Lowering Factor XI to Prevent Thromboembolism

David Green, MD, PhD

Reducing levels of factor XI provides some protection without inducing excessive bleeding.

Reduced levels of clotting factor XI might offer protection against venous thromboembolism (VTE) and are generally associated with only a mild bleeding tendency. A specific antisense oligonucleotide (FXI-ASO) has been developed that decreases factor XI messenger RNA expression in the liver.

To determine if FXI-ASO decreases VTE in patients undergoing total-knee arthroplasty, investigators conducted a multicenter, randomized, open-label, phase II trial in which 72 patients received enoxaparin (40 mg once daily for ≥8 days), 144 patients received 200-mg doses of FXI-ASO, and 77 patients received 300-mg doses of FXI-ASO. FXI-ASO doses were given subcutaneously 3 or 4 times weekly beginning 36 days prior to surgery, were held during the week before surgery, and were given 6 and 72 hours postoperatively. Bilateral venography was performed 8 to 12 days after surgery, and patients were followed for 3 months thereafter.

Perioperative FXI levels in the enoxaparin, 200-mg FXI-ASO, and 300-mg FXI-ASO groups were 0.93, 0.38, 0.20 U/mL, respectively. VTE occurred in fewer patients in the 300-mg FXI-ASO group versus the enoxaparin group (4% vs. 30%; P<0.001); the 200-mg regimen of FXI-ASO was noninferior to enoxaparin (27% vs. 30%). Major or clinically relevant non-major bleeding and the frequency of blood transfusions were similar among the three groups. Injection site reactions were more common in those receiving FXI-ASO.

Citation(s):

Büller HR et al. Factor XI antisense oligonucleotide for prevention of venous thrombosis. N Engl J Med 2014 Dec 7; [e-pub ahead of print].