New Oral Anticoagulants Carry Risks and Benefits in Venous Thromboembolism

During the Southern Hospital Medicine Conference, held November 7-9, 2013, in New Orleans, LA, Steven Deitelzweig, MD, a hospitalist at Ochsner Medical Center, reviewed new oral anticoagulants (NOACs) used to treat venous thromboembolism (VTE).

In his “Venous Thromboembolism: New Evidence and Best Practice” presentation, Deitelzweig discussed the Pulmonary Embolism Severity Index (PESI), which estimates patients’ risk of mortality 30 days from pulmonary embolism (PE). While the original PESI assessed 11 patient characteristics — including age, history of cancer and heart failure, blood pressure, heart rate, and oxygen saturation — the simplified version of the PESI assesses 6 characteristics, Deitelzweig said.

Established NOACs include dabigatran, an oral direct thrombin inhibitor approved for VTE prophylaxis from atrial fibrillation (AF) in the United States; rivaroxaban, an oral direct factor Xa inhibitor; and apixaban, which acts similarly, but is not approved for VTE use. Studies have shown that all of those NOACs, as well as edoxaban, are non-inferior to warfarin for treating PE and deep vein thrombosis (DVT). According to Deitelzweig, major bleeding was non-inferior for edoxaban, 40% less for dabigatran, 46% less for rivaroxaban, and 69% for apixaban. As renal problems resulting from each drug were more likely if creatinine clearance was below 30 mL/min, Deitelzweig said patients should be screened and managed carefully for NOACs.

Deitelzweig recommended NOACs to be used if a patient is adherent and has poor INR control, TTR <60%, and good renal and hepatic function, though he said NOACs should be avoided if a patient is poorly adherent, has poor renal or hepatic function, is pregnant, has cancer, or is taking dual anti-platelet therapy, p-glycoprotein, or CYP3A4 inhibitors or inducers. Warfarin should still be used for VTE if a patient has cancer, Deitelzweig advised.

To manage acute gastrointestinal (GI) bleeding after NOAC use, healthcare providers should identify when the last NOAC dose was taken and administer oral charcoal if the dose was within 2 to 3 hours, Deitelzweig said. To perform dabigatran reversal, physicians should consider 25 to 50 units/kg IV of activated prothrombin complex concentrate or hemodialysis. After a first GI bleed, anticoagulation therapy may be reinitiated within 1week, Deitelzweig said.

Commenting on inferior vena cava (IVC) filters that trap blood clots, Deitelzweig said they are becoming increasingly popular, but are not recommended for primary prevention in patients with an increased risk of bleeding or contraindications for anticoagulation therapy. Deitelzweig warned that filter migration occurs in 2 to 6% of placements, and DVT and filter thrombosis can also occur.

The Society of Interventional Radiology states that absolute indications for all filters are documented evidence of PE or VTE, iliac, or femoropopliteal DVT, as well as contraindication to anticoagulation; failure or complications from anticoagulation; or recurrent PE despite adequate therapy.

The use of retrievable filters, which can be used as permanent filters, is indicated in PE and/or DVT; when there is a transient inability to anticoagulate; and for PE prophylaxis in high-risk patients. Retrievable IVCs are recommended for use in younger patients, since the durability, safety, and efficacy of those filters are unknown.

Deitelzweig said those filters should be retrieved in order to avoid the long-term complications associated with permanent filters, which include migration or fracture of filters, post-thrombotic syndrome, DVT, clot above the filter, and organ penetration. Retrieval rates range between 2 and 20%, and the major reason for those low rates is the fact that reporting is often lost in follow-up.

Discussing testing for hypercoagulability, Deitelzweig said the College of American Pathologists and the American College of Medical Genetics recommend testing patients who suffered their first VTE before the age of 50; have recurrent VTE; have VTE at any age, along with a strong family history; have VTE at an uncommon site; or have VTE related to the use of oral contraceptives, pregnancy, or immediate postpartum.

Deitelzweig recommended D-dimer, a protein fragment from fibrin degradation, as an “inexpensive, very useful test” to predict recurrent clotting problems after stopping anticoagulants for unprovoked VTE. A negative result can indicate a 3.5% annual risk for recurrent problems, while a positive result points to an 8.9% annual risk, Deitelzweig said.

Deitelzweig reminded the audience that “we need to talk to our patients” to find out their preferences and values in treatment, and then balance those findings against their risk of bleeding. Low-intensity warfarin should also be considered as an alternative, Deitelzweig said.