Issue 5 / 15 February 2016

THE availability of novel oral anticoagulants has driven an increase in the overall use of anticoagulants and a shift away from warfarin towards the newer drugs, according to a study of anticoagulant use in veterans.

The retrospective observational study, published in this week’s MJA, found that in the year after the novel oral anticoagulants (NOACs) were listed on the Pharmaceutical Benefits Scheme (PBS) in 2013, there were 3936 new users of NOACs, and just 1506 new users of warfarin.

The authors said the overall increase in the use of oral anticoagulants since the introduction of NOACs might reflect the use in patients for whom warfarin was unsuitable.

They found that patients initiated on NOACs had fewer hospitalisations for gastrointestinal bleed (1.7% v 3.1%, P=0.0017), stroke (3.3% v 7.2%, P<0.0001) and myocardial infarction (2.2% v 4.5%, P<0.0001) when compared with patients on warfarin.

The authors noted that patients initiated on NOACs were younger, more likely to be men, had fewer comorbidities and were less likely to live in aged care facilities.

Professor Ross Baker, director of the WA Centre for Thrombosis and Haemostasis at Murdoch University, said it was interesting to note that around 70% of new prescriptions were for NOACs in the year after their PBS listing.

He said that even in this high-risk population – with a median age of 86 – there was less bleeding, stroke and myocardial infarction in the NOAC group compared with the warfarin group.

“There’s always the concern that there would be more problems in this [older] group. I think this means that in general practice we’re selecting the patients much better than we have previously,” Professor Baker said. “If you select the right sort of patients they do as well, if not better, [on NOACs] than on warfarin if they need antithrombotic therapy.”

Professor John Attia, professor of medicine and clinical epidemiology at the University of Newcastle, said the profile of patients initiated on NOACs suggested that these drugs were being used in patients with lower CHA2DS2 scores.

“If people are younger and have fewer comorbidities, their CHA2DS2 score would be lower. So, are these people who you wouldn’t normally start on anticoagulants because of the hassle?” Professor Attia said, adding that the findings should prompt clinicians to carefully evaluate the need for anticoagulants in patients with lower CHA2DS2 scores.

“These drugs are not without risk,” he said. “The CHA2DS2 score and the new version, the CHA2DS2-VASc score, are well validated tools to help us to stratify the risk – physicians need to use those tools to see if the risk is high enough to warrant starting somebody on these drugs.”

Of concern, said the study authors, was the co-administration of NOACs with non-steroidal anti-inflammatories (NSAIDs).

They found that 8.6% of patients on NOACs were also taking an NSAID [332/3819], compared with 6.2% of patients on warfarin [87/1397] (P<0.004).

“Together with the lack of reversibility of the anticoagulation effect of NOACs, these results are of concern and suggest that prescribers should consider the potential risks of bleeds when NOACs are co-administered with medicines such as [NSAIDs],” the researchers wrote.

Professor Attia agreed that the co-administration of NOACs with NSAIDs was cause for concern, particularly in the case of dabigatran, a combination he described as “dangerous”.

“It’s very concerning because there are a few things about dabigatran that people didn’t seem to pick up from the big randomised controlled trial that appeared in the New England Journal of Medicine,” said Professor Attia, pointing to the finding that dabigatran had a statistically significant higher risk of gastrointestinal bleed compared with warfarin.

Professor Attia said dabigatran also lacked the cardioprotective properties of other anticoagulants, while NSAIDS increased the risk of myocardial infarction.

However, he said, the MJA findings showed that the uptake of dabigatran had plateaued.

Professor Baker said the co-administration of NSAIDs with anticoagulant therapy was concerning.

“The risk of bleeding significantly increases if you’re on more than one antithrombotic agent, so stopping anti-inflammatories and/or aspirin if they’re not needed is probably a good thing if you’re starting a NOAC or warfarin.”

Professor Baker added that concerns about the non-reversibility with NOACs would soon be addressed with the US licensing antidotes for dabigatran, and an antidote for anti-factor Xa agents, rivaroxaban and apixaban may be just around the corner.

