Background: Secondary atrial fibrillation (AF), triggered by reversible conditions such as hyperthyroidism, non-cardiac surgery and sepsis, is a common clinical challenge among hospitalized patients and is associated with considerable morbidity and mortality. However, the optimal anticoagulation strategy remains uncertain. Anticoagulation offers potential stroke prevention benefits, but carries a risk of bleeding, underscoring the need for clear, evidence-based recommendations. This systematic review and meta-analysis aimed to evaluate the risks and benefits of anticoagulation in patients with secondary AF related to hyperthyroidism, non-cardiac surgery and sepsis.
METHODS AND RESULTS: Methods Following PRISMA guidelines, we systematically searched four databases (Cochrane, Embase, MEDLINE, PubMed) using a combination of text words and indexed terms. Search strategies were peer-reviewed by two independent librarians. Eligible studies included randomized controlled trials and observational studies involving adults with new-onset secondary AF due to non-cardiac surgery, sepsis, or hyperthyroidism. Primary outcomes included thromboembolic events, bleeding, and mortality. Three reviewers (KH, DJ, GW) independently screened studies, performed quality assessment using the NIH study quality assessment tool, and extracted data. Pooled risk ratios (RRs) were calculated using a random-effects model in SPSS statistical analysis software.
Results The search yielded 13,921 articles. Ultimately, 13 studies met inclusion criteria, with 3 additional studies identified using forward and backward citation tracking, resulting in a total of 16 studies encompassing 75,894 patients. All studies were observational in nature: one was prospective, and the remaining were retrospective. To minimize the risk of bias, 7 studies that did not adjust their outcomes for confounding variables, such as age, sex, comorbidities, etc., were excluded from the meta-analysis. Anticoagulation was associated with a significant reduction in stroke, transient ischemic attack (TIA), or systemic embolism (RR 0.76; 95% CI, 0.64-0.90), with consistent findings across subgroups (hyperthyroidism, post non-cardiac surgery, sepsis). Anticoagulation was also linked to reduced mortality in all groups (RR 0.53, 95% CI, 0.45-0.62). Bleeding risk was not significantly increased in both the sepsis (RR 1.0, 95% CI, 0.85-1.16) and postoperative (RR 1.36, 95% CI, 0.96-1.92) cohorts. However, important heterogeneity was observed across studies, as indicated by I^2 testing.
Conclusion: In patients with secondary AF, anticoagulation appears to confer significant reductions in both thromboembolic events and all-cause mortality without a corresponding increase in bleeding risk. Nevertheless, due to the observational nature and heterogeneity of the current evidence, high-quality randomized controlled trials are essential to establish definitive treatment recommendations for this diverse and high-risk population.
