Wednesday, December 12, 2012

Next Up – Apixaban!

The latest installment of propaganda in the NEJM comes from Pfizer and Bristol-Meyers Squibb, the joint venture behind apixaban.  Along with rivaroxaban, apixaban is an oral Factor Xa inhibitor, another option in the procession of potential warfarin replacements.  The Xa inhibitors, while they've had their problems, improve upon their main competitor – dabigatran – because they can be reversed in the emergency setting using prothrombin concentrate complexes (PCCs).  Dabigatran, as we all know, has no practical reversal strategy.

This is AMPLIFY-EXT, the extended treatment option from AMPLIFY – where apixaban is continued for an additional 12 months for prophylaxis against recurrent venous thromboembolism.  In isolation, looks great!  The placebo group had an 8.8% VTE recurrence in the study period vs. 1.7% in either of the two apixaban doses.  And, major bleeding in the placebo group exceeded the apixaban groups – 0.5% vs. 0.2% and 0.1%.  More effective and safer than a sugar pill!

So, what's the problem?  Well, this is the third apixaban trial to be published in the NEJM in the last two years.  The first one, apixaban for acute coronary syndrome, showed no benefit and increased bleeding.  The next, apixaban for stroke prevention in non-valvular atrial fibrillation (ARISTOTLE), showed non-inferiority to warfarin – but the rate of major bleeding in that study was 2.1% per year.  Then, the NEJM also has a recent article regarding aspirin for the prevention of recurrent VTE – where the placebo group only had a VTE recurrence risk of 6.5% rather than the 8.8% observed in AMPLIFY-EXT.

You can't directly compare trial populations, of course, but it doesn't make any sense that bleeding would be reduced compared to placebo.  And, it's a straw man comparison with placebo – the correct comparison is rather head-to-head against a potentially efficacious agent, such as low-dose aspirin.  After all, low-dose ASA is pennies a day, rather than the ~$10 per day for apixaban.

Can't blame the pharmaceutical companies for selling, can only blame the suckers for buying.

"Apixaban for Extended Treatment of Venous Thromboembolism"

1 comment:

  1. Hi Ryan. Nice comments on the Apixaban paper. More papers coming out in the BMJ and Annals of Internal Medicine this month on a similar theme. Seems to me as though there are still some fairly fundamental questions to ask about these agents.

    As EPs we will no doubt be meeting more of them soon though!

    St.Emlyn's blog post here if you are interested :-)



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