The Number of Concomitant Drugs and the Safety of Direct Oral Anticoagulants in Routine Care Patients with Atrial Fibrillation

Dries, Carline J van den; Doorn, Sander van; Souverein, Patrick C.; Pajouheshnia, Romin; Moons, Karel G.M.; Hoes, Arno W.; Geersing, Geert‐Jan; Ham, Hendrika A. van den

doi:10.1055/s-0040-1721499

Cited by 12 publications

(10 citation statements)

References 30 publications

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“…We used a maximum of 3 years of follow-up data, after which the disease episode of active cancer was considered dissolved. Because the theoretical end date of a drug prescription often does not correspond with the actual end of anticoagulant treatment (due to, eg, stockpiling or medication non-compliance), we used a ‘grace’ period of 14 days to extend the anticoagulant treatment period after the date of the last prescription to adjust for this, an approach often applied in the field of bleeding risk analyses 16. ICPC codes and ATC codes used for predictors and bleeding outcomes are listed in online supplemental file 2.…”

Section: Methodsmentioning

confidence: 99%

External validation and updating of prediction models of bleeding risk in patients with cancer receiving anticoagulants

et al. 2023

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ObjectivePatients 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.MethodsWe 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.ResultsThe 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.ConclusionsExisting 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.

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Section: Methodsmentioning

confidence: 99%

External validation and updating of prediction models of bleeding risk in patients with cancer receiving anticoagulants

et al. 2023

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“…[20][21][22] Finally, a total of 12 studies were included in our meta-analysis. [8][9][10]15,[23][24][25][26][27][28][29][30]…”

Section: Resultsmentioning

confidence: 99%

“…The baseline characteristics of the included studies are illustrated in ►Table 1. Among the nine included observational studies, three were from the United Kingdom, 29 Germany, 8 and Japan, 30 and the other six were derived from nationwide or health insurance claims databases in the United States. 15,[23][24][25][26][27] Of the three included post-hoc analyses of RCTs, 9,10,28 all were multicenter large-scale randomized clinical trials.…”

Section: Study Characteristics and Qualitymentioning

confidence: 99%

Effect of Oral Anticoagulants in Atrial Fibrillation Patients with Polypharmacy: A Meta-analysis

Zheng

Liu

et al. 2023

Thromb Haemost

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Background The aim of the present meta-analysis was to evaluate the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients with polypharmacy. Methods and Results Randomized controlled trials or observational studies reporting the data of NOACs versus VKAs among AF patients with polypharmacy were included. The search was performed in the PubMed and Embase databases up to November 2022. A total of 12 studies involving 767,544 AF patients were included. For the primary outcomes, the use of NOACs compared with VKAs was significantly associated with a reduced risk of stroke or systemic embolism in AF patients with moderate polypharmacy (hazard ratio [HR]: 0.77 [95% confidence interval [CI]: 0.69–0.86]) and severe polypharmacy (HR: 0.76 [95% CI: 0.69–0.82]), but there was no significant difference in major bleeding (moderate polypharmacy: HR: 0.87 [95% CI: 0.74–1.01]; severe polypharmacy: HR: 0.91 [95% CI: 0.79–1.06]) between the two groups. In secondary outcomes, there were no differences in the rates of ischemic stroke, all-cause death, and gastrointestinal bleeding between the NOAC- and VKA- users, but NOAC users had a reduced risk of any bleeding compared with VKA- users. Compared with VKAs, the risk of intracranial hemorrhage was reduced in NOAC- users with moderate polypharmacy but not severe polypharmacy. Conclusion In patients with AF and polypharmacy, NOACs showed advantages over VKAs in stroke or systemic embolism and any bleeding, and were comparable to VKAs for major bleeding, ischemic stroke, all-cause death, intracranial hemorrhage, and gastrointestinal bleeding.

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“…Therefore, similar to our previous study using the CPRD database, for all analyses, we decided post hoc to reclassify the first 30 days after apparent discontinuation to exposure to the last NOAC used (ie, a “last measurement carried forward” approach). 26 …”

Section: Methodsmentioning

confidence: 99%

Safety of off‐label dose reduction of non‐vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

Dries

Pajouheshnia

Ham

et al. 2022

Brit J Clinical Pharma

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Aim To investigate the effects of off‐label non‐vitamin K oral anticoagulant (NOAC) dose reduction compared with on‐label standard dosing in atrial fibrillation (AF) patients in routine care. Methods Population‐based cohort study using data from the United Kingdom Clinical Practice Research Datalink, comparing adults with non‐valvular AF receiving an off‐label reduced NOAC dose to patients receiving an on‐label standard dose. Outcomes were ischaemic stroke, major/non‐major bleeding and mortality. Inverse probability of treatment weighting and inverse probability of censoring weighting on the propensity score were applied to adjust for confounding and informative censoring. Results Off‐label dose reduction occurred in 2466 patients (8.0%), compared with 18 108 (58.5%) on‐label standard‐dose users. Median age was 80 years (interquartile range [IQR] 73.0‐86.0) versus 72 years (IQR 66‐78), respectively. Incidence rates were higher in the off‐label dose reduction group compared to the on‐label standard dose group, for ischaemic stroke (0.94 vs 0.70 per 100 person years), major bleeding (1.48 vs 0.83), non‐major bleeding (6.78 vs 6.16) and mortality (10.12 vs 3.72). Adjusted analyses resulted in a hazard ratio of 0.95 (95% confidence interval [CI] 0.57‐1.60) for ischaemic stroke, 0.88 (95% CI 0.57‐1.35) for major bleeding, 0.81 (95% CI 0.67‐0.98) for non‐major bleeding and 1.34 (95% CI 1.12‐1.61) for mortality. Conclusion In this large population‐based study, the hazards for ischaemic stroke and major bleeding were low, and similar in AF patients receiving an off‐label reduced NOAC dose compared with on‐label standard dose users, while non‐major bleeding risk appeared to be lower and mortality risk higher. Caution towards prescribing an off‐label reduced NOAC dose is therefore required.

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The Number of Concomitant Drugs and the Safety of Direct Oral Anticoagulants in Routine Care Patients with Atrial Fibrillation

Cited by 12 publications

References 30 publications

External validation and updating of prediction models of bleeding risk in patients with cancer receiving anticoagulants

External validation and updating of prediction models of bleeding risk in patients with cancer receiving anticoagulants

Effect of Oral Anticoagulants in Atrial Fibrillation Patients with Polypharmacy: A Meta-analysis

Safety of off‐label dose reduction of non‐vitamin K antagonist oral anticoagulants in patients with atrial fibrillation

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