In October of 2015 the US Food and Drug Administration granted accelerated approval to idarucizumab for use in patients who had experienced a bleeding event while taking dabigatran. Studies are continuing into andexanet, a potential reversal agent for rivaroxaban and apixaban.

Professor Baker said around 15% of people died within 30 days of presenting with a thromboembolic event.

“It’s a sentinel event, so really it’s an area we need to devote more attention to,” he said, adding that the Australasian Society of Thrombosis and Haemostasis is conducting the Anticoagulation Reversal and Events Study to help to guide clinicians’ management decisions in patients experiencing a major bleed or stroke while on anti-coagulants.

The MJA findings come in the wake of a BMJ report this month that called into question the results of the ROCKET-AF trial. The BMJ reported that a defective point-of-care device was used to measure INR levels in the warfarin arm of the trial.


Poll

Do you prescribe novel oral anticoagulants regularly?
  • Yes, they're a better option than warfarin (40%, 20 Votes)
  • Maybe, if the patient is a good fit for them (32%, 16 Votes)
  • No, I'm not convinced they're better than warfarin (28%, 14 Votes)

Total Voters: 50

Loading ... Loading ...

5 thoughts on “Novel anticoagulants drive increase in overall use

  1. James Leyden says:

    Nearly everyone forgets the other side of the coin.   In the Adelaide Stroke incidence study  1/3 of strokes could have been prevented if people with AF were anticoagulated properly.   Aspirin does not prevent embolic stroke. IN the same study there were no over anticoagulation bleeds.  It has been estimated you need to have around 500 falls per year for the risk of trauma to outweigh the benefits of anticoagulation.  Every day on stroke units we see strokes that could have been prevented if AF was treated properly.  The fear of treatment is harmful. The community has been, and still is,  woefully under treated. Articles like this need to emphasize the reality of under treatment .

  2. Peter Bradley says:

    Absolutely right.. Hitherto, when all we had was warfarin, many patients who probably should have been anticoagulated, weren’t, mainly because of the inconvenience of regular blood tests, the dietary restrictions, and also the risks – which tended to sway in the direction of not treating quite often.

    These new druga appear to be the best answer to that, and one would predict the incidence of stroke to drop significanlty over time, as a result of more being treated.  So, over all – not really a bad thing.

  3. John Stokes says:

    As a doctor who needs an Anticoagulant I am more than happy with taking Warfarin. It has a long history of reliability, an excellent method of patient controlled drug dosage with a portable monitor, excellent reversibility with two reliable methods and easy monitoring of effect. None of these are matched by the new drugs. Who would prescribe oral hypoglycaemic  or insulin to diabetics without their patents being able to self measure the effect and adjust the dosage. The problems with warfarin are more related to our lazy attitudes to encouraging self monitoring and patient controlled anti coagulation than the efficacy of the other newer available medications. There has not been a reasonable study comparing well controlled patient controlled anticoagulant with the newer drugs. It needs to be done.

     

  4. John Stokes says:

    I am a specialist who needs an anticoagulant.

    Warfarin is my choice as it:

    Can be reversed by Prothrombinex, Vitamin K, and FFP,. the newer drugs can’t.

    I can monitor the effect easily myself at any time or any where with a simple portable device.

    i can adjust the dosage myself.

    i can confirm my level of anti coagulation. You can’t with the newer drugs. 

    Warfarin has a long history of safe usage.

    No trial has compared good patient modified control with the newer medications or shown their superiority.

    No drug companies are not making a fortune out of its introduction and usage.

    i will await a proper evaluation before changing.

     

     

     

  5. Dr Kevin B. Orr says:

    I have been on warfarin for 2 or more years (for AF, PAH and RHF). I have had no problems. I changed to an oral drug at one time but I had a feeling that I was lost, I did not know where my anticoagulaion was. I was much happier when I changed back to warfarin.KBO

Leave a Reply

Your email address will not be published.