Background The assessment of adherence to warfarin therapy is useful in clinical practice due to its wide variability in dose-response and risks of complications. The aim of this study was to investigate validated instruments used to assess adherence to warfarin therapy. Methods Information was collected from the MEDLINE (PubMed), LILACS, EMBASE, and Cochrane Library databases. Search strategies were applied for each database, with no time limit or language restriction. Inclusion criteria consisted of study participants of ≥ 18 years of age, from both sexes, on chronic anticoagulation with warfarin for any indication and the use of validated instruments to assess adherence to warfarin therapy. Exclusion criteria consisted of duplicate articles, narrative or systematic reviews, and meta-analyses, as well as case reports/series and experimental studies involving animals. Two independent reviewers performed the following steps: evaluation of titles/abstracts, selection of studies after full reading, data extraction, and evaluation of potential bias. Discrepancies were resolved by a third reviewer. Results Overall, 19 articles were selected for this systematic review, including 17 cross-sectional studies, one cohort study, and one quasi-experimental study, published from 2009 to 2019. The validated instruments identified in this review were Morisky Medication Adherence Scale (MMAS), the eight-item Morisky Medication Adherence Scale (MMAS-8), Measurement of Treatment Adherence (MTA), and Brief Medication Questionnaire (BMQ). Only MMAS-8 was tested for reliability, using the internal consistency assessment, with Cronbach's α range 0.56-0.71. Conclusions This review highlighted a gap in knowledge regarding the scarcity of validated instruments to assess adherence to warfarin therapy. Limitations were found in instruments that comprised the assessment of the isolated use of medication and the lack of analysis of other relevant therapeutic aspects. Future studies are needed to develop and validate more comprehensive instruments in an attempt to assess adherence to warfarin therapy. PROSPERO Registration number CRD42019128324 Keywords Anticoagulants • Medication Adherence • Validation studies • Warfarin Key points• Adherence to prescribed drugs is currently a major obstacle for outpatients to achieve success in drug therapy. The assessment of adherence behaviors is useful to substantiate intervention strategies that seek to bring about changes in health outcomes as a consequence of drug therapies. • No adapted and validated instruments addressing specificities of warfarin therapy were found in this review. Current instruments to assess adherence to warfarin therapy address the isolated use of the medication with no items covering other relevant aspects of therapy, such as diet and drug interactions. • Further studies are needed to investigate specific scales in order to evaluate adherence to warfarin therapy, employing the assessment of their psychometric properties and applicability in clinical practiceExtended author inf...

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 crosssectional 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 = À2.75; P = .006.; I 2 = 67%) and seven studies as a continuous variable (MD = À2.97; 95% CI = À4.80, À1.14; z = À3.19; P = .0014; I 2 = 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.

This review will aim to assess the influence of sex-based differences on oral anticoagulation control in patients taking coumarin derivatives. Introduction:Coumarin derivatives, such as warfarin, have a narrow therapeutic index, requiring frequent monitoring to achieve adequate anticoagulation control, which can be assessed by the time in therapeutic range. Differences in the quality of oral anticoagulation control between men and women have been reported, although the current evidence is controversial. A systematic review on this topic would provide results that could be incorporated into clinical practice to enhance oral anticoagulation control and treatment outcomes.Inclusion criteria: Observational and experimental studies were assessed for eligibility, with participants aged !18 years of either sex taking oral anticoagulation or other coumarin derivatives for !3 months, for any indication of chronic use, who had oral anticoagulation control evaluated by time in therapeutic range.Methods: Electronic databases to be searched include MEDLINE, BVS, CINAHL, Embase, Cochrane CENTRAL, and Web of Science. Two reviewers will independently perform title/abstract selection and screening, and then full text retrieval and screening of articles that meet the inclusion criteria. The evaluation of methodological quality and data extraction will also be performed by two independent reviewers. Data will be synthesized in tables and then the compiled results will be meta-analyzed. In the presence of subgroup differences, meta-regression methods will be used to investigate the effects of categorical or continuous covariates. If statistical pooling is not possible, a narrative synthesis will be presented.

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", CHA 2 DS 2 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.

