Higher Rates of Stroke with Eliquis vs. Warfarin?

I stumbled upon this study and it says that stroke rates were greater with Eliquis than with Warfarin. I thought all the studies showed just the opposite...that Eliquis was actually just as good if not better than Warfarin in preventing strokes. Is my memory wrong on this or is this an outlier study?

[www.clinicaladvisor.com]

Travis

Travis, Hopefully Shannon will get this cleared. According to the link, the study was for 2.5 mg twice daily. Dr. Natale has me on 5mg twice daily which is the dose his patients start at I think. I remember also that the studies show Eliquis better than Warfarin. Eliquis sure is a lot easier to take, but more expensive.

...ronH

Travis,

This is a misleading headline ... Eliquis was compared only with its half dose 2.5 mg strength compared to its 5mg full dose strength which is a full double size larger than the 2,5mg. And this is then compared relative to 15mg of Xeralto where its full dose strength is only 20mg with the lower dose being 75% as strong as the recommended full dose of 20mg. And a similar mismatch is used in comparison of Eliquis relative to Pradaxa using the 110mg lower dose strength of Pradaxa which is still higher than one half the normal 150mg strength of Pradaxa as prescribed for non-valvular AFIB.

The vast majority of folks with normal kidney function will get Eliquis at the standard dose of 5mg for AFIB. The use of lower dosing is usually reserved for folks with impaired renal function and/or those deemed at significantly reduced overall stroke risk.

It's late and Im shutting of the light for bed, but will examine who did this study and what their angle was over the next few days. At the end of next week I will be at the ISLAA conference being held this year in Austin, and everything LAA and OAC will be discussed in great nuance.

Eliquis is still the preferred member by the majority of EPs of the DOAC (or NOAC) family of new non-Vitamin K oral anti-coagulants. Certainly, it is the most preferred that the vast majority of EPs I know of, and as reported at all the conferences of the last three years since Eliquis hit the market.

That does not mean that one is immune from an embolic event while on any dose of these new DOACs ( Direct Oral Anti-Coagulants), even the full recommended AFIB dose of 5 mg for Eliquis, 20mg Xeralto and 150mg Pradaxa, while at least non-inferior in stroke risk to Warfarin, they are not risk-free for having an embolic stroke and its also possible to have a hemorrhagic stroke on all these drugs or serious GI bleed as well.

It is all about weighing the risk/benefit for the right patient, but there is no ZERO risk scenario for any dose of OAC, including obviously Warfarin.

And Travis, I would not post this particular article on your blog, as the way it is written is likely to create more misleading confusion than clarity. The full British Medical Journal Study which is well done, tells the more accurate story with a better delineation and distinction between the low dose NOAC therapy required for folks with impaired renal function that this study is based on, and the far more typical full standard dosing for each of these NOACs that the vast majority of Afibbers take who require OAC therapy to begin with, though it may well be too technical for many to want to wade through the full study. Perhaps there is another such online medical or cardio news site that is also summarizing this study that might make it more clear that the typical full dose of Eliquis is completely and favorably comparable to the other NOACs at their typical full dose size too as well as with Warfarin as well.

Thanks for letting us know about it though as it will be interesting to follow the future nuances of low dose NOAC therapy. At the latest AF Symposium 2017 in Orlando there was discussion of the drug makers coming our with additional dosing sized to accommodate different needs and I could see where the makers of Eliquis might be inspired to offer the 3.75 mg dose which is 75% of the full 5mg dose and that would be a directly and precisely a better apples to apples comparison with Xeralto's and Pradaxa's low dose offerings.

Cheers!
Shannon

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PS Folks,

It is now Wednesday morning and I just read through the full British Medical Journal Study that the 'Clinical Advisor' article Travis linked to above had summarized.

There is no reason elicited in this study for the typical AFIB patient prescribed Eliquis to switch to either Xeralto or Pradaxa based on the full article findings! And certainly not simply based on the results that indicate a 'non-significant' increased risk of a low 2.5mg BID (BID = twice a day) dose of Eliquis vs within INR range warfarin, and taking into account that the standard full Eliquis dose for AFIB is 5mg BID.

Note too, that the low 2.5mg Eliquis dose is a full 50% weaker than the full 5mg dose prescribed for nearly all Afibbers except those with some combination of being >/= 80years old with an impaired renal function and/or with a weight </= 60kilograms.

