Bivalrudin Trumps Heparin (Or Not)(Who Knows?)

10 out of 10 physicians employed by the Medicines Company approved this message.

Straight out of Jeff Drazen’s unbiased news pipeline, a treatment you might now start seeing more of in the Emergency Department: bivalrudin (Angiomax) for anticoagulation prior to PCI in the setting of STEMI.  In this trial, 2,231 patients across Europe were randomized pre-hospital (or at non-PCI hospitals) to either bivalrudin or heparin plus optional glycoprotein IIb/IIIa inhibitor.  The primary outcome, as typical of these sorts of trials, is another muddled composite: death from any cause, re-infarction (MI), or major bleeding not related to CABG.

Oh, wait, that was the original primary outcome.  In December of 2012, over three-quarters of the way through the enrollment period, the Medicines Company dropped re-infarction (MI) from the primary outcome.  It may or may not be a coincidence re-infarction due to stent thrombosis favored the control intervention, but I will leave that speculation up to the astute reader.  Regardless, the new final composite endpoint favored bivalrudin: 5.1% to 8.5%.  However, this outcome also depends on their own unique definition of “major bleeding”, which is different from TIMI and GUSTO.  If the TIMI and GUSTO definitions are used, the trend towards reduced bleeding with bivalrudin is still there, but the absolute differences become trivial and the overall primary outcome (original or eventual) is a wash.  Finally, this may all simply be a straw-man comparison for the safety outcome, as it’s reasonable to ask whether 69% of cases ought to be receiving prehospital glycoprotein IIb/IIIa inhibitor (an AHA Class IIb recommendation).

However, better questions may be – as are a recurring theme for the NEJM – do you trust the results of an open-label trial sponsored by the manufacturer, designed by the manufacturer, with data stored and dispensed to the academic oversight group by the manufacturer?  Are you less or more convinced when four authors are employed by the manufacturer, and the manufacturer employed a scientific communications firm for “editorial support”?  Why is NEJM publishing a trial that changed its primary outcome in clinicaltrials.gov – even, as the authors claim, to “reduce the necessary sample size”?

Physicians ought to be outraged at this transparent and unbalanced pharma shill – but, such occurrences have become so commonplace, it’s hard to not just surrender to lassitude.  Bivalrudin doubtless has an advantage in some specific subgroup, but with this sort of offal clogging the evidence, we’ll never really know.

“Bivalirudin Started during Emergency Transport for Primary PCI”
www.ncbi.nlm.nih.gov/pubmed/24171490