Warfarin and the New Oral Anticoagulants

San Antonio—For more than 50 years, warfarin was the only anticoagulant that patients could use. In the past 3 years, though, the FDA has approved 3 more oral anticoagulants: dabigatran etexilate, rivaroxaban, and apixaban.

Angela Allerman, PharmD, clinical pharmacy specialist at the Defense Health Agency Pharmacoeconomics Center, discussed the treatment options at the AMCP meeting during a session titled Clinical Efficacy and Cost Effectiveness of New Oral Anticoagulants.

While warfarin has a slow onset, has several food and drug interactions, and is inexpensive, the new oral anticoagulants have a fast onset, have no food interactions but some drug interactions, and are expensive. The drugs also have different indications. Warfarin, a vitamin K antagonist, is approved for stroke prevention in non-valvular atrial fibrillation (NVAF) and cardiac valve replacement and after hip surgery, knee surgery, venous thromboembolism, and myocardial infarction.

Dabigatran etexilate, a direct thrombin inhibitor, is approved in 75 mg and 150 mg capsules to prevent strokes in NVAF. Apixaban, a factor Xa inhibitor, is approved in 2.5 mg and 5 mg tablets to prevent strokes in NVAF. Rivaroxaban, a factor Xa inhibitor, is approved in 10 mg, 15 mg, and 20 mg tablets for stroke prevention in NVAF and after hip surgery, knee surgery, and venous thromboembolism.

According to Dr. Allerman, the quarterly costs of the drugs obtained from the Department of Veterans Affairs Federal Supply Schedule are similar: $468.15 for dabigatran etexilate, $500.03 for rivaroxaban, and $534.09 for apixaban. She noted that the prices in the private sector might differ. Dr. Allerman said there have been no head-to-head trials conducted to compare the new oral anticoagulants in preventing strokes in NVAF. However, indirect comparisons have found that the 3 new oral anticoagulants are superior to warfarin in treating atrial fibrillation (AF).

The American Stroke Association in 2012 released guidelines for AF that mentioned drugs should be chosen based on risk factors, cost, patient preference, drug interactions, and other clinical characteristics. Dr. Allerman also noted that healthcare professionals could assess risk factors for stroke in AF using the CHADS2 scoring system. Risk factors include congestive heart failure, hypertension, >75 years of age, diabetes, and stroke history.

When considering the use of warfarin to treat AF, Dr. Allerman said providers should be aware that 25% of patients discontinue using the drug during the first year, 50% of patients are considered ineligible to take the drug, and 40% of patients who are candidates for the drug do not receive treatment. She added that a study of 13,000 people found that the risk of stroke was 1.3% in patients treated with warfarin for NVAF and 2.1% in patients who did not receive an anticoagulant. In addition, clinical trials have shown that 2% to 5% of patients taking warfarin for AF have major bleeding each year while up to 7% of patients in real world settings have major bleeding when they receive warfarin.

Dr. Allerman suggested payers must consider several factors when deciding what drugs to cover. She suggested they conduct or examine a cost-effectiveness analysis of the options and research what medications are in the pipeline. She added that healthcare professionals should consider patient preferences, assess compliance to the medications, monitor adverse events, and follow-up with patients on a regular basis.