Objective Patients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with... Show moreObjective Patients with cancer are at increased bleeding risk, and anticoagulants increase this risk even more. Yet, validated bleeding risk models for prediction of bleeding risk in patients with cancer are lacking. The aim of this study is to predict bleeding risk in anticoagulated patients with cancer.Methods We performed a study using the routine healthcare database of the Julius General Practitioners’ Network. Five bleeding risk models were selected for external validation. Patients with a new cancer episode during anticoagulant treatment or those initiating anticoagulation during active cancer were included. The outcome was the composite of major bleeding and clinically relevant non-major (CRNM) bleeding. Next, we internally validated an updated bleeding risk model accounting for the competing risk of death.Results The validation cohort consisted of 1304 patients with cancer, mean age 74.0±10.9 years, 52.2% males. In total 215 (16.5%) patients developed a first major or CRNM bleeding during a mean follow-up of 1.5 years (incidence rate; 11.0 per 100 person-years (95% CI 9.6 to 12.5)). The c-statistics of all selected bleeding risk models were low, around 0.56. Internal validation of an updated model accounting for death as competing risk showed a slightly improved c-statistic of 0.61 (95% CI 0.54 to 0.70). On updating, only age and a history of bleeding appeared to contribute to the prediction of bleeding risk.Conclusions Existing bleeding risk models cannot accurately differentiate bleeding risk between patients. Future studies may use our updated model as a starting point for further development of bleeding risk models in patients with cancer. Show less
BackgroundCancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF).ObjectivesWe aimed to describe current anticoagulant practice in patients with AF... Show moreBackgroundCancer is suggested to confer thromboembolic and bleeding risk in patients with atrial fibrillation (AF).ObjectivesWe aimed to describe current anticoagulant practice in patients with AF and active cancer, present incidences of thromboembolic and bleeding complications, and evaluate the association between cancer type or anticoagulant management strategy with AF-related complications.MethodsThis retrospective study identified patients with AF and active cancer in 2 hospitals between January 1, 2012, and December 31, 2017. Follow-up lasted for 2 years. Data on cancer and anticoagulant treatment were collected. The outcomes of interest included ischemic stroke or transient ischemic attack (TIA) and clinically relevant nonmajor bleeding (CRNMB/MB). Incidence rates (IRs) per 100 patient-years and subdistribution hazard ratios (SHRs) with corresponding 95% Cis were estimated.ResultsWe identified 878 patients with AF who developed cancer (cohort 1) and 335 patients with cancer who developed AF (cohort 2). IRs for ischemic stroke/TIA and MB/CRNMB were 3.9 (2.8-5.3) and 15.7 (13.3-18.5) for cohort 1 and 4.0 (2.2-6.7) and 16.7 (12.6-21.7) for cohort 2. 14.2% (cohort 1) and 19.1% (cohort 2) of patients with a CHA2DS2-VASc score of ≥2 did not receive anticoagulant treatment. Withholding anticoagulants was associated with thromboembolic complications (SHR: 5.1 [3.20-8.0]). In nonanticoagulated patients with a CHA2DS2-VASc score of <2, IRs for stroke/TIA were 4.5 (0.75-15.0; cohort 1) and 16.0 (5.1-38.7; cohort 2).ConclusionPatients with AF and active cancer experience high rates of thromboembolic and bleeding complications, underlying the complexity of anticoagulant management in these patients. Our data suggest that the presence of cancer is an important factor in determining the indication for anticoagulants in patients with a low CHA2DS2-VASc score. Show less
Zielinski, G.D.; Rein, N. van; Teichert, M.; Klok, F.A.; Rosendaal, F.R.; Meer, F.J.M. van der; ... ; Lijfering, W.M. 2021
Background Adherence to direct oral anticoagulants (DOACs) in patients with atrial fibrillation in every day practice may be less than in clinical trials.Aims To assess adherence to DOACs in atrial... Show moreBackground Adherence to direct oral anticoagulants (DOACs) in patients with atrial fibrillation in every day practice may be less than in clinical trials.Aims To assess adherence to DOACs in atrial fibrillation patients in every day practice and identify predictors for non-adherence.Methods Individual linked dispensing data of atrial fibrillation patients who used DOACs were obtained from the Foundation for Pharmaceutical Statistics covering the Netherlands between 2012 and 2016. One year adherence to DOAC was calculated for initial DOAC as proportion of days covered (PDC) >= 80% and the association between clinical variables and adherence was assessed using logistic regression. In addition, we measured non-persistence, that is, patients who completely stopped their initial DOAC within 1 year follow-up.Results A total of 4797 apixaban-, 20 454 rivaroxaban- and 18 477 dabigatran users were included. The mean age was 69 years (n = 43 910), which was similar for the DOAC types. The overall proportion of patients with PDC >= 80% was 76%, which was highest for apixaban- (87%), followed by dabigatran- (80%) and rivaroxaban (69%) users. Multivariable analyses revealed that age <= 60 years, no concomitant drug use were predictors for non-adherence. Of atrial fibrillation patients who continued treatment, 97% had a PDC >= 80%, compared with only 56% for those who discontinued their DOAC treatment within 1 year.Conclusions Non-adherence to DOACs was associated with age <= 60 years and no concomitant drugs use. Non-adherence was higher in patients who later discontinued DOAC treatment. Results of our study support research into interventions to improve adherence. Show less
