Bristol-Myers Squibb Company and Pfizer Inc. have reported results of a post-hoc sub-analysis from the phase III ARISTOTLE trial. Patients with non-valvular atrial fibrillation (NVAF) who are anti-coagulated to reduce the risk of stroke often undergo procedures for which temporary discontinuation of the anticoagulant prior to and following the procedure is sometimes warranted.

This sub-analysis describes the overall rates of key post-procedural outcomes, such as stroke or systemic embolism and major bleeding, among Eliquis and warfarin patients who underwent a procedure during the ARISTOTLE trial, and examined any differences in post-procedural events according to whether or not study drug was interrupted. This sub-analysis was presented today at the ESC Congress 2013, organized by the European Society of Cardiology, in Amsterdam.

The results showed that in the 30-day period following a procedure, rates of clinical events (stroke or systemic embolism, major bleeding, and all-cause death) were comparable in the Eliquis and warfarin treatment arms.

Among patients treated with Eliquis, event rates in the 30-day period following a procedure were similar whether Eliquis was stopped prior to the procedure or continued during the procedure. In patients taking warfarin, there was at least a twofold higher rate of major bleeding and death during the 30-day period following a procedure when warfarin was continued during the procedure compared to when warfarin was stopped prior to the procedure.

“For patients with NVAF who undergo procedures, the rate of anticoagulation-related adverse events appears to be similar whether the patient is chronically anticoagulated with apixaban or warfarin,” said study lead investigator Dr Renato Lopes of Duke University Medical Centre in Durham, North Carolina. “For NVAF patients for whom interruption of anticoagulation for a procedure is required, these findings suggest that using apixaban instead of warfarin, which is more challenging to stop and restart, may simplify the management of peri-operative anticoagulation in NVAF patients.”

There were 11,417 procedures in 6,162 patients from the 18,201 patients enrolled in the ARISTOTLE trial. The most common procedures were dental extraction/oral surgery, colonoscopy, upper endoscopy, and ophthalmic surgery. For 4,082 (35.8 per cent) procedures, study drug was not stopped. In the 7,335 procedures (64.2 per cent) where study drug was stopped, the median time of study drug stop was four days before the procedure for both Eliquis and warfarin-treated patients. The procedures were classified as major if they required general anesthesia, and procedures were also classified as emergent or non-emergent by investigators.

Among patients undergoing procedures in the ARISTOTLE trial, stroke and systemic embolism were uncommon and the 30-day post-procedure rates for these events were not statistically different in the two treatment arms (0.33 per cent for Eliquisvs. 0.53 per cent for warfarin). Major bleeding occurred in a comparable number of patients 30 days post-procedure in the two treatment arms (1.57 per cent for Eliquisvs. 1.81 per cent for warfarin). In patients taking Eliquis, the rates of post-procedural stroke or systemic embolism and major bleeding were similar whether Eliquis was interrupted or continued. In patients taking warfarin, the rates of post-procedure major bleeding and death appeared higher when warfarin was continued compared to when it was interrupted.

“The current results do not include analyses for individual procedure types and therefore decisions whether to interrupt apixaban or warfarin prior to procedures should be based on consideration of procedural bleeding risk and patient thrombotic risk,” said Dr Lopes. “In addition, further analyses, including analyses according to type of procedures and timing, are ongoing to better define these relationships.”

The ARISTOTLE study was designed to demonstrate the efficacy and safety ofEliquis versus warfarin for the prevention of stroke or systemic embolism. In ARISTOTLE, 18,201 patients were randomized (9,120 patients to Eliquis and 9,081 to warfarin). ARISTOTLE was an active-controlled, randomized, double-blind, multi-national trial in patients with nonvalvular atrial fibrillation or atrial flutter, and at least one additional risk factor for stroke. Patients were randomized to treatment with Eliquis 5 mg orally twice daily (or 2.5 mg twice daily in selected patients, representing 4.7 per cent of all patients) or warfarin (target INR range 2.0-3.0), and followed for a median of 1.8 years.

Eliquis (apixaban) is an oral direct Factor Xa inhibitor. By inhibiting Factor Xa, a key blood clotting protein, Eliquis prevents thrombin generation and blood clot formation. Eliquis is approved to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation in the United States, European Union (which includes 28 member states plus Iceland and Norway), Japan and a number of other countries around the world. Eliquis is approved for prevention of venous thromboembolic events (VTE) in adult patients who have undergone elective hip or knee replacement surgery in the European Union (which includes 28 member states plus Iceland and Norway) and a number of other countries around the world. Eliquisis not approved for this indication in the US or Japan.

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