VTE update covers new drugs, recommendations

Alternatives to warfarin will be available soon.

Currently, it is the patient who feels pain if prophylaxis against venous thromboembolism (VTE) is not successfully implemented. Soon, however, hospitals also may suffer when a clot occurs, predicted Geno J. Merli, FACP, during an Internal Medicine 2010 session on deep vein thrombosis (DVT) and pulmonary embolism (PE).

“Don't be surprised if we see VTE pop up” as a readmission diagnosis under scrutiny, said Dr. Merli, a professor of medicine and chief medical officer at Thomas Jefferson University Hospital in Philadelphia.

VTE prophylaxis has already made The Joint Commission's list of Patient Safety Goals, which call for anticoagulation to be managed by protocol. “Using unfractionated heparin and even low-molecular-weight heparin, we're going to have to have a guideline to manage those patients,” said Dr. Merli.

Either type of heparin is acceptable under the Joint Commission goals, he noted, and his hospital still regularly uses the unfractionated type, dosed by the weight-based method. “This does mean that our housestaff does have to check the aPTT [activated partial thromboplastin time] on a regular basis in the first 24 hours to adjust the dosing,” Dr. Merli said.

He also discussed some other issues in monitoring and dosing of heparin. Prior guidelines from the American College of Chest Physicians advised continuing unfractionated heparin until the patient's INR is greater than 2 for two consecutive days, but that time frame's been reduced to 24 hours in current guidelines. “Most of us want to get the patient out of the hospital, so we're not keeping them two consecutive days,” said Dr. Merli.

Heparin dosing has attracted news and FDA warnings recently because of a 10% decline in potency in the new formulation. This reduction in potency requires no changes if a patient is being injected subcutaneously. It does, however, merit closer monitoring—and possibly greater doses—for patients taking it intravenously, although there are no specific recommendations for increased doses. “You have to maybe be dosing the patient more aggressively if you're using an IV,” Dr. Merli said.

A little more aggression may also be appropriate in the length of time that prophylaxis is continued, especially in cancer patients. Dr. Merli predicted that cancer surgeries would soon be a major focus of anti-VTE efforts. “I think we're going to see new recommendations in the [American College of Chest Physicians] guidelines that will be coming,” he said.

Several studies, including last year's Million Women Study, have shown that patients who have surgery for abdominal and pelvic cancers face a clot risk for at least a month. In the [EACHAT]RISTOS trial, 40% of surgical cancer patients' VTEs occurred after discharge, and the risk factors were the same, whether the clot appeared early or late.

This means that physicians need to assess cancer patients' risk at discharge, using factors like whether the patient is mobile—and, if appropriate, make sure that prophylaxis is continued through the transition to outpatient care, perhaps for as long as 30 days. “We know the incidence goes out for orthopedics, but the cancer group—we have to think about this population,” said Dr. Merli.

He also offered some thoughts on dealing with cancer patients who have been diagnosed with a clot. “I hope you've all switched to using low-molecular-weight heparin for treating the cancer patient with thrombosis. I think it is the better way to go,” he said. The heparin is recommended for three to six months, but then guidelines call for continuing either it or warfarin indefinitely, or until the cancer is resolved.

“No one is going to pay for it indefinitely, and the patient may not want to take injections indefinitely,” said Dr. Merli. Patients' concerns and the other treatments they are receiving are significant factors to consider, he advised. “Warfarin's a terrible drug to manage during chemotherapy.”

Soon clinicians will have some alternatives to warfarin to consider: dabigatran, apixaban and rivaroxaban. “These are hot drugs. They are going to be out there very soon,” said Dr. Merli.

The drugs, which are awaiting FDA approval, have the potential to prevent clots as effectively as warfarin, with possibly reduced risk of bleeding and no need for monitoring, but Dr. Merli warned of their shortcomings. “When these drugs came out, they said, ‘Don't worry. There are no drug/drug interactions. There are no food interactions. You don't have to monitor them. It's the panacea of all drugs.’ But as you look at these drugs, they will have interactions.”

In addition to the risk of interactions with other drugs, it's also not clear how the new agents will work out in patients with renal impairment or liver disease, none of whom were included in trials. “Keep that in mind,” said Dr. Merli. “These are the kind of people we take care of.”

Overall, though, Dr. Merli was hopeful about the potential of the new drugs. “I think they'll be effective agents,” he said. There's also a new kind of warfarin in the pipeline, he noted. “You'll see it probably within the next year. You monitor it the same way, but it has great predictability for management, so those of you who run anticoagulation clinics, you might still be in business,” he said.

Whichever anticoagulant a physician chooses, eventually a decision will have to be made about whether to discontinue it. For that, Dr. Merli likes the D-dimer test, although it poses dilemmas of its own. “The question is what do I do when I get it back? A normal is 0.5. What do I do when it comes back 0.6?” he asked. “You're going to have to decide what D-dimer is going to be a decision point for you.”

Ultrasounds are an alternative method that some physicians use for deciding when therapy is no longer needed, but Dr. Merli doesn't think the evidence is there yet. “D-dimer is still a better way to look at things,” he said.

And then there's always the option of just playing it safe. “I treat patients indefinitely who have an idiopathic clot,” Dr. Merli said. “I know people disagree.”