Effects of Warfarin on the Risks of Mortality, Acute Heart Failure, and Infection Resolution in Patients With Infective Endocarditis: A Target Trial Emulation

BACKGROUND: Infective endocarditis (IE) can be complicated by acute heart failure and bacteremia, which can account for increased mortality. The role of anticoagulation with warfarin in IE is controversial. This study aimed to study the effects of anticoagulation with warfarin on survival in patients with IE, through reducing the risks of thromboembolism and possibly shortening infection time. METHODS: This was a retrospective population-based cohort study using the Clinical Data Analysis and Reporting System from Hong Kong. Patients diagnosed with IE between January 1, 1997 and August 31, 2020 were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes. A target pragmatic trial was emulated using the observational data with cloning-censoring-weighting approach, comparing the treatment effect of initiation warfarin within 14 days versus no warfarin on the risk of all-cause mortality, acute heart failure, and achieving negative blood culture in patients with IE. Pooled logistic regression was applied to estimate 12-week survival or cumulative incidence differences and risk ratios (RRs). RESULTS: A total of 5121 patients with IE with an average age of 55.7 years (SD:18.9) were included. Warfarin use was associated with lower risks of all-cause mortality with 12-week survival difference of 6.5% (95% CI, 2.6%–9.9%) and RR of 0.72 (95% CI, 0.57–0.88) and a greater benefit of achieving negative blood cultures with 12-week cumulative incidence difference of 11.4% (95% CI, 5.4%–16.5%) and RR of 1.13 (95% CI, 1.06–1.20) but similar risks of acute heart failure (RR, 1.07 [95% CI, 0.87–1.30]). CONCLUSIONS: Patients with IE initiating warfarin had significantly lower risk of mortality with potential benefits on achieving negative blood cultures, suggesting benefit in infection resolution but a similar risk of acute heart failure.