Rivaroxaban Equals LMWH for Treatment of PE

Updates on anticoagulation therapy and oral contraceptives, intracranial hemorrhage, and pulmonary embolisms are presented.

In the EINSTEIN PE study³ of 4832 patients with acute symptomatic pulmonary embolism (PE) with or without deep vein thrombosis, it was demonstrated that rivaroxaban (Xarelto, Bayer) is at least as effective as the standard therapy of subcutaneous injections of the low molecular weight heparin (LMWH) enoxaparin and warfarin.

In this study, a total of 2419 patients received rivaroxaban 15 mg by mouth twice daily for 3 weeks, followed by 20 mg once daily. Patients receiving oral rivaroxaban had a 50% lower rate of major bleeding (ie, intracranial hemorrhage and retroperitoneal bleeds [hazard ratio 1.12, P = .003]) and the risk of recurrence was the same for both groups. Study researchers said the “efficacy and safety results were consistent irrespective of age, body weight, gender, renal function and cancer, and there was no evidence for liver toxicity with rivaroxaban.”

PE is a disorder that occurs in all ages and can be fatal if not treated immediately and aggressively. In some instances, PE patients may be treated as outpatients and receive LMWH for 5 to 10 days along with long-term warfarin. US patients are often hospitalized for up to 7 days and receive LMWH and warfarin treatment.

Currently, rivaroxaban is not approved for use in the United States for acute PE, but if it were, it could decrease the amount of time patients spend in the hospital. It could potentially decrease the overall cost of drug treatment as well, because monitoring warfarin therapy would not be necessary.

Dabigatran⁴ or Rivaroxaban,⁵ Which Do I Choose?

• Patient compliance may be better with rivaroxaban because it is dosed once daily.
• Dabigatran should be avoided in patients with severe renal failure.
• Renal function is less of a problem with rivaroxaban, but should be considered.
• Dabigatran can be dialyzed, rivaroxaban cannot.
• Higher doses of dabigatran in the elderly may be problematic.
• Only the low dose of dabigatran should be used with P-glycoprotein inhibitor verapamil, and cautious use with close monitoring is recommended, especially in patients with renal impairment taking quinidine and amiodarone.
• Dabigratran should be avoided with dronedarone.
• Overdosing with either drug can be problematic since neither has a readily available antidote.

Mr. Brown is professor emeritus of clinical pharmacy and a clinical pharmacist at Purdue University College of Pharmacy, Nursing, and Health Sciences, Department of Pharmacy Practice, in West Lafayette, Indiana. This column’s information is based on current studies and references, but it may be changed without notice with newer studies or with different patient populations.

References:

1. Food and Drug Administration website. FDA drug safety communication: Updated information about the risk of blood clots in women taking birth control pills containing drospirenone. April 10, 2012. www.fda.gov/Drugs/DrugSafety/ucm299305. Accessed May 1, 2012.

2. Hart RG, Diener HC, Yang S, et al. Intracranial hemorrhage in atrial fibrillation patients during anticoagulation with warfarin or dabigatran: The RE-LY trial. Stroke 2012: DOI:10.1161/?STROKEAHA.112.650614.3.

3. Turpie AG, Jamal W, Schmidt A, et al. XAMOS: A non-interventional study comparing oral rivaroxaban with conventional regimens for thromboprophylaxis after major orthopaedic surgery of the hip and knee. British Society of Hematology 2012 Scientific Meeting; April 16-18, 2012; Glasgow, Scotland

4. The EINSTEIN-PE investigators. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med. 2012; 366:1287-1297.

5. Pradaxa (dabigatran etexilate) package insert. Boehringer Ingleheim, Inc. 2010.

6. Rivoraxaban (Xarelto) package insert. Bayer