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      Moving Towards Ideal and Appropriate Models of Anticoagulation Management Service

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          Abstract

          It is now known that thrombotic disorders such as venous thromboembolism, ischemic stroke, and myocardial infarction contribute significantly to global morbidity and mortality. Anticoagulation service must respond to this new development. Warfarin has continued to provide the backbone for anticoagulation service for decades but with considerable drawbacks. The introduction of nonVitamin K oral anticoagulants (NOACs) has created new challenges. This article seeks to discuss how the establishment of appropriate models of anticoagulation could contain the draw backs of the old anticoagulants and improve on the compliance, availability, affordability, and accessibility of newer anticoagulants. Successful anticoagulation has always been defined by a scientific balancing of the risk of thrombosis and the complication of hemorrhage. To be able to maintain such optimal anticoagulation requires rational drug prescription (physician factor), institutelization of monitoring of therapy (anticoagulation clinic factor) as well as active participation of patients receiving therapy (patient factor). New models of service can be created out of this triad in a bid to replace the old routine medical care model. New models of anticoagulation service should include appropriately trained professionals such as Physicians, Pharmacists, Clinical Pharmacologists, Nurses, and Laboratory Scientists who are knowledgeable in diagnostic, management, and monitoring of anticoagulation. The different models of anticoagulation service discussed in this article clearly demonstrate the need for restructuring of this life saving service particularly in the era of NOAC. Newer models of care that should provide safe, efficacious, and cost-effective services are needed.

          Résumé

          On sait maintenant que les troubles thrombotiques tels que la thromboembolie veineuse, l’accident vasculaire cérébral ischémique et l’infarctus du myocarde contribuent de manière significative à la morbidité et à la mortalité mondiales. Le service d’anticoagulation doit répondre à ce nouveau développement. L’introduction d’anticoagulants oraux sans vitamine K (NOAC) a créé de nouveaux défis. Cet article cherche à discuter de la manière dont la mise en place de modèles appropriés d’anticoagulation pourrait contenir les inconvénients des anciens anticoagulants et améliorer la conformité, la disponibilité, l’abordabilité et l’accessibilité des anticoagulants plus récents. Une anticoagulation réussie a toujours été définie par un équilibre scientifique du risque de thrombose et de la complication hémorragique. Pour pouvoir maintenir une telle anticoagulation optimale, il faut une prescription rationnelle des médicaments (facteur médecin), une institutionnalisation de la surveillance du traitement (facteur clinique d’anticoagulation) ainsi qu’une participation active des patients recevant un traitement (facteur patient). De nouveaux modèles de service peuvent être créés à partir de cette triade dans le but de remplacer l’ancien modèle de soins médicaux de routine. Les nouveaux modèles de service d’anticoagulation devraient inclure des professionnels dûment formés tels que des médecins, des pharmaciens, des pharmacologues cliniciens, des infirmières et des scientifiques de laboratoire qui sont bien informés en diagnostic, en gestion et en surveillance de l’anticoagulation. Les différents modèles de service d’anticoagulation abordés dans cet article démontrent clairement la nécessité de restructurer ce service de sauvetage, en particulier à l’ère du NOAC. De nouveaux modèles de soins qui devraient fournir des services sûrs, efficaces et rentables sont nécessaires.

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          Most cited references63

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          Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.

          Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Rivaroxaban versus warfarin in nonvalvular atrial fibrillation.

            The use of warfarin reduces the rate of ischemic stroke in patients with atrial fibrillation but requires frequent monitoring and dose adjustment. Rivaroxaban, an oral factor Xa inhibitor, may provide more consistent and predictable anticoagulation than warfarin. In a double-blind trial, we randomly assigned 14,264 patients with nonvalvular atrial fibrillation who were at increased risk for stroke to receive either rivaroxaban (at a daily dose of 20 mg) or dose-adjusted warfarin. The per-protocol, as-treated primary analysis was designed to determine whether rivaroxaban was noninferior to warfarin for the primary end point of stroke or systemic embolism. In the primary analysis, the primary end point occurred in 188 patients in the rivaroxaban group (1.7% per year) and in 241 in the warfarin group (2.2% per year) (hazard ratio in the rivaroxaban group, 0.79; 95% confidence interval [CI], 0.66 to 0.96; P<0.001 for noninferiority). In the intention-to-treat analysis, the primary end point occurred in 269 patients in the rivaroxaban group (2.1% per year) and in 306 patients in the warfarin group (2.4% per year) (hazard ratio, 0.88; 95% CI, 0.74 to 1.03; P<0.001 for noninferiority; P=0.12 for superiority). Major and nonmajor clinically relevant bleeding occurred in 1475 patients in the rivaroxaban group (14.9% per year) and in 1449 in the warfarin group (14.5% per year) (hazard ratio, 1.03; 95% CI, 0.96 to 1.11; P=0.44), with significant reductions in intracranial hemorrhage (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group. In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolism. There was no significant between-group difference in the risk of major bleeding, although intracranial and fatal bleeding occurred less frequently in the rivaroxaban group. (Funded by Johnson & Johnson and Bayer; ROCKET AF ClinicalTrials.gov number, NCT00403767.).
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              Dabigatran versus warfarin in patients with atrial fibrillation.

              Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor. In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism. Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051). In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. (ClinicalTrials.gov number, NCT00262600.) 2009 Massachusetts Medical Society
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                Author and article information

                Journal
                Ann Afr Med
                Ann Afr Med
                AAM
                Annals of African Medicine
                Wolters Kluwer - Medknow (India )
                1596-3519
                0975-5764
                Jul-Sep 2020
                19 August 2020
                : 19
                : 3
                : 153-163
                Affiliations
                [1 ]Department of Medicine and University of Nigeria Enugu Campus, Dedicated Anticoagulation Clinic, University of Nigeria Teaching Hospital, Enugu, Nigeria
                [2 ]Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Nigeria Enugu Campus, Dedicated Anticoagulation Clinic, University of Nigeria Teaching Hospital, Enugu, Nigeria
                Author notes
                Address for correspondence: Dr. Anakwue Raphael, Department of Pharmacology/Therapeutics, Faculty of Medical Sciences, University of Nigeria Enugu Campus, Dedicated Anticoagulation Clinic, University of Nigeria Teaching Hospital, Enugu, Nigeria. E-mail: raphael.anakwue@ 123456unn.edu.ng ; dranakwue@ 123456yahoo.com
                Article
                AAM-19-153
                10.4103/aam.aam_30_19
                7694708
                32820726
                8cd470ff-913c-4c2e-85ea-31520397e824
                Copyright: © 2020 Annals of African Medicine

                This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

                History
                : 24 June 2019
                : 12 November 2019
                : 24 February 2020
                Categories
                Review Article

                anticoagulants,models of anticoagulation service,nonvitamin k oral anticoagulants,thromboembolic diseases,warfarin,modèles de service d’anticoagulation,anticoagulants oraux sans vitamine k,maladies thromboemboliques,warfarine

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