Los Angeles, CA—Several new drugs have recently entered the market as effective alternatives to warfarin for the treatment of patients with nonvalvular atrial fibrillation (NVAF).
RE-LY: Dabigatran Effective for Patients with NVAF
Relative to warfarin, the direct thrombin inhibitor dabigatran etexilate (Pradaxa) is effective in preventing stroke and other adverse vascular outcomes in patients with diabetes and NVAF, as well as in nondiabetic patients with NVAF, based on results of a subanalysis of the Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) trial.
The safety of dabigatran was also similar among those with and without diabetes in the RE-LY trial, said Harald Darius, MD, PhD, Director of the Department of Medicine, Vivantes Neukölln Medical Center, Berlin, Germany, at the 2012 American Heart Association meeting.
Patients with NVAF who have diabetes have up to double the risk for a stroke compared with nondiabetic patients.
RE-LY was a global, phase 3 clinical trial of 18,113 patients, investigating whether dabigatran was as effective as open-label warfarin that was titrated to a dose to achieve a target international normalized ratio (INR) of 2.0 to 3.0 for stroke prevention. The trial enrolled patients with NVAF and at least 1 other known risk factor for stroke. Patients were followed for a minimum of 1 year.
Of the 18,113 patients, 4221 (23%) had diabetes on enrollment. This subanalysis compared the efficacy of dabigatran 150 mg twice daily or 110 mg twice daily versus warfarin in patients with and without diabetes in the NVAF population (the 110-mg twice- daily dose is not approved by the US Food and Drug Administration [FDA]).
Patients with diabetes had a higher prevalence of vascular disease than those without diabetes, including hypertension, coronary artery disease, and peripheral vascular disease.
In the diabetic patients who were randomized to warfarin, INR was not as well controlled as in those without diabetes: the median time in the therapeutic range was 65% for patients with diabetes versus 68% for nondiabetics. Nevertheless, among patients with NVAF, those with and without diabetes derived similar relative benefits from dabigatran 150 mg or 110 mg compared with warfarin, reported Dr Darius.
The risk reduction of stroke and systemic embolism with dabigatran 150 mg twice daily relative to warfarin was 34% in patients without diabetes and 38% in those with diabetes. The rates of ischemic stroke, vascular death, and death were all similarly reduced in the dabigatran arm relative to the warfarin arm in patients with and without diabetes.
Compared with nondiabetics, patients with diabetes had a 44% higher risk of major bleeding (P <.001), but only a nonsignificant lower increase in intracranial bleeding risk; no significant differences were seen in bleeding events between dabigatran and warfarin.
ROCKET AF Study: Rivaroxaban Also Effective in Patients with Diabetes and NVAF
In the ROCKET AF trial, the relative efficacy and safety of rivaroxaban (Xarelto) was similar to warfarin in patients with and without diabetes, supporting its use as an alternative to warfarin for stroke prevention in patients with diabetes and NVAF, said Jonathan L. Halperin, MD, Robert and Harriet Heilbrunn Professor of Medicine at Mount Sinai School of Medicine, Director of Clinical Cardiology Services at the Zena and Michael A. Wiener Cardiovascular Institute at the Mount Sinai Medical Center, New York City.
More than 14,000 patients with NVAF were enrolled in ROCKET AF, of whom 5635 had diabetes. In patients with diabetes, the rates of primary events with rivaroxaban versus warfarin were 1.59 versus 2.15 per 100 patient-years, respectively; these were similar to the rates in patients without diabetes. The same was true for the rates of ischemic stroke and systemic embolism.
The rates of any major or nonmajor clinically relevant bleeding in patients with diabetes who received rivaroxaban were similar to those receiving warfarin, with a trend toward less frequent intracranial hemorrhage with rivaroxaban.
Apixaban Newest Therapy for NVAF
At the 2012 European Society of Cardiology meeting, researchers presented a secondary analysis of data from the clinical trial ARISTOTLE, which showed that the oral factor Xa inhibitor apixaban (Eliquis) reduced the risk of stroke and systemic embolism by 21%, the risk of mortality by 11%, and the risk for bleeding by 31% relative to warfarin in patients with NVAF. The secondary analysis also looked at renal impairment in the patient population, showing that patients with the greatest renal impairment had the most benefit with apixaban relative to warfarin, because of the higher risk of bleeding associated with the latter drug.
On December 28, 2012, the FDA approved apixaban for the risk reduction of stroke and systemic embolism in patients with NVAF based on the safety and efficacy data from ARISTOTLE that showed fewer stroke events and reduced bleeding in patients taking apixaban compared with warfarin.
Apixaban was not studied in patients with prosthetic heart valves or in patients with atrial fibrillation that is associated with a heart valve problem. These patients should therefore not use this medication. As with other FDA-approved anticoagulants, bleeding is the most serious risk with apixaban, although the incidence is lower than with warfarin.