Balancing safety and efficacy: Factor XIa inhibitors vs. DOACs in atrial fibrillation: a systematic review and meta-analysis of randomised controlled trials

Current ESC guidelines recommend the use of oral anticoagulant therapy in patients with atrial fibrillation to reduce the risk of arterial embolization, however, the performance of different oral anticoagulants (OACs) in terms of bleeding risk is still scarce. Recently, Factor XIa inhibitors became an alternative to the commonly used direct oral anticoagulants (DOACs).

This systematic review and meta-analysis of randomized controlled trials aims to assess whether Factor XIa inhibitors lead to lower risks of bleeding compared to DOACs in patients with atrial fibrillation.

PubMed, Cochrane, and EMBASE were searched. The primary endpoint was the occurrence of a composite of major or clinically relevant non-major bleeding. Secondary endpoints included death from any cause, cardiovascular death, any adverse effects, any serious adverse effects, minor bleeding, stroke, or systemic embolism. A random-effect model was used to calculate the risk ratio (RR) with a 95% confidence interval (CI).

A total of 3 RCTs met the inclusion criteria and were included in the qualitative and quantitative analysis comprising 16,959 patients. Factor XIa inhibitors were associated with significantly fewer major or clinically relevant non-major bleedings than DOACs (RR = 0.39 [95% CI [0.22, 0.70]), I²= 19%, P< 0.00001). There were no differences between Factor XIa inhibitors and DOACs regarding the occurrence of death (RR = 0.86 [95% CI 0.78, 0.95]), I² = 0%, (P = 0.28) , cardiovascular death (RR = 1.09 [95% CI 0.77, 1.55]), I² = 0%, (P = 0.65) and any adverse effects (RR=1.00 [95% CI 0.97, 1.04],I² = 0%, (P=0.87). Interestingly the risk of stroke and systemic embolism was higher among the patients exposed to factor XIa inhibitors compared to the DOACs group RR = 2.89 [95% CI [0.88, 9.50]), I² = % 26%, (P = 0.0005). Conversely, minor bleedings were more common in the DOACs arm (RR = 0.58 [95% CI [0.26, 1.29]), I² = 0%, (P < 0.00001).

Factor XIa inhibitors are superior to DOACs in terms of bleeding complications. However, this meta-analysis shows a significantly higher risk of stroke or systemic embolism as compared to commonly used DOACs.

Primary Endpoint