Factors associated with nonadherence to the use of coumarin derivatives or direct oral anticoagulants: A systematic review of observational studies.

Nonadherence to thromboprophylaxis treatment with oral anticoagulants (OAC) is a public health problem and may be associated with high mortality rates. We sought to synthesize the factors associated with nonadherence to therapy with coumarin derivatives or direct oral anticoagulants. A systematic review was performed at electronic databases Medline, Embase, CINAHL, Lilacs and grey literature (Google Scholar, MedNar, OpenGray, ProQuest Dissertations and Theses, and hand search). This study was conducted according to Cochrane's method and PRISMA. The registration on PROSPERO is CRD42020223555. Overall, 1270 studies were identified and nine studies were selected for this review. In hand searching, 77 studies were found, but none included. The associated factors with nonadherence were heterogeneous, and some factors were described as both risk and protection for nonadherence, with few variables showing consistent results among the studies. Variables reported only as risk factors were "male sex", "hospitalization", "Charlson score" and "bleeding", while "white race", CHA2 DS2 VASc (score range 2-9)" and "polypharmacy" were reported only as protective factors. Most studies did not present details in the description of concepts and methods to assess nonadherence. In clinical practice, the knowledge on factors associated with nonadherence is helpful to identifying patients at higher risk of complications that would benefit from individualized interventions.

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

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.