Waqas, Saad Ahmad

ABSTRACT Background Factor XI/XIa inhibitors are emerging anticoagulants with potential to reduce bleeding complications in atrial fibrillation (AF) patients. This meta‐analysis evaluated their efficacy and safety compared to direct oral anticoagulants (DOACs) and explored dose optimization. Methods A systematic search of PubMed, Cochrane, and Embase was conducted through March 2025 following PRISMA guidelines. Randomized controlled trials (RCTs) comparing Factor XI/XIa inhibitors with DOACs in AF patients were included. Outcomes assessed were major bleeding, stroke, systemic embolism, all‐cause and cardiovascular mortality and serious adverse events. Risk ratios (RR) with 95% confidence intervals (CI) were pooled using a Mantel‐Haenszel random‐effects model. Heterogeneity was evaluated with the I² statistic, and evidence certainty assessed by the GRADE approach. Trial Sequential Analysis (TSA) was performed. Results Three RCTs including 16,772 patients (mean age 73 years, CHA₂DS₂‐VASc 3.9–5) were analyzed. Factor XI/XIa inhibitors significantly reduced major bleeding (RR: 0.41, 95% CI: 0.36–0.46, I² = 0%) compared to DOACs. However, stroke risk was increased (RR: 3.42, 95% CI: 2.62–4.46), particularly with asundexian 50 mg (RR: 4.02). No significant differences were observed in all‐cause mortality (RR: 0.82) or cardiovascular death (RR: 1.05). Systemic embolism risk was higher (RR: 4.26), while serious adverse events were comparable (RR: 0.95). TSA indicated encouraging safety outcomes but highlighted the need for further large‐scale studies. Conclusion Factor XI/XIa inhibitors lower major bleeding risk in AF patients but increase stroke and systemic embolism rates without impacting mortality.

Despite advances in percutaneous coronary procedures, in-stent restenosis remains a significant challenge. Although sirolimus- and paclitaxel-coated balloons are promising alternatives, their comparative safety and efficacy remain uncertain. PubMed, Embase, and Cochrane databases were searched using relevant keywords from inception until August 2025. A total of 11 studies (7 randomized controlled trials and 4 observational cohort studies) were included, comprising 3633 participants overall. The primary outcomes assessed were target lesion revascularization and target lesion failure. Meanwhile, the Secondary outcomes included stent thrombosis, all-cause mortality, myocardial infarction, major adverse cardiovascular events, survival, binary restenosis, and angiographic endpoints (acute gain, diameter stenosis, in-segment late lumen loss, in-lesion late lumen loss, and in-segment minimal lumen diameter). Interstudy heterogeneity was assessed using I ² and X ² statistics ( I ²>50% = significant heterogeneity). Interstudy heterogeneity was low for most outcomes, including all primary clinical endpoints, with moderate heterogeneity observed only for select angiographic measures (notably in-segment late lumen loss and diameter stenosis). Statistical analysis was conducted using R software and RStudio (version 4.4.2), with a P value of < 0.05 indicating statistical significance. This meta-analysis examined studies that compared paclitaxel-coated balloon (PCB) versus standard balloon [sirolimus-coated balloon (SCB)] angioplasty. Regarding primary outcomes, there were no notable variations in target lesion failure [risk ratio (RR), 1.08, 95% CI, 0.90–1.29, P = 0.36] or target lesion revascularization (RR, 1.16, 95% CI, 0.98–1.37, P = 0.08). With all aggregated estimates being nonsignificant, secondary outcomes such as stent thrombosis, all-cause mortality, myocardial infarction, major adverse cardiovascular events, and survival were similar between groups. Angiographic endpoints revealed no discernible variations in late lumen loss (in-lesion and in-segment), acute gain, or diameter stenosis. Nonetheless, the SCB group’s minimal lumen diameter was significantly smaller than that of the PCB group (MD, −0.08 mm, 95% CI, −0.14 to −0.01, P = 0.02). In treating coronary in-stent restenosis, SCB and PCBs show similar overall safety and effectiveness; lesion-specific angiographic variations indicate that customized selection may improve patient outcomes.