The present study aimed to investigate the relationship between the level of patient knowledge on warfarin therapy and the quality of oral anticoagulation. This is a systematic review and meta-analysis written on the basis of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Searches at MEDLINE, EMBASE, Scopus and LILACS electronic databases were carried out on February 13, 2023, using the descriptors "Patient Medication Knowledge", "Patient Education as Topic", "Health Education", "Patient Education" and Warfarin. The steps of selection, data extraction and quality analysis of articles were performed independently by two reviewers. The analysis was performed considering patient knowledge as a possible modifier of time in therapeutic range (TTR). The meta-analysis included studies that reported the correlation coefficient (Pearson or Spearman) between patient knowledge and TTR. A subgroup analysis was performed according to questionnaires employed to measure patient knowledge. Twelve studies were selected with an overall sample size of 7634 participants and mean age 58.2 (standard deviation (SD)±12,8) years. Eleven (92.0%) cross-sectional studies. The mean TTR was 57.8% (SD±11,3%) and the average level of knowledge was 60.4%. The meta-analysis indicated that patient level of knowledge on warfarin therapy was moderately associated with TTR (rs = 0.435; 95% confidence interval (CI) = 0.163–0.645; I2 = 96%). Subgroup analysis indicated association between knowledge level and TTR in studies employing the OAK test (rs = 0.617; 95% CI = 0.192–0.847; I2 = 97%) and the AKA (rs = 0.269; 95% CI = 0.002 to 0.501; I2 = 94%). However, the subgroup analysis presented no significant difference between them (p = 0.14). The meta-regression showed a non-significant negative effect of age on the correlation (estimate = -0.028, 95% CI = -0.073 to 0.016, p = 0.207). No publication bias was noted (p = 0.881). To our knowledge, this is the first systematic review and meta-analysis gathering evidence about the relationship between the level of patient knowledge on oral anticoagulation with warfarin and TTR. The implementation of structured and patient-centered educational interventions is essential to effectively increase the level of patient knowledge and, thus, to improve the quality and safety of warfarin therapy. Systematic review registration number: PROSPERO CRD42023398030.

Introduction: Sex-differences in the quality of oral anticoagulation control have been reported,although with controversial evidence. Our hypothesis was that sex would be associated withoral anticoagulation control. We performed a systematic review and meta-analysis to investigatethis association. Methods: We searched for studies on MEDLINE, BVS, CINAHL, EMBASE,Cochrane and Web of Science. We included observational and experimental studies withparticipants aged >18 years of both sexes, on oral anticoagulation with warfarin or othercoumarin derivatives indicated for long-term use. The outcome of interest was time intherapeutic range (TTR), calculated by the Rosendaal method. We synthesized data from theselected studies and developed the meta-analysis. Odds ratios (OR) for binary variables andmean differences (MD) for continuous variables were pooled using the random-effects modelswith estimation via the DerSimonian-Laird method. Results: Thirteen studies with 89,745patients (45.08% women) were included. Nine studies were assessed in the meta-analysis frombinary variables (OR=0.89; 95% CI=0.80, 1.00; z=-1.96; p=0.05; I 2 =74%) (Fig. 1) and fourstudies with continuous variables (MD=-3.02; 95% CI=-4.43, -1.62; z=-4.22; p<0.0001; I 2 =0%)(Fig. 2). The pooled estimates indicated that women were associated with lower TTR than men. Fig. 1 Analysis of sex effect on oral anticoagulation control. Fig. 2 Analysis of sex effect on oral anticoagulation control. In conclusion, this systematic review showed that the female sex was associated with lowerTTR than male sex. Our results suggest the need for innovative strategies to improve healthcarefocused on women.

Objetivo: Descrever fatores associados à não adesão ao uso de derivados cumarínicos e anticoagulantes orais de ação direta.Método: Serão elegíveis os estudos observacionais e experimentais, com pacientes ≥ 18 anos em anticoagulação oral. A busca deartigos será nas bases MEDLINE (via PubMed), EMBASE, CINAHL e Literatura Latino-Americana e do Caribe, além de busca manualnas listas de referência dos estudos selecionados. As duplicatas serão removidas. Será feita leitura do título/resumo dos artigospara pré-seleção daqueles que serão lidos na íntegra para definir sobre sua inclusão na revisão. As informações serão extraídas,tabuladas e descritas de forma narrativa. Resultado: Na busca preliminar foram encontrados 1270 estudos, sendo selecionados 21artigos para a revisão sistemática após realização das etapas metodológicas. Conclusão: O conhecimento dos fatores associadosà não adesão à anticoagulação oral pode melhorar o entendimento sobre aspectos do tratamento. Cadastro de registro da revisãosistemática (PROSPERO): CRD 42020223555.