Novel Oral Anticoagulants Enter the Arena Bringing Alternatives to Warfarin

Novel alternatives to warfarin are being developed at a fast pace, and clinical data suggest that these drugs are associated with a lower risk for bleeding episodes compared with warfarin. Healthcare providers and payers are attempting to determine which agent has the best efficacy and safety profile and whether the new oral options truly present advantages over the longtime standard, warfarin, according to Jeffrey Weitz, MD, FACP, professor of medicine, McMaster University, Ontario, Canada. Dr Weitz presented an overview of the novel oral coagulants to attendees at the Plenary Session titled “Novel Oral Anticoagulants: Clinical Conundra.”

These novel oral anticoagulants (NOACs) are associated with less bleeding risk compared with warfarin, and may offer improvements in efficacy. Warfarin, a vitamin K agonist, is effective in reducing the risk of stroke and mortality in patients with nonvalvular atrial fibrillation, but increases the risk of bleeding. Warfarin also requires variable dosing and regular monitoring in order to stay within a narrow therapeutic range. The NOACs act through inhibition of key coagulation factors such as factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran).

To date, the available trial data for NOACs do not address whether these new agents will lead to improved outcomes, or whether they are cost-effective compared with warfarin. “We are fortunate that we have alternatives to warfarin, but we are still learning how to use the anticoagulants at the right time and [in the] right patient,” Dr Weitz said. The wrong patient for these new agents would be a patient who is stable on warfarin, has a creatinine clearance less than 30 mL/min, has severe hepatic dysfunction, or is noncompliant with warfarin, according to Dr Weitz.

Dr Weitz asked, “So how do we choose among the anticoagulants?” To illustrate some of the key differences between the new agents, Dr Weitz described various characteristics of dabigatran, rivaroxaban, apixaban, and edoxaban, while cautioning that in the absence of head-to-head studies, comparisons are difficult to make. Each drug has a different half-life, for example, and thus may have unique clinical utility. There is variability with regard to drug-drug interactions that could be important for some patients. Drugs that may potentially interact with NOACs include verapamil, diltiazem, amiodarone, dronedarone, and azole antifungals.

Two of the new agents—rivaroxaban and apixaban—are less affected by renal impairment and are also associated with a lower risk for dyspepsia or upper gastrointestinal complaints, noted Dr Weitz. Dabigatran is associated with a lower risk of ischemic stroke, he said. Rivaroxaban dosing is once daily while the dosing for the other 3 agents is twice daily.

Additional clinical trial data will help provide a clearer picture with regard to these novel options. The results from ENGAGE TIMI-AF, a noninferiority trial of low- and high-dose edoxaban versus warfarin, are being released during this year’s Scientific Sessions.

The evidence so far show that the “new oral anticoagulants are more convenient and at least as effective as warfarin but produce less intracranial bleeding,” Dr Weitz said. “Careful selection of patients and appropriate agent are important for optimal use of new oral anticoagulants.”