Apixaban’s benefit preserved across risk categories

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 - clinical trial

The anticoagulant apixaban reduced the risk of stroke and bleeding in patients with nonvalvular atrial fibrillation (AF) and at least one risk factor for stroke without regard to the patients’ scores on the CHADS 2, CHA 2DS2VASc and HAS-BLED scales, according to a study published online Oct. 2 in Lancet.

This a secondary finding of the Apixaban Reduction in Stroke and Other Thrombolytic Events in Atrial Fibrillation (ARISTOTLE) trial, according to the study's lead author, Renato D. Lopes, MD, of the Duke Clinical Research Institute in Durham, N.C. Results of the ARISTOTLE trial were presented in 2011 at the European Society of Cardiology.

ARISTOTLE is a double-blind, randomized trial that enrolled 18,201 patients from 39 countries who were experiencing AF and one or more risk factors for stroke. Patients received either 5 mg of apixaban (Eliquis, Bristol-Myers Squibb/Pfizer) twice daily or warfarin.

The ARISTOTLE data showed patients who received treatment with apixaban experienced significant additional relative reductions in stroke or systemic embolism (21 percent), major bleeding (31 percent) and overall mortality (11 percent) when compared with patients who were treated with warfarin. Furthermore, fewer patients on apixaban ceased treatment prematurely, “which suggests that apixaban is better tolerated than warfarin,” Lopes said in an interview with Cardiovascular Business.

In the secondary analysis, researchers evaluated the relative effectiveness of apixaban, an oral direct factor Xa inhibitor, in treating patients at various levels of risk of stroke and bleeding. “It was possible that in some of the risk categories, results might differ. But we found that the benefit [of apixaban] was preserved regardless of risk score across all categories,” Lopes said .

Significantly, the greatest overall reduction in intracranial bleeding was seen in patients who scored three or higher on the HAS-BLED scale. “The magnitude of the benefit [of apixaban treatment] was greatest in the patients at highest risk of bleeding, the patients we are most concerned about treating with anticoagulant therapy. Apixaban is an attractive option for these patients,” Lopes said.

He explained that the results have important implications for clinicians treating all AF patients at risk of stroke. “The risk scoring systems are very good in terms of their ability to predict events. The main problem is that the variables in the different scoring categories overlap ... and so they do not give a threshold that helps physicians to design a therapy.”

Because apixaban is effective across all risk categories and every degree of risk, physicians will be relieved of the necessity of attempting to balance stroke and bleeding risk factors when developing a treatment plan,  Lopes said.

Currently, apixaban is not approved for any use in the U.S. The FDA has set a new goal date of March 17, 2013, to review its New Drug Application. The FDA has already extended the review date goal several times.

Apixapan in approved for use in 27 EU countries for the prevention of venous thrombolytic events in adults electing knee and hip replacement surgery. The Committee for Medicinal Products for Human Use of the European Medicines Agency recently recommended approval of apixapan for the prevention of strokes and systemic embolism in adult patients with nonvalvular AF and one or more risk factors for stroke. The recommendation must be reviewed by the European Union before the drug is approved for that use in the 27 EU member states.