Self-reported therapy adherence and predictors for nonadherence in patients who switched from vitamin K antagonists to direct oral anticoagulants

BackgroundMany patients who used vitamin K antagonists (VKAs) for long-term prevention of thromboembolism are now actively switched to a direct oral anticoagulant (DOAC). Strict adherence to a DOAC is crucial for its success. However, therapy adherence and clinical factors that predict nonadherence are currently not well studied among patients who switched from a VKA to a DOAC.MethodsA questionnaire was developed and sent to 2920 former patients of 3 anticoagulation clinics in the Netherlands, who switched from a VKA to a DOAC between January 2016 and December 2017. Questions concerned demographics, treatment persistence, adherence, and the occurrence of bleeding or thromboembolic events on DOACs. To identify predictors for nonadherence, logistic regression models were used to estimate crude and age/sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsA total of 1399 questionnaires (response rate 48%) were used for analysis. DOAC treatment persistence (94%) and adherence (86%) rates were high. Several predictors of nonadherence were identified, including young age (OR, 5.9; 95% CI, 3.6-9.8 for 75 years), low consultation frequency with a specialist (OR, 1.6; 95% CI, 1.1-2.2), a history of minor bleeding on DOACs (OR, 1.9; 95% CI, 1.3-2.8), and a twice-daily dosing regimen (OR, 1.9; 95% CI, 1.3-2.6).ConclusionsSelf-reported treatment persistence and adherence were high in our study population, and several predictors of nonadherence were identified. Factors that can be influenced (low consult frequency with medical specialist, daily dosing regimen) may be used to improve therapy adherence.Thrombosis and Hemostasi

Switching from vitamin K antagonists to direct oral anticoagulants: treatment satisfaction and patient concerns

Background Since direct oral anticoagulants (DOACs) have been introduced for treatment and prevention of thromboembolic diseases, patients on vitamin K antagonists (VKA) have to decide whether to remain on VKA or switch to DOAC. The goal of this study was to evaluate treatment satisfaction, preferences, and concerns among those who already have switched from VKA to DOAC.Methods A questionnaire was sent to 2920 former patients of three anticoagulation clinics in the Netherlands, who switched from VKA to DOAC (2016-2017). Questions concerned demographics, treatment satisfaction, concerns, perspectives on antidotes, and monitoring. To identify predictors for being concerned about adverse events, logistic regression was used to estimate crude- and adjusted (age and sex) odds ratios (OR) and 95% confidence intervals (95% CI).Results One thousand, three hundred ninety-nine questionnaires (response rate 48%) were used for analysis. DOAC treatment satisfaction was high (mean 8.8 of a maximum 10-point score). A quarter of patients expressed concerns about adverse events. Predictors for being concerned were age 75 years, OR 4.1, 95% CI 2.6-6.4), female sex (OR 1.3, 95% CI 1.0-1.6), and high education (OR 1.6, 95% CI 1.2-2.2). Fifty-nine percent of all patients indicated antidote availability as important, 73% would be willing to participate in DOAC monitoring.Conclusions DOAC treatment satisfaction was high. A substantial number of patients expressed concerns about adverse events, especially women, patients aged < 60 years, or highly educated patients. Our findings among patients who already had switched to DOAC may assist in the process of shared decision-making when switching a patient from VKA to DOAC is considered.Thrombosis and Hemostasi

Stability of vitamin K antagonist anticoagulation after COVID-19 diagnosis

Background: Coagulopathy has been reported in severely ill patients with coronavirus disease 2019 (COVID-19). It is unclear whether outpatients with COVID-19 who are treated with vitamin K antagonists (VKAs) have unstable anticoagulation.Objective: To assess the stability of VKA therapy in patients with COVID-19 through a case-crossover study.Methods: Between February and July 2020, we included patients who tested positive for COVID-19 from two anticoagulant clinics in the Netherlands. We collected international normalized ratios (INRs) determined between 26 weeks before infection and 12 weeks after. Time in therapeutic range (TTR) and the variance growth rate ( VGR) were calculated within patients.Results: Fifty-one patients with COVID-19 (mean age, 84 years) were included, of whom 15 (29%) were men. Mean TTR in the 26 weeks before COVID-19 was 80% (95% confidence interval [CI], 75-85) compared to 59% (95% CI, 51-68) in the 6 weeks after infection. Mean TTR difference was-23% (95% CI, -32 to -14) with a time above therapeutic range of 38% (95% CI, 30-47) in the 6 weeks after infection. The TTR rose again to 79% (95% CI, 69-89) between 6 and 12 weeks after infection. Also, VGR increased, with a mean increase of 4.8 (95% CI, 2.1-7.5) in the 6 weeks after infection. In the 26 weeks before infection, we registered 19 of 641 (3%) of INR >= 5.0 compared with 35 of 247 (14%) in the 6 weeks after (risk ratio, 4.4; 95% CI, 2.7-7.3).Conclusions: COVID-19 is associated with a strong decrease in TTR and in therapeutic stability in patients taking VKAs. Additional monitoring in these patients is advised to maximize therapeutic stability.Clinical epidemiolog