ObjectivesCurrent international guidelines advocate the application of bleeding risk scores only to identify modifiable risk factors, but not to withhold treatment in patients at high risk of... Show moreObjectivesCurrent international guidelines advocate the application of bleeding risk scores only to identify modifiable risk factors, but not to withhold treatment in patients at high risk of bleeding. VTE-BLEED (ActiVe cancer, male with uncontrolled hyperTension, anaEmia, history of BLeeding, agE and rEnal Dysfunction) is a simple bleeding risk score that predicts major bleeding (MB) in patients with venous thromboembolism, but has never been evaluated in patients with atrial fibrillation (AF). We sought to evaluate VTE-BLEED in patients with AF included in the Randomised Evaluation of Long-term anticoagulant therapY (RE-LY) trial, to assess whether score classes (high vs low bleeding risk) interact with the tested dabigatran doses (150 vs 110 mg twice daily), and to investigate whether dose reductions based on this interaction might help to lower the incidence of the composite outcome MB, stroke/systemic embolism or death.MethodsThe score was calculated in the safety population of RE-LY (n=18 040) and recalibrated for AF (AF-adapted VTE-BLEED or AF-BLEED). HRs were calculated to evaluate the score's predictive accuracy for MB. The risk ratios (RRs) for the composite outcome comparing dabigatran 150 and 110 mg twice daily were calculated for the high-risk group.ResultsAF-BLEED classified 3534 patients (19.6%) at high bleeding risk, characterised by a 2.9-fold to 3.4-fold higher risk of bleeding than low bleeding risk patients, across the treatment arms. High bleeding risk patients randomised to 110 mg twice daily had a lower incidence of the composite outcome than those randomised to 150 mg twice daily, for an RR of 0.52 (95% CI 0.35 to 0.78). Compared with the label criteria for dose reduction, AF-BLEED identified an additional 11% of patients who might have benefited from dose reduction.ConclusionsAF-BLEED identified patients with AF at high risk of bleeding. Our findings raise the hypothesis that dabigatran 110 mg twice daily might be considered in patients classified as high risk according to the AF-BLEED score. This study provides a basis for future studies to explore safe dose reductions of direct oral anticoagulants in selected patient groups based on bleeding scores. Show less
Zielinski, G.D.; Rein, N. van; Teichert, M.; Klok, F.A.; Rosendaal, F.R.; Meer, F.J.M. van der; ... ; Lijfering, W.M. 2019
Background In contrast to vitamin K antagonists (VKA), direct oral anticoagulants (DOAC's) are not strictly monitored and dose titrated by anticoagulation clinics in the Netherlands. This may... Show moreBackground In contrast to vitamin K antagonists (VKA), direct oral anticoagulants (DOAC's) are not strictly monitored and dose titrated by anticoagulation clinics in the Netherlands. This may affect drug persistence of atrial fibrillation (AF) patients, whom often require lifelong treatment. Objectives To assess persistence of DOACs and of VKAs in patients with AF. Methods Dispensing data from the Dutch Foundation of Pharmaceutical Statistics were used to monitor persistence of AF patients to DOAC from 1 January 2012-1 April 2016. In addition, we estimated the persistence of AF patients to VKA between 1 January 2004 and 1 January 2012 in data from the Anticoagulation Clinic Leiden. Non-persistence was defined as the cumulative incidence of patients who completely stopped DOAC, switched to another oral anticoagulant or stopped their VKA. Results DOAC users (n = 77 333) were younger than VKA users (n = 10 079; 70 vs 73 years). Non-Persistence to DOAC (ie stopping with any oral anticoagulant) was 34% at 1 and 64% at 4 years, compared to 22% at one and 36% at 4 years for VKA. Approximately a Twenty-five percent of those who had stopped their initial DOAC switched to another anticoagulant (VKA or another DOAC). Multivariable analyses revealed that young age, female sex, no concomitant drug use and non-adherence were predictors for non-persistence of DOAC. Conclusions Persistence to DOAC was low and in line with other observational studies, and higher for VKA. Our results show a clear correlation between age <60 years and worse persistence, as well as with female and non-adherence to DOAC. Show less
Wall, S.J. van der; Lopes, R.D.; Aisenberg, J.; Reilly, P.; Ryn, J. van; Glund, S.; ... ; Huisman, M.V. 2019
