Efficacy of anticoagulation in atrial fibrillation: evidence from 36 years of randomized controlled trials - a meta-analysis

Abstract Background Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is a major health concern due to its association with thromboembolic complications, warranting the use of anticoagulants as a primary preventive strategy. Although its use reduces the risk of ischemic stroke and systemic embolism, it also increases the risk of bleeding. Recent research indicates that the real risk of stroke in patients with untreated AF is decreasing and it is lower than predicted by the CHA2DS2–VASc score. Purpose We conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the effectiveness of anticoagulation in AF patients, contextualizing findings on light of recent evidence showing that untreated patients with AF now have a lower baseline stroke risk than historically predicted. Methods We search Pubmed, Embase and Cochrane databases for RCTs that determined the effectiveness of the use of anticoagulants, directed oral anticoagulants (DOACs) or warfarin, versus placebo or antiplatelets in patients with AF in reducing ischemic stroke, transient ischemic attack (TIA) and systemic embolism was assessed, along with the risk of cardiovascular death. Data were pooled in risk ratio (RR) using a random-effects model and the confidence interval (CI) was assumed to be 95%. Heterogeneity was calculated using I2. Statistical analysis was made using RStudio (version 4.2.2). Results We identified 18 RCTs in 36 years of tracking, with a total of 36,006 patients. The mean age was 72.6 ± 9.1 years and 40.2% were female. The use of anticoagulation (DOACs or warfarin) significantly reduced the risk of ischemic stroke (RR 0.42; 95% CI 0.34 - 0.51; p 0.001; I2 31.3%, Fig 1A) and systemic embolism (RR 0.38; 95% CI 0.25 - 0.58; p 0.001; I2 0%, Fig 1B) compared with control. However, there was no significant difference in TIA rates (RR 0.64; 95% CI 0.34 - 1.22; p 0.17; I2 0%, Fig 2A), cardiovascular death (RR 1.02; 95% CI 0.79 - 1.31; p 0.89; I2 22.9%, Fig 2B) or all-cause of death (RR 0.97; 95% CI 0.87 - 1.09; p 0.63; I2 7.9%, Fig 2C) between the groups. Notably, the analysis revealed low heterogeneity across studies and null differences in mortality outcomes. Conclusions This large meta-analysis shows that anticoagulation in AF patients reduces rates of ischemic stroke and systemic embolism, without changing the incidence of TIA, cardiovascular death and all-cause of death. As evolving medical technologies and shifting clinical practices continue to influence patient outcomes over the decades, updated, large-scale RCTs are required. New trials are needed to reassess risk profiles and the overall benefit-risk ratio in the modern era, with a view to informing optimized treatment strategies in atrial fibrillation management.A - Stroke / B - Sistemic Embolism A- TIA / B- Cardio Death / C- All Death