By Elaine Schattner, MD|December 7th, 2010
On the hematology front –
Last weekend at the annual meeting of the American Society of Hematology (ASH), researchers presented data on a new kind of blood thinner. Rivaroxaban (Xarelto) is a pill that works by blocking the activated form of human clotting factor X (Xa). The NEJM published the EINSTEIN* findings on-line ahead of print, coincident with the presentation.
The research includes two reported trials. In the first, an open-label randomized study of 3449 patients with acute deep venous thrombosis (DVT), subjects received either rivaroxaban pills or a standard treatment regimen starting with an injected blood thinner (enoxaparin) followed by an oral Vitamin K antagonist, like coumadin. The main findings in this Acute DVT Study was that the new drug, rivaroxaban, is as good (“non-inferior”) in terms of preventing recurrent clot as is the older regimen and bears a similar safety profile.
The second, parallel EINSTEIN-extension trial involved randomization of 1197 patients after treatment for acute DVT to take oral rivaroxaban or a placebo for an additional 6-12 month period. In this study, patients taking the experimental anticoagulant had fewer blood clots than those on placebo. Unsurprisingly, there was a slightly increased reported incidence of major bleeding (4 patients, 0.7%) in patients on the blood thinner relative to placebo (0 patients, 0%). This difference was not statistically significant.
Both trials were funded by Bayer Schering Parma and Ortho-McNeil. According to a Bayer press release of last August: “If approved by the FDA, Ortho-McNeil, a division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. (a Johnson & Johnson Company), will commercialize rivaroxaban in the U.S.”
What’s good, clearly, is that several effective anticoagulants are emerging as alternatives to heparin, which must be injected, and coumadin. In October the FDA approved the first of these drugs, dabigatran (Pradaxa), for prevention of stroke in patients with atrial fibrillation. This was big news in cardiology circles, with reason. Another area of use for these agents would be in prophylaxis for DVT in patients who undergo hip replacement and some other kinds of major surgery.
In my experience as a hematologist, and as a patient who’s had a DVT, I know that coumadin dosing is not straightforward. Because the therapeutic dose varies so much among individuals in ways that depend on genetic factors and potentially change over time with diet, patients need provide initially frequent and then periodic blood samples. The repeated blood tests don’t require large amounts of blood, but they’re annoying and costly. What’s more, the hassle – pain of blood draws, driving or walking to a clinic for sample taking, waiting for results – interferes with quality of life.
Giving intravenous blood thinners is not convenient either, as these need carefully-monitored infusion of the drug, and it’s easy to overshoot or undershoot the dose. Injectable blood thinners like low molecular weight heparin are easier to dose than conventional heparin, but still it’s pretty unpleasant for a patient to have to inject herself once or twice a day with a needle.
Soon we’ll see what the FDA says about rivaroxaban. I’m not excited about this one agent as opposed to any other, but I am enthusiastic about this new class of drugs. These should benefit people whose medical conditions warrant the use of blood thinners.
*The “EINSTEIN” investigators are based in the Netherlands and are listed in the original paper. It’s hard to find an explanation of the acronym.