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Prescribing trends of oral anticoagulants in England over the last decade: a focus on new and old drugs and adverse events reporting.

ABSTRACT: Direct-acting oral anticoagulants (DOACs) are replacing conventional VKA (vitamin K antagonist, i.e., warfarin) for various indications where a therapeutic anticoagulant effect is desired. We evaluated the prescribing patterns of the DOACs and warfarin, cost implications of the increasing DOACs prescribing, and deduce the reporting of serious and fatal events, during 2009-2019 in primary care England. Prescriptions and fatal or serious adverse events reporting data, between 2009 and 2019 were analysed, using linear regression to examine the trends in prescriptions, costs, and serious and fatal events reporting. We also compared the prescribing trends of four direct-acting oral anticoagulants and warfarin, normalised to per 1000 clinical commissioning group (CCG) patient population for the year 2019 to better understand the regional differences in DOACs prescribing. The overall use of any DOACs (as a proportion of total anticoagulants) increased from 16% in 2015 to 62% in 2019 with an average increase of 87% (95% CI 83.1, 90.5) per year. The reporting of serious and fatal events associated with DOACs decreased by 6% (95% CI 12.5, - 0.1) per year. Apixaban is by far the most prescribed with an average drug cost increasing to 156% (95% CI 140, 172) per year. In England, the lowest anticoagulant prescribing region was Greater London whereas the highest prescribing regions were Yorkshire and Humber for DOACs and the East Midlands for warfarin. Interestingly, Lancashire, Merseyside, and Cheshire showed a higher usage for warfarin over DOACs. The differing prescription patterns could be a result of changes in national guidelines and increasing population. Nevertheless, DOACs appear to make an increasing contribution to total anticoagulant prescription items and costs.

SUBMITTER: Afzal S

PROVIDER: S-EPMC7933373 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceContemporary national clinical practice guidelines recommend direct-acting oral anticoagulants (DOACs) as the first-line anticoagulant strategy over warfarin for most indications, especially among older individuals with an elevated bleeding risk.ObjectiveTo evaluate anticoagulant prescribing and DOAC uptake by US clinicians in the Medicare population.Design, setting, and participantsThis retrospective cohort study included all US clinicians with more than 10 Medicare oral anticoagulant prescription claims, who were included in the national Medicare Provider Utilization and Payment Data (2013-2018). Data analyses were conducted between October 2020 and October 2021.ExposuresDOAC prescription in 2013.Main outcomes and measuresClinicians were categorized based on 2013 prescribing as solely prescribing warfarin, DOAC, or both, and their temporal trajectories of proportionate DOAC use were examined.ResultsThe analysis included 325 666 unique clinicians with more than 10 oral anticoagulant prescriptions between 2013 and 2018 (26 620 [8.2%] cardiologists, 85 563 [26.3%] internal medicine physicians, 84 369 [25.9%] family medicine physicians, and 81 161 [24.9%] advanced practice clinicians, including nurse practitioners and physician assistants). In 2013, among 91 837 prescribers, 54 501 (59.3%) prescribed only warfarin, 1918 (2.1%) prescribed only a DOAC, and 35 418 (38.6%) prescribed both. During the study period, the number of clinicians prescribing DOACs increased, but 19% continued to prescribe only warfarin in 2018. While 359 cardiologists prescribing anticoagulants (1.6%) were warfarin-only prescribers, 10 414 (20.0%) and 6296 (12.6%) of family and internal medicine physicians also prescribed only warfarin, respectively. Clinicians prescribing only warfarin in 2013 had lower proportionate DOAC use throughout the study compared with 2013 DOAC prescribers, which represents a median (IQR) of 41.9% (20.3%-61.9%) of their anticoagulant prescriptions in 2018 vs 67.0% (49.9%-82.8%) for DOAC prescribers.Conclusions and relevanceDespite the increase in DOAC use among Medicare beneficiaries, many clinicians in this study continued to use warfarin as their predominant or only anticoagulant instead of DOACs. There is a need to address barriers to the uptake of these medications to realize their potential benefits for patients.

Project description:The excitation-contraction coupling (ECC) in skeletal muscle refers to the Ca2+-mediated link between the membrane excitation and the mechanical contraction. The initiation and propagation of an action potential through the membranous system of the sarcolemma and the tubular network lead to the activation of the Ca2+-release units (CRU): tightly coupled dihydropyridine and ryanodine (RyR) receptors. The RyR gating allows a rapid, massive, and highly regulated release of Ca2+ from the sarcoplasmic reticulum (SR). The release from triadic places generates a sarcomeric gradient of Ca2+ concentrations ([Ca2+]) depending on the distance of a subcellular region from the CRU. Upon release, the diffusing Ca2+ has multiple fates: binds to troponin C thus activating the contractile machinery, binds to classical sarcoplasmic Ca2+ buffers such as parvalbumin, adenosine triphosphate and, experimentally, fluorescent dyes, enters the mitochondria and the SR, or is recycled through the Na+/Ca2+ exchanger and store-operated Ca2+ entry (SOCE) mechanisms. To commemorate the 7th decade after being coined, we comprehensively and critically reviewed "old", historical landmarks and well-established concepts, and blended them with recent advances to have a complete, quantitative-focused landscape of the ECC. We discuss the: 1) elucidation of the CRU structures at near-atomic resolution and its implications for functional coupling; 2) reliable quantification of peak sarcoplasmic [Ca2+] using fast, low affinity Ca2+ dyes and the relative contributions of the Ca2+-binding mechanisms to the whole concert of Ca2+ fluxes inside the fibre; 3) articulation of this novel quantitative information with the unveiled structural details of the molecular machinery involved in mitochondrial Ca2+ handing to understand how and how much Ca2+ enters the mitochondria; 4) presence of the SOCE machinery and its different modes of activation, which awaits understanding of its magnitude and relevance in situ; 5) pharmacology of the ECC, and 6) emerging topics such as the use and potential applications of super-resolution and induced pluripotent stem cells (iPSC) in ECC. Blending the old with the new works better!

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Prescribing trends of oral anticoagulants in England over the last decade: a focus on new and old drugs and adverse events reporting.

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