open access publication

Article, 2023

Initiation of warfarin is associated with decreased mortality in patients with infective endocarditis: A population-based cohort study

Thrombosis Research, ISSN 0049-3848, 1879-2472, Volume 233, Pages 1-9, 10.1016/j.thromres.2023.11.009

Contributors

Lee, Teddy Tai Loy 0000-0001-9688-1348 [1] [2] Chan, Sunny Ching-Long [2] Chou, Oscar Hou In 0000-0001-7058-4708 [2] [3] Lee, Sharen 0000-0002-2401-2837 [4] Chan, Jeffrey Shi Kai 0000-0003-0231-2393 [5] Liu, Tong- 0000-0003-0482-0738 [6] Chang, Carlin [2] Wong, Wing Tak J 0000-0002-3453-1825 [7] Lip, Gregory Y H [8] [9] Cheung, Bernard Man Yung [2] Wai, Abraham Ka Chung 0000-0001-9984-8156 (Corresponding author) [2] Tse, Gary Man-Kit 0000-0001-5510-1253 (Corresponding author) [6] [10] [11]

Affiliations

  1. [1] Department of Emergency Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China; Cardiovascular Pharmacology Unit, Cardiovascular Analytics Group, PowerHealth Research Institute, Hong Kong, China. Electronic address: teddywlee88@gmail.com.
  2. [NORA names: China; Asia, East];
  3. [2] University of Hong Kong
  4. [NORA names: China; Asia, East];
  5. [3] Cardiovascular Pharmacology Unit, Cardiovascular Analytics Group, PowerHealth Research Institute, Hong Kong, China; Division of Clinical Pharmacology, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China. Electronic address: oscarjx1@connect.hku.hk.
  6. [NORA names: China; Asia, East];
  7. [4] Cardiovascular Pharmacology Unit, Cardiovascular Analytics Group, PowerHealth Research Institute, Hong Kong, China. Electronic address: sharen212@gmail.com.
  8. [NORA names: China; Asia, East];
  9. [5] Cardiovascular Pharmacology Unit, Cardiovascular Analytics Group, PowerHealth Research Institute, Hong Kong, China. Electronic address: jeffreychan.dbs@gmail.com.
  10. [NORA names: China; Asia, East];

Abstract

IMPORTANCE: The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. DESIGN: Population-based retrospective cohort study. PARTICIPANTS: Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 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). 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 hemorrhage (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 hemorrhage 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: Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, 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 hemorrhage, 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 hemorrhage.

Keywords

Competing risk regression, Cox, Cox regression, Fine-Gray, Fine-Gray regression, Hong, Hong Kong, IE diagnosis, Kong, Thirty-day, all-cause mortality, analysis, associated with decreased mortality, baseline, baseline characteristics, benefits, bleeding, bleeding risk, characteristics, cohort, cohort study, cumulative incidence, cumulative incidence of intracranial hemorrhage, days, days of diagnosis, days of follow-up, decrease, decreased risk, decreased risk of mortality, diagnosis, diagnosis of infective endocarditis, endocarditis, events, follow-up, gastrointestinal bleeding, group, hazard, hazard ratio, hemorrhage, high risk, high risk of intracranial hemorrhage, incidence of intracranial hemorrhage, increased bleeding risk, increased risk, increased risk of intracranial hemorrhage, infective endocarditis, initiation, initiation of warfarin, intracranial hemorrhage, ischaemic stroke, ischemic stroke, landmark analysis, landmarks, matched cohort, matching, mortality, mortality benefit, non-users, outcome of ischemic stroke, outcomes, patients, population-based, population-based cohort study, propensity, propensity score matching, prospective cohort study, questions, ratio, regression, relevance, results, risk, risk of all-cause mortality, risk of intracranial hemorrhage, risk of ischaemic stroke, risk of ischemic stroke, risk of mortality, risk regression, score matching, sensitivity, sensitivity analysis, stroke, study, thromboembolism, treatment, treatment groups, use, users, warfarin, warfarin non-use, warfarin use, warfarin users

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