The lowest 110mg Pradaxa dose is 73% as strong as the full 150mg Pradaxa dose, and for Xeralto the 15mg lowest dose is 75% as strong compared to the 20mg full standard dose. Just comparing these three drugs low dose strengths would indicate a possible rationale for the slightly larger increase risk of embolic events shown at 1 years and 2.5 years follow up on this admittedly large size (55,644 and the Scandinavian registry studies are renowned for the consistently solid data due to the great record keeping of the full population's health history in these countries) of older patients all of whom had at least two of the three criteria for prescribing the lower dose of each NOAC: Older age >/= 80 yrs old, a poor renal function and/or underweight at </= 60 kilos.

So, it's important when considering the three NOACs to realize that this 'non-significant' increase in embolic events relative to Warfarin and only slight increase relative to either Pradaxa's lowest dose of 110mg BID vs the standard 150mg BID dose, or Xeralto's lowest dose of 15mg once a day vs. the standard 20mg once a day dose, would only potentially apply to a relatively small number of Afibbers to begin with and not at all to the vast majority of those taking 5mg BID dosing of Eliquis due to risk scores that qualify one for OAC therapy and who still have decent renal function.

Plus, when reading the full study several other possible contributions to a higher 'appearing' embolic stroke/TIA risk are apparent for the group taking the 2.5mg low dose Eliquis vs. the low dose of the other two NOACs, could be due, in part, to such factors as a 4 year average older age at 83.9 years old for the Eliquis cohort vs 79.9 years for Pradaxa and and 77.9 years for Xeralto so ranging from 4 to 6 years younger patients than is the Eliquis group, respectively, in the Pradaxa and Xeralto groups. This clearly older age cohort taking 2.5mg of Eliquis could influence such factors as systemic stroke risk and other co-morbidities as well as all cause mortality.

Plus, the low dose 2.5mg BID Eliquis group had a higher incidence of prior stroke/TIA and higher number of co-morbidities leading to an overall higher CHA2DS-VASc risk scores than those in the other two NOAC groups.

In any event, this is a good study looking at these special risk patients who require a reduced dose of any blood thinner that is processed largely, or in part, via adequate renal function. But at this point this observational registry study is only 'hypothesis generating', meaning that it points to the need for more in-depth and focused studies comparing these lower dose alternatives to the full standard dosing of Eliquis, Pradaxa, Xeralto and also Edoxaban.

However, it bares emphasizing that this study in NO way suggests anyone who is taking especially the standard 5mg dose Eliquis should suddenly demand switching to one of the other NOACs based on the results from this one analysis.

What this study may indicate, in addition to the need to conduct further more apples to apples comparison studies of these low dose versions of all the NOACs in people who need a lower dose, is the possibility that the makers of Eliquis may want to offer a 3.75mg dose of the drug too ( which is 75% the strength of the full 5mg dose) to give doctors and patients even more flexibility in dosing Eliquis on an individual basis while offering a dose that clearly compares favorably to the lowest dose of Xeralto's at 15mg and Pradaxa's 110mg low dose offering.

As for those special cases who have been prescribed a 2.5mg Eliquis dose after having LAA isolation, and who were found to have a borderline okay LAA mechanical function as confirmed after one or more 6 month TEES post LAA isolation, Dr Natale will only have prescribed the 2.5mg dose to those whose mechanical function passed with flying colors on at least two of the three screening criteria on TEE for possibly earning the right to avoid OAC long term, but in which one of the three criteria may have been slightly borderline low.

He would only offer the 2.5mg dose, too, when the patient had a reasonably low stroke risk score with minimal systemic CVD co-morbidities, plus when they had no impaired renal function as well .. and this is a special situation as well that is not reflected in the study results above relating to low dose Eliquis.

I hope this clarifies the issue, and underlines why I found the 'Clinical Advisor" summary article about this interesting Danish registry study a bit misleading by not emphasizing the inapplicable nature of the results when comparing standard full size recommended AFIB dosing of all the NOAC drugs used by folks with decent renal function, either compared to each other or to Warfarin.


Take care,
Shannon



Edited 2 time(s). Last edit at 02/23/2017 12:42AM by Shannon.

So, based on that, should I insist my EP's office switch me from Xarelto to Eliquis? I've been on Xarelto for a couple years with no problems and when I bring up this bias towards Eliquis the response is that if I'm stable on Xarelto then why switch.

Hi PBqltbook,

Please reread my reply just above your own and in particular the new last half that I added this morning to find answers to your question and a bit more insight into the special focus and value of this Danish study comparing low doses of all the major NOACs to each other and to Warfarin with either octogenarian's or even older folks and/or those with impaired renal function.

