Initiation of Warfarin is associated with Decreased Mortality in Patients with Infective Endocarditis: A Population-Based Cohort Study

Abstract Importance The use of warfarin as an anticoagulant to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. Objective This study compared the risks of ischemic stroke, death and bleeding in patients with IE with and without warfarin use. Design Prospective cohort study. Setting Population-based. Participants Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1 st 1997 and August 31 st 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. Exposure Warfarin use within 14 days of IE diagnosis. Main outcomes and measures Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95% confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. Results The matched cohort consisted of 675 warfarin users (57.0% male, age 59±16 years) and 675 warfarin non-users (53.5% male, age 61±19 years). From Cox regression, warfarin users had a 50% decreased 90-day risk in all-cause mortality (HR: 0.50 [0.39-0.65]), without significantly different 90-day risks of ischemic stroke (HR: 1.04 [0.70-1.53]), intracranial haemorrhage (HR: 1.25 [0.77-2.04]), and gastrointestinal bleeding (HR: 1.04 [0.60-1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial haemorrhage in warfarin users (sub-HR: 3.34 [1.34-8.31]), but not at 90-day (sub-HR: 1.63 [0.95-2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. Conclusions and relevance In patients with IE, warfarin use initiated within 14 days of IE diagnosis may be associated with significantly decreased risks of mortality but higher risks of intracranial haemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. Key points Question Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe? Findings In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50% decrease in the risk of all-cause mortality, albeit with higher risk of intracranial haemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial haemorrhage.