Sex-influence on the time in therapeutic range (TTR) during oral anticoagulation with coumarin derivatives: Systematic review and meta-analysis

Br J Clin Pharmacol. 2021 Dec;87(12):4488-4503. doi: 10.1111/bcp.14892. Epub 2021 May 26.

Abstract

Aims: We sought to investigate the association between sex and oral anticoagulation control employing coumarin derivatives.

Methods: Electronic sources were MEDLINE, Biblioteca Virtual em Saúde (BVS), The Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central and Web of Science. Inclusion criteria were: observational and experimental studies; age ≥18 years; both sexes; treatment with any coumarin derivative for ≥3 months; any indication of long-term use; quality of oral anticoagulation measured by time in therapeutic range (TTR). The meta-analysis was developed with odds ratios (OR) for binary variables and mean differences (MD) for continuous variables, using random-effects models (DerSimonian and Laird) with 95% confidence intervals (CI).

Results: Overall, 22 articles were selected, comprising 16 cohort studies, four cross-sectional studies and two clinical trials. The number of participants ranged from 110 to 104 505 (183 612; women: 45%). The main indication of oral anticoagulation was atrial fibrillation. Most studies reported the use of warfarin. In the meta-analysis, 15 studies were analysed using TTR as a binary variable (OR = 0.87; 95% CI = 0.78, 0.96; z = -2.75; P = .006.; I2 = 67%) and seven studies as a continuous variable (MD = -2.97; 95% CI = -4.80, -1.14; z = -3.19; P = .0014; I2 = 75%). The pooled estimates indicated that women were associated with lower TTR than men.

Conclusions: Our findings revealed an association between female sex and worse oral anticoagulation control. Further studies are needed with primary design to investigate sex-related factors influencing oral anticoagulation control with coumarin derivatives. Innovative strategies focused on women's health may be useful to improve patient-centred care.

Keywords: coumarins; quality of health care; sex; thromboembolism; warfarin.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Anticoagulants
  • Atrial Fibrillation* / drug therapy
  • Blood Coagulation
  • Coumarins* / pharmacology
  • Coumarins* / therapeutic use
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Warfarin

Substances

  • Anticoagulants
  • Coumarins
  • Warfarin