There is no huge rush to switch to Eliquis from a well-tolerated Xeralto or Pradaxa, other than Eliquis shorter half life than Xeralto has some advantages in terms of lessening major complications from an emergency major bleeding event due to the shorter effective time Eliquis is active in the body before one's endogenous clothing factors start to kick in again after the last dose of Eliquis versus the last dose of Xeralto, were it taken at the same time frame.

Most EPs prefer Eliquis too for its low practical bleeding risk during ablation, but the others can work okay as well. The key is making sure, if your are on Eliquis or Pradaxa that you take BOTH doses each day and not skip any doses!

Also, keep in mind that a relatively rare, but not Zero, risk of having even a significant stroke exists, and has happened, with all four of the NOACs even when taken regularly, but that is still quite rare.

We still don't fully understand what the mechanism is behind these very unfortunate embolic events while taking a blood thinner normally .. the same is true too, though likely from a different mechanism .. for warfarin and the ongoing risk for thromboembolism, even when INR is maintained largely within the therapeutic range.

Thus, we need to emphasize that while these drugs can and do offer a major risk reduction for stroke in those who clearly can benefit from OAC therapy, they are not absolute solutions for eliminating all embolic event risk, by any means, and they all carry additional bleeding risks too that are not often found in the absence of the drugs. Again, its all about matching the risk/ reward equation that is still a bit of an art form too. It is also where the advances being made in LAA Closure devices and improved techniques offers a real asset as a key part of a comprehensive stroke risk reduction effort, including the possibility of all but eliminating all OAC-induced bleeding risk as well as the vast majority of all AFIB/LAA-related embolic stroke risk.

Shannon



Edited 1 time(s). Last edit at 02/22/2017 03:25PM by Shannon.

I will be swapping from Eliquis to Xarelto in March. This is because Eliquis is the more expensive blood thinner by far on My Medicare part D plan. Also, Optma RX sent me a letter a letter last week saying I should consider swapping to Xarelto or Pradaxa.
Optima RX was my former prescription drug plan before I became out of necessity Part D on Medicare.
It seems that Eliquis was not willing to negotiate. Both will put me in the " donut hole" but Xarelto and Pradaxa is $42 a month whereas Eliquis is $166 a month. Eliquis went from a Tier 3 drug to a Tier 4 drug on at least 5 Medicare Part D plans I checked for 2017.
Highway robbery

I have been on xarelto for over 2 years. If you have insurance, xarelto offers a care plan where they pay for everything after the insurance company pays their portion. Therefore I have been paying 0$ for my monthly prescription.

Quote
amyorca
I have been on xarelto for over 2 years. If you have insurance, xarelto offers a care plan where they pay for everything after the insurance company pays their portion. Therefore I have been paying 0$ for my monthly prescription.

Does not work with Medicare

Thanks for the detailed explanation, Shannon. I didn't post that article on my blog because I thought it was very misleading as well (which is why I posted it here for clarification). I also didn't catch the low dose part of the study. I thought they were referring to the usual 5mg 2x daily dose of Eliquis.

At any rate, it's all cleared up now

Have a good one!

Travis

Dr Natale told be stay on Xarelto and not switch to Eliquis after my 2nd touch-up ablation with him....well it was more extensive then touch-up!
I now have low flow velocity from my LAA but afib free.

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McHale
Dr Natale told be stay on Xarelto and not switch to Eliquis after my 2nd touch-up ablation with him....well it was more extensive then touch-up!
I now have low flow velocity from my LAA but afib free.

Hi McHale, the last sentence too is the best bargain too! If you have LAA triggers and it is never addressed, you WILL have low flow velocity from your LAA the entire time you are in AFIB ... and as it almost inevitably become persistent and LSPAF over time when ones condition has evolved to include migration of the triggering to the LAA as the last frontier area of the left atrial to sustain and arrhythmia, that means 24/7 low flow from the LAA as well.

Same is true in frequent paroxysmal AFIB too, as mechanical function of the LAA is most often impaired as well when one is in AFIB.

If one has to trade having low flow from the LAA which most all would have anyway with LAA triggering present during persistent or ver frequent PAF, it is sure a handy lottery win to be free of AFIB in the bargain!!

Also, Dr Natale does not prefer Xeralto over Eliquis for most people, but if someone comes to him on Xeralto who expresses a wish to stay with it, unless he thing s they should switch, he is fine to keep prescribing Xeralto. The two drugs are more similar than different.

Be well,
Shannon