

Rivaroxaban (Xarelto) was the second drug available in the United States. Rivaroxaban comes in two doses, 20 mg daily or 15 mg daily. In the Rocket AF trial, rivaroxaban was at least as good and tended to be better than warfarin at preventing stroke (2). Rivaroxaban also significantly lowered the risk of bleeding in the brain and head. Bleeding in other locations was slightly higher with rivaroxaban compared to warfarin. The lower dose is for people that have moderate kidney dysfunction. This dose was actively studied in the trial and found to be both effective and safe.

Apixaban (Eliquis) was the third drug to become available in the United States. Apixaban comes in two doses, 5 mg twice daily or 2.5 mg twice daily. In the Aristotle trial, apixaban was at least as good and tended to be better than warfarin at preventing stroke (3). Similar to the other drugs, risk of bleeding in the brain and head was lower. However, this drug was unique in that bleeding from other sites including the stomach, bowels, and bladder was less. Overall, apixaban due to better efficacy and lower bleeding improved survival significantly compared to warfarin. Apixaban is the only drug that can claim that survival improved with its’ use compared to warfarin. The lower dose is for people that have moderate kidney dysfunction. This dose was actively studied in the Aristotle trial and found to be both effective and safe.

Edoxaban (Lixiana) was the drug presented today and is not currently available in the United States. In the Engage AF TIMI 48 trial two doses were studied (60 mg and 30 mg daily) (4). This was a huge trial of 21,026 patients with follow-up of over 3 years in many patients. The higher dose of edoxaban was at least as good and tended to be better than warfarin at preventing stroke, however the lower dose was not as good as warfarin. Cranial or head bleeding was better with both the higher and lower doses of edoxaban compared to warfarin. Bleeding from the stomach was greater than warfarin with the higher dose of edoxaban and lower than warfarin with the lower dose of edoxaban.

Which Drug Should I Take?

Here are a few things to consider with attached recommendations.

If you have trouble taking drugs twice a day and often miss a dose, then you should use rivaroxaban or if it becomes available, the higher dose Edoxaban. Unlike warfarin these drugs quickly leave your body. You have to be very compliant with the dosing schedule or you will be at higher risk for a stroke.

If you have stomach pains or heart burn, then you should consider a drug other than dabigatran

If you are most concerned about stroke and less worried about bleeding then dabigatran was the only drug that was superior (not equal or slightly better) than warfarin in preventing stroke

If you are worried about bleeding or have experienced bleeding from the stomach, bowels, or bladder then apixaban is the better choice once you are cleared by your physician to use a blood thinner

If you want the drug that will, because of both its’ benefits and risks, help you live longer compared to warfarin then apixaban is your choice

If you have moderate kidney dysfunction then consider apixaban or rivaroxaban since these two drugs have reduced doses available that are well studied and found to be effective and safe

If you have used warfarin for years and rarely if ever have to change your dose and you have not experienced adverse symptoms then continue your warfarin.

I am hopeful with the many anticoagulation options in a competitive market the cost of these drugs will decline. As mentioned before, all of these drugs reduce stroke at rates nearly equal or better than warfarin and all reduce brain bleed risk. For the first time in decades, warfarin has significant competitors that will help us as physicians prevent one of the most devastating complications with atrial fibrillation, stoke.

21 Replies

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  • Very interesting article. Thanks for posting.

  • Thanks Carol

    Great article, if I do ever change from warfarin, and that day is becoming closer, then right now Apixaban would be my choice based on what I have read and the twice daily version.

    Ian

  • Hi Ian

    I have been taking Apixaban for 5 months now and think it beats Warfarin hands down. No blood tests, eat what you like within reason and blood stays thin. What more could one ask for lol!

  • A reversal agent?

    But it will come and it's increasingly attractive

    Be well

    Ian

  • I know the media marketing manager of Bristol Myers Squibb here in Australia and have been assured that their scientists are working overtime to come up with a reversal!

    Cheers

    Barry

  • IMHO (and this was my assessment for me for when I was on Apixaban) I don't think that we should be getting too worried about an antidote or reversal because of the short time that Apixaban actually remains in the system. I was told that it was largely ineffective after 24 hours but opinions do vary on that. I suspect that is why it has to be taken every 12 hours.

    In a normal situation, say leading up to an operation, you start warfarin and then once INR is up you stop Apixaban. For me the second blood test was only after 3 days though it could have been sooner.

    In a real emergency situation it will take longer to stop bleeding (rather than giving vitamin based antidote as with warfarin) but I understand that medics do have options for many situations. One has to then weigh up the many benefits of using Apixaban and the ease of use.

  • Very informative article Carol, thanks for that.

    If my day comes, I will refer to it.

    Pat.

  • Excellent article caromia, thank you for posting.

  • Thanks for posting this Carol - I've now decided, after reading this, that it would be Apixiban for me should I ever change from Warfarin. Would I have a choice of medication I wonder!! I know that my surgery like to prescribe Rivaroxaban.

  • Hi there Jean, good question re choice of NOACS. When it was suggested that I change to one because my INR was never stable on Warfarin, I requested Apixaban but was told by the anti-coag nurse that hospital policy was to prescribed Pradaxa. So I'm on that and it seems to be OK....they're doing kidney and liver function tests every 6 weeks and that will drop to every 6 months after a 6 month period.

    M x

  • Interesting but note the bit where he mentions that your insurance provider will have a say in what drug is prescribed.....

  • That's because it is for a US audience and the insurers pay for medications.

  • Yes, I know that! Don't get me started on insurance companies...

  • You started it! :-)

  • Only the bit about the insurance companies! I am anti because I have a congenital condition and I resent being penalised for something that isn't my fault.

    A good article but that point spoilt it for me. He should have stuck to the science. I suppose the equivalent UK point would be that you can have any drug that NICE deems to be cost effective.

    Happy with Rivaroxaban at present as it is once a day and I have concerns about kidney function.

  • My consultant EP put me on Apixaban because he said it was the best but now I am on Warfarin leading up to an ablation.

  • I have a watch alarm from Lloyds Better Life ( £12.99 if I remember correctly) which talks(!!) when my Apixaban is due. It is impossible to miss unlike some quiet alarms!!

    Just had a second blood test ,after first few months on Apixaban and, so far so good!!

    I thought this was an excellent article and very balanced in that he says if you've been very stable on Warfarin then stay with it. I've posted before about the difficulty if your surgery only do INRs infrequently- if you self test you can see if you really are stable by testing more often.

  • I have been ok so far on Rivaoxaban 2 years in Carol but I have not taken warfarin as I went straight onto a NOAC from aspirin. So far so good. I am sure you will make the best decision for you. Be well.

    Dee

  • In many cases the best solution may be to minimise fructose intake (which glycosylates haemoglobin seven-times as much as glucose) and replace it with natural fat.

  • Thanks Carol, found the information really interesting.

  • Why is it that people still insist that anticoagulaters are blood thinners they are not. They make the blood less sticky ( for want of another word) so that it pulses more readily.

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