BETHESDA, MD 11 Feb 2016—A revised guideline from the American College of Chest Physicians favors the use of dabigatran, rivaroxaban, apixaban, or edoxaban over traditional vitamin K antagonist (VKA) or low-molecular-weight heparin (LMWH) therapy for the long-term treatment of venous thromboembolism (VTE) in patients without cancer.
"Antithrombotic Therapy for VTE Disease," released online in December by the publishers of Chest, is the 10th published version of the guideline, which updates a guideline released in early 2012. In that version of the guideline, VKA or LMWH therapy was preferred over the two available "new oral anticoagulant drugs" for the long-term treatment of pulmonary embolism or deep vein thrombosis.
Non–vitamin K oral anticoagulants. Oral anticoagulants that do not antagonize vitamin K have been on the U.S. market since 2010, when dabigatran was approved.
The 2012 guideline used the term new oral anticoagulant drugs to refer in general to direct inhibitors of thrombin or factor Xa. The 2015 guideline uses the term non-vitamin K oral antagonist yet retains the popular abbreviation NOAC.
NOACs have simpler dosing regimens than VKAs and, unlike VKAs, do not require healthcare providers to monitor patients' International Normalized Ratio (INR).
A potential downside to the use of NOACs—the lack of reversal agents—became less critical last fall after FDA approved the licensing of a monoclonal antibody product that counteracts the anticoagulant effects of dabigatran. Other NOAC reversal agents are in development.
James Lee, clinical pharmacist in ambulatory pharmacy services at the University of Illinois Hospital and Health Sciences System in Chicago, said the availability of reversal agents for the NOACs will ease concerns among clinicians about bleeding episodes in patients treated with these medications.
"It makes me feel a lot better," Lee added.
"I think it's important that reversal agents are available," said Daniel Witt, vice chair and clinical professor at the University of Utah College of Pharmacy in Salt Lake City. "But when you look at the actual outcomes of bleeding . . . associated with the new drugs, compared to warfarin, even without the availability of reversal agents most patients that suffer bleeding complications tend to do as well as, if not better than, patients treated with warfarin."
According to the guideline, research indicates that despite the lack of specific reversal agents for NOACs, the risk of a fatal bleed in patients treated with these anticoagulants "appears to be no higher" than for patients taking VKA therapy.
Witt is a past expert panelist for the VTE guideline writing group but was not involved in the most recent revision of the document. He said the recommendation in favor of NOACs was probably the most notable revision in the guideline.
"For the treatment of venous thromboembolism, . . . I think it makes a lot of sense to use the newer drugs over low-molecular-weight heparin and warfarin therapy. The outcomes are not dramatically different," Witt said. "But I think that the big thing is that [the newer drugs] are so much easier to coordinate than low-molecular-weight heparin and warfarin."
Witt said that long-term treatment of VTE usually requires patients to self-administer their medications and travel to a clinic or laboratory for regular INR monitoring and subsequent dosage adjustments.
"With the new drugs, you just prescribe the medication to be taken orally, and you don't have to go through all that," Witt said.
But the guidelines emphasize that NOACs are contraindicated in some patients, such as people with liver disease that affects the accuracy of INR test results. In these patients, the guideline recommends LMWH as the preferred VTE treatment. For patients with severe kidney impairment, NOACs and LMWH are contraindicated, and VKA therapy is the recommended strategy for VTE treatment.
"There are very clear things that you need to think about before determining whether or not your patient is appropriate for the new agents," Lee said.
Patients. Lee said patient factors, including the cost of treatment and a preference for once-daily therapy, should also influence the choice of an anticoagulant regimen.
Patient factors are likewise considered in the guideline, which states that therapy may change "in response to the patient's circumstances or preferences during long-term or extended phases of treatment."
"If you do have a choice, great. Use something that works for the clinician and the patient. But in some cases, the patient might not have all those options in front of them," Lee said.
Patient preference is evident in a section in the guideline that discusses the role of aspirin in VTE prevention.
According to the guideline, aspirin is not "a reasonable alternative to anticoagulant therapy in patients who want extended therapy," but it may help prevent recurrent VTE in patients who would otherwise refuse anticoagulant therapy.
Lee said he was pleasantly surprised by this recommendation and said it serves to "meet the risk halfway" in patients who are not receptive to anticoagulant therapy.
"No one would really say [to use] aspirin for somebody that really should be on an anticoagulant," Lee said. But he said the guideline's discussion of aspirin acknowledges that the antiplatelet agent is better than using nothing at all to prevent recurrent VTE.
Pharmacy's place. Both Witt and Lee said they expect traditional pharmacist-managed anticoagulation programs to retain an important place in patient care, even as NOACs become more widely accepted.
"Warfarin is a less expensive therapy in terms of the cost of the drug to the patient. So I think that there still is a place for warfarin therapy management," Witt said. He added that because the newer oral anticoagulants are "very dependent on renal function" for elimination, there will continue to be a need for warfarin as a treatment option.
Lee said his health system has "a very sizeable population of patients where warfarin works very, very well."
"I don't think that it's going to disappear" anytime soon, Lee said.
He said pharmacists in his health system work with patients who take NOACs to ensure that the therapy is safe and appropriate.
Witt said that even though patients taking a NOAC don't need the regular bloodwork that is necessary for managing VKA therapy, it's still necessary to "keep an eye on the patients" to minimize their bleeding risk.
"Situations are going to arise where they might have to have an invasive procedure, or there needs to be some management and coordination of their therapies," Witt said. "And patients still need to be educated about the signs and symptoms of bleeding that they need to be on the lookout for."