Blog | Friday, May 18, 2012

Can someone tell me why I should care about EINSTEIN-PE?


EINSTEIN-PE was published in the April 5 edition of the New England Journal of Medicine, the place to find cutting edge, non-inferiority, open-label trials, written and sponsored mostly or fully by pharmaceutical companies.

What I learned from reading this article is that rivaroxaban is a great generic drug name, as I'm not sure what syl-LABUL to put the em-PHASIS on: RIVA-ro-xaban or is it riva-ROXA-ban? It really doesn't matter, but it's one reason that I'm not rushing out to find converts to its cause.

In this day in age of evidence-based medicine I'm not sure why we as internists should have to put up with an open-label non-inferiority trials to guide our prescribing habits. They might as well have glued $20 bills or coupons to a local Sushi restaurant in the journal. I've heard that there is a worldwide shortage of placebo, rising cost of sugar because of the cost of gas. It must be at the heart of this.

It turns out that rivaroxaban is not worse than enoxaparin and warfarin, which many of us are very familiar with and our clinics can easily manage. For example, look at the study's Kaplan-Meier curves minus the grossly magnified inserts that they published. Based on these curves I can safely say that I see no clinically meaningful endpoint to suggest that I should jump ship quite yet.

For the sake of argument, let's do the math. For the primary outcome of recurrent nonfatal venous thromboembolism the absolute rate reduction of rivaroxaban vs. enoxaparin/warfarin was 0.3 percentage points (based on the absolute event rate, not the hazard ratio.) The number needed to treat is 333. It appears that there is a 1.1 percentage point difference in first major or clinically relevant nonmajor bleeding episode the winner here, rivaroxaban. Number needed to prevent said bleeding episode of 91.

Maybe I'm just against these oral direct thrombin inhibitors and factor Xa inhibitors because they take all of the fun out of warfarin management.

I'll continue to prescribe rat poison. I'm good at it, it's cheap, and it works.

Addendum: Finally, in addition to actually monitoring all 4,900 patients for 6 months of therapy they just stopped when they felt (had proven statistical utility ... er, power) that enough patients had recurrent events. So we really don't know what truly happens when you put people almost 5,000 people on this med over the course of 6 months.

Justin Penn, MD, ACP Associate Member, attended medical school at the University of Washington School of Medicine and trained in internal medicine at the University of Rochester, where he is serving as Chief Resident. This post originally appeared at his blog, Musings of an Internist.