Inter- and intra-individual concentrations of direct oral anticoagulants: the KIDOAC study

Background Direct oral anticoagulants (DOACs) do not require concentration monitoring. However, whether DOAC concentrations are stable and their variation between and within patients is not well studied. Methods Patients on vitamin K antagonists (VKA) who switched to rivaroxaban, apixaban, or dabigatran were included between 2018 and 2020. Blood was drawn at DOAC trough and peak concentrations at week 0, 2, and 8. Plasma drug concentrations were determined by anti-factor Xa concentrations (rivaroxaban, apixaban) or diluted thrombin time (dabigatran). Inter- and intra-individual variability was assessed by calculating the coefficient of variation (CV). Linear regression models were employed to evaluate associations between DOAC trough concentrations and previous VKA dosage, creatinine clearance, and body mass index (BMI). Results One hundred fifty-two patients were included, of whom 96 (63%) were male and with a mean age of 73.9 +/- 8.4 years. For the inter-individual variability, the CV ranged between 48% and 81% for trough values and between 25% and 69% for peak values among patients using the recommended DOAC dose. Intra-individual variability was substantially lower, as here the CV ranged between 18% and 33% for trough values and between 15% and 29% for peak values among patients using the recommended DOAC dose. Previous VKA dosage and creatinine clearance were inversely associated with DOAC trough concentrations. No association was found between BMI and DOAC trough concentrations. Conclusion Inter-individual variability of DOAC concentrations was higher than intra-individual variability. Lower previous VKA dosage and creatinine clearance were associated with higher DOAC trough concentrations. These findings support further study into an optimal target range, in which the risks of both bleeding and thrombosis are minimal

Switching from vitamin K antagonists to direct oral anticoagulants in non-valvular atrial fibrillation patients: Does low time in therapeutic range affect persistence?

Background Non-valvular atrial fibrillation (NVAF) patients are advised to switch from a vitamin K antagonist (VKA) to direct oral anticoagulant (DOAC) when time in therapeutic range (TTR) is low. Objective To examine if pre-switch TTR determines persistence patterns in NVAF patients who are switched from a VKA to DOAC. Patients/Methods Adult NVAF patients from three Dutch anticoagulation clinics who were newly switched from a VKA to DOAC between July 1, 2013 and September 30, 2018 were stratified by pre-switch TTR levels. DOAC prescription records were examined to determine persistence patterns according to a 100-day prescription gap. Cumulative incidences of non-persistence to DOAC were estimated using the cumulative incidence competing risk method. The association of pre-switch TTR levels with DOAC non-persistence was evaluated by Cox regression models. Results A total of 3696 NVAF patients were included, of whom 690 (18.7%) had a pre-switch TTR 45%. In a multivariable model, a pre-switch TTR <= 45% was associated with a higher risk of non-persistence to DOAC (adjusted hazard ratio 1.55, 95% CI 1.22-1.97). Results were similar when using other cut-off points (60% or 70%) to define a low TTR. Conclusion NVAF patients switching from VKA to DOAC due to a low pre-switch TTR saw a worse persistence pattern to DOAC after the switch compared to patients with a high pre-switch TTR.Clinical epidemiolog

The Immediate Effect of COVID-19 Vaccination on Anticoagulation Control in Patients Using Vitamin K Antagonists

Background In January 2021, the Dutch vaccination program against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications.Aims This article investigates whether the BNT162b2 vaccine affects anticoagulation control in outpatients using vitamin K antagonists (VKAs).Methods A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. International normalized ratio (INR) results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination.Results A total of 3,148 outpatient VKA users were included, with amean age (standard deviation) of 86.7 (8.7) years, of whom 43.8% weremale, 67.0% used acenocoumarol, and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic (odds ratio [OR] = 1.34 [95% confidence interval [CI] 1.08-1.67]) and subtherapeutic levels (OR = 1.40 [95% CI 1.08-1.83]) after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination (OR = 2.29 [95% CI 1.22-4.28]) and 3.3 times higher after second vaccination (OR = 3.25 [95% CI 1.06-9.97]).Conclusion BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with VKAs, so it is advisable to monitor the INR shortly after vaccination, even in stable patients.[GRAPHICS].Clinical epidemiolog