Background: Current ESC guidelines recommend the use of oral anticoagulant therapy in patients with atrial fibrillation to reduce the risk of arterial embolization. Recently, Factor XIa inhibitors were investigated as an alternative to the commonly used DOACs. Aims: This systematic review and meta-analysis aim to assess whether Factor XIa inhibitors lead to lower risks of bleeding compared to DOACs in patients with atrial fibrillation. Methods: 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. Results: A total of 3 studies met the inclusion criteria and were included in the qualitative and quantitative analysis, comprising 16,772 patients. Factor XIa inhibitors were associated with significantly fewer major or clinically relevant non-major bleedings than DOACs (RR = 0.40 [95% CI [0.32, 0.51]), I² = 3%, p < 0.00001). There were no differences between Factor XIa inhibitors and DOACs regarding the occurrence of death (RR = 0.83 [95% CI 0.63, 1.08]), I² = 0%, (p = 0.15) and cardiovascular death (RR = 1.09 [95% CI 0.74, 1.63]), I² = 0%, (p = 0.65). Interestingly, the risk of stroke and systemic embolism was higher among the patients exposed to factor XIa inhibitors compared to the DOACs group RR = 6.05 [95% CI [1.02, 35.94]), I² = 5%, (p = 0.05). Conclusions: 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.

Healing after transmetatarsal amputation (TMA) depends on adequate tissue perfusion. Revascularization prior to minor amputation improves amputation-free survival, limb preservation, and wound healing in patients with ischemic wounds. However, the optimal interval between revascularization and amputation remains unclear. The TriNetX real-world clinical data platform was used to identify patients with chronic limb-threatening ischemia (CLTI) who underwent endovascular revascularization followed by TMA. Patients were categorized into early TMA (≤7 days after revascularization) and late TMA (8-30 days). Propensity score matching was performed using demographics, comorbidities, laboratory values, and concurrent therapies. Major amputation and all-cause mortality at 6 months and 1 year were evaluated using Cox proportional hazards models. Kaplan-Meier curves and log-rank tests were used for time-to-event analyses. Among 700 patients with CLTI treated with revascularization before TMA, 508 underwent early TMA and 192 underwent late TMA. After matching, 185 patients remained in each group (96.3% match rate). The mean age was 66.9 ± 10.9 years, 78.1% were male, and mean follow-up was 237.2 days. At 6 months, major amputation (hazard ratio [HR], 0.87; 95% CI, 0.51-1.46; P =.597) and all-cause mortality (HR, 0.74; 95% CI, 0.45-1.20; P = .220) did not differ between groups. At 1-year, major amputation (HR, 0.87; 95% CI, 0.52-1.45; P = .599) and mortality (HR, 0.73; 95% CI, 0.46-1.14; P = .164) also remained similar. A composite endpoint of major amputation or all-cause mortality was also similar between groups (HR, 0.995; 95% CI, 0.694-1.425; P = .978). Among patients with CLTI undergoing endovascular therapy and subsequent TMA, early (≤7 days) vs late (8-30 days) amputation timing did not significantly affect major amputation or survival outcomes.