Safety of off-label dose reduction of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation
© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:89 |
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| Enthalten in: |
British journal of clinical pharmacology - 89(2023), 2 vom: 29. Feb., Seite 751-761 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
van den Dries, Carline J [VerfasserIn] |
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| Links: |
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| Themen: |
Anticoagulants |
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| Anmerkungen: |
Date Completed 17.01.2023 Date Revised 15.04.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/bcp.15534 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM346188946 |
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| 100 | 1 | |a van den Dries, Carline J |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Safety of off-label dose reduction of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 17.01.2023 | ||
| 500 | |a Date Revised 15.04.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a anticoagulation | |
| 650 | 4 | |a atrial fibrillation | |
| 650 | 4 | |a non-vitamin K antagonist oral anticoagulants | |
| 650 | 4 | |a off-label dose reduction | |
| 650 | 7 | |a Anticoagulants |2 NLM | |
| 700 | 1 | |a Pajouheshnia, Romin |e verfasserin |4 aut | |
| 700 | 1 | |a van den Ham, Hendrika A |e verfasserin |4 aut | |
| 700 | 1 | |a Souverein, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Moons, Karel G M |e verfasserin |4 aut | |
| 700 | 1 | |a Hoes, Arno W |e verfasserin |4 aut | |
| 700 | 1 | |a Geersing, Geert-Jan |e verfasserin |4 aut | |
| 700 | 1 | |a van Doorn, Sander |e verfasserin |4 aut | |
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