COMMENTARY

Anticoagulation in Patients with Cancer and VTE

Samuel Z. Goldhaber, MD

Disclosures

July 16, 2015

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Treating Cancer Patients with VTE

Samuel Z Goldhaber, MD: This is Dr Sam Goldhaber from the Clot Blog at theheart.org on Medscape recording from the American College of Cardiology Scientific Sessions in San Diego. Today, we are going to talk about the important topic of cancer patients who suffer acute [deep venous thromboembolism] DVT or acute pulmonary embolism and what strategies should be used to anticoagulate them.

What we've been doing traditionally is administering low-molecular-weight heparin as monotherapy, rather than low-molecular-weight heparin as a bridge to warfarin. The reason we do this is a pivotal trial of cancer patients with VTE that was published by Agnes Lee in the New England Journal of Medicine[1] about 12 or 13 years ago. In that trial she randomized cancer patients with VTE either to dalteparin as monotherapy without any oral anticoagulant or to dalteparin as a bridge to warfarin. It turns out that the dalteparin monotherapy patients had half the recurrence rate of the patients who were switched over from dalteparin to warfarin, even though the warfarin group in her trial had therapeutic INRs, with a target INR between 2.0 and 3.0. As a result, all three of the major cancer guideline writing committees have recommended that low-molecular-weight heparin should be administered as monotherapy to these patients. Furthermore, unless the cancer is cured, anticoagulation should be continued indefinitely.

Enter the NOACs

Along come the novel oral anticoagulants—the NOACs. Patients in the pivotal trials[2,3,4,5,6] of acute DVT and pulmonary embolism who were randomized to a NOAC vs conventional warfarin therapy could be brought into the trial even if they had cancer. It turns out that in the 27,000 or so patients who were admitted into these pivotal NOAC VTE trials, almost 1000 had cancer.[7] Now, these 1000 or so patients were in general not as sick as the patients in the Agnes Lee study published 12 or 13 years ago. Their cancers tended to be a little bit more remote. The patients tended not to be on active chemotherapy and they were allowed into the trial. We now have an opportunity to compare how these cancer patients with VTE fared on NOACs vs warfarin. In terms of efficacy prevention of recurrent VTE, there was a strong trend in favor of NOACs over warfarin for prevention of recurrent disease. This trend did not reach statistical significance.

The other problem we always fear with cancer patients is an increased risk of major bleeding. The major bleeding rates were compared for NOACs vs warfarin in these cancer patients with VTE. Again, there was a trend toward less major bleeding with the NOACs than with warfarin. But again, the difference did not achieve statistical significance.

Putting this all together, the NOACs appear—at first glance—to be a reasonable choice for cancer patients with VTE, especially the healthier cancer patients.

The Hokusai VTE Cancer Study

What we're lacking though is a trial that is specifically dedicated to studying cancer patients with VTE. Just about to start is the Hokusai-VTE Cancer trial that is going to compare dalteparin as monotherapy (which was used by Dr Agnes Lee) vs edoxaban. This trial will continue to treat patients for about a year. Efficacy will be judged on preventing recurrent VTE, and safety will be judged on preventing major bleeding, and both will be compared between the two groups. This will be an important prospective randomized trial.

For the moment, low-molecular-weight heparin as monotherapy remains the guideline-recommended course of action to take for cancer patients with VTE. But if you care for a lot of cancer patients who have pulmonary embolism or DVT, as I do, you'll find that many of them after a while are just sick and tired of daily injections—they get to a point where they don't want to take daily injections any longer. Certainly, if that is the case, it looks from the data that we've collected and meta-analyzed that NOACs are a very reasonable second choice to low-molecular-weight heparin as monotherapy. Who knows—if this Hokusai VTE Cancer study favors edoxaban over dalteparin, perhaps edoxaban will become the new standard of treatment for these patients.

This is Dr Sam Goldhaber, signing off for the Clot Blog.

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