Effect of Previous INR Control during VKA Therapy on Subsequent DOAC Adherence and Persistence, in Patients Switched from VKA to DOAC.

INTRODUCTION: Current guideline suggests a switch from vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) in patients with low time in therapeutic range (TTR < 70%). Poor international normalized ratio (INR) control may be the result of poor compliance, and might therefore be associated with subsequent DOAC intake. Therefore, this study evaluates the effect of previous TTR and other measures of INR control on DOAC nonadherence and nonpersistence, in patients who switched from VKA to DOAC. METHODS: A total of 437 patients who switched from VKA to DOAC between 2012 and 2019 were included using data from Certe Thrombosis Service, IADB.nl pharmacy community database University Groningen, and Statistics Netherlands. DOAC prescriptions were used to determine nonadherence and nonpersistence. INR control (i.e., TTR, time under therapeutic range [TUR], and INR variability) was assessed during the last 180 days of VKA use. Multivariable regression models were applied to determine the association between INR control and DOAC nonpersistence/nonadherence. RESULTS: On VKA, 67.7% of the patients had a TTR below 70%. DOAC nonpersistence was 39.8% (95% confidence interval [CI]: 33.4-45.5%) during a median follow-up of 34.4 months (interquartile range: 19.1-49.2). Approximately 80% of persistent patients were DOAC-adherent. Low TTR was not associated with DOAC nonpersistence (hazard ratio: 1.14, 95% CI: 0.69-1.87) and DOAC nonadherence (odds ratio: 1.38, 95% CI: 0.67-2.84), nor were TUR and INR variability. CONCLUSION: Previous INR control during VKA therapy is not associated with subsequent DOAC nonadherence and nonpersistence. This study suggests that INR control on VKA cannot, and therefore should not, be used for predicting DOAC adherence or persistence.

Anticoagulants for thrombosis prophylaxis in acutely ill patients admitted to hospital: systematic review and network meta-analysis.

OBJECTIVE: To assess the benefits and harms of different types and doses of anticoagulant drugs for the prevention of venous thromboembolism in patients who are acutely ill and admitted to hospital. DESIGN: Systematic review and network meta-analysis. DATA SOURCES: Cochrane CENTRAL, PubMed/Medline, Embase, Web of Science, clinical trial registries, and national health authority databases. The search was last updated on 16 November 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Published and unpublished randomised controlled trials that evaluated low or intermediate dose low-molecular-weight heparin, low or intermediate dose unfractionated heparin, direct oral anticoagulants, pentasaccharides, placebo, or no intervention for the prevention of venous thromboembolism in acutely ill adult patients in hospital. MAIN OUTCOME MEASURES: Random effects, bayesian network meta-analyses used four co-primary outcomes: all cause mortality, symptomatic venous thromboembolism, major bleeding, and serious adverse events at or closest timing to 90 days. Risk of bias was also assessed using the Cochrane risk-of-bias 2.0 tool. The quality of evidence was graded using the Confidence in Network Meta-Analysis framework. RESULTS: 44 randomised controlled trials that randomly assigned 90 095 participants were included in the main analysis. Evidence of low to moderate quality suggested none of the interventions reduced all cause mortality compared with placebo. Pentasaccharides (odds ratio 0.32, 95% credible interval 0.08 to 1.07), intermediate dose low-molecular-weight heparin (0.66, 0.46 to 0.93), direct oral anticoagulants (0.68, 0.33 to 1.34), and intermediate dose unfractionated heparin (0.71, 0.43 to 1.19) were most likely to reduce symptomatic venous thromboembolism (very low to low quality evidence). Intermediate dose unfractionated heparin (2.63, 1.00 to 6.21) and direct oral anticoagulants (2.31, 0.82 to 6.47) were most likely to increase major bleeding (low to moderate quality evidence). No conclusive differences were noted between interventions regarding serious adverse events (very low to low quality evidence). When compared with no intervention instead of placebo, all active interventions did more favourably with regard to risk of venous thromboembolism and mortality, and less favourably with regard to risk of major bleeding. The results were robust in prespecified sensitivity and subgroup analyses. CONCLUSIONS: Low-molecular-weight heparin in an intermediate dose appears to confer the best balance of benefits and harms for prevention of venous thromboembolism. Unfractionated heparin, in particular the intermediate dose, and direct oral anticoagulants had the least favourable profile. A systematic discrepancy was noted in intervention effects that depended on whether placebo or no intervention was the reference treatment. Main limitations of this study include the quality of the evidence, which was generally low to moderate due to imprecision and within-study bias, and statistical inconsistency, which was addressed post hoc. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020173088.

Convenience and satisfaction in direct oral anticoagulant-treated patients with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) are the preferred anticoagulants for thromboprophylaxis in atrial fibrillation. We aimed to identify determinants of quality of life related to DOAC treatment to optimize DOAC treatment convenience and satisfaction. METHODS: We conducted a cross-sectional study in DOAC users. DOAC treatment-related convenience and satisfaction were measured by Perception of Anticoagulant Treatment Questionnaire. Higher scores are more favorable (range, 0-100). Patient-reported outcome measures and drug- and organization-related factors were collected. Multiple regression analyses were used to evaluate the association between these factors (ie, exposure variables) and DOAC treatment-related convenience and treatment satisfaction (ie, outcome variables). RESULTS: Of 1598 patients invited, 1035 responded, and 962 were included. The median convenience score was 98.1 (94.2-100.0), mean satisfaction score 66.5± 14.9. Twenty-four percent felt not well informed at the start of DOAC; 6.9% did not know who to turn to with questions. Multiple regression analyses showed that lacking sense of security, the predefined composite of receiving insufficient information at start of DOAC and/or not knowing who to turn to with questions was associated with lower convenience (regression coefficient, -1.29; 95% confidence interval [CI], -2.16 to -0.41). Bleeding, gastrointestinal complaints, and lower medication adherence were also associated with lower convenience. Missing sense of security (regression coefficient -6.59; 95% CI, -8.94 to -4.24) and bleeding without consultation were associated with lower treatment satisfaction. CONCLUSIONS: Accessible interventions to improve DOAC care could be providing more instruction at treatment initiation and ensuring that patients know who to contact in case of problems.