Thromboembolic and neurologic sequelae of discontinuation of an antihyperlipidemic drug during ongoing warfarin therapy

Warfarin and antihyperlipidemics are commonly co-prescribed. Some antihyperlipidemics may inhibit warfarin deactivation via the hepatic cytochrome P450 system. Therefore, antihyperlipidemic discontinuation has been hypothesized to result in underanticoagulation, as warfarin metabolism is no longer inhibited. We quantified the risk of venous thromboembolism (VTE) and ischemic stroke (IS) due to statin and fibrate discontinuation in warfarin users, in which warfarin was initially dose-titrated during ongoing antihyperlipidemic therapy. Using 1999-2011 United States Medicaid claims among 69 million beneficiaries, we conducted a set of bidirectional self-controlled case series studies-one for each antihyperlipidemic. Outcomes were hospital admissions for VTE/IS. The risk segment was a maximum of 90 days immediately following antihyperlipidemic discontinuation, the exposure of interest. Time-varying confounders were included in conditional Poisson models. We identified 629 study eligible-persons with at least one outcome. Adjusted incidence rate ratios (IRRs) for all antihyperlipidemics studied were consistent with the null, and ranged from 0.21 (0.02, 2.82) for rosuvastatin to 2.16 (0.06, 75.0) for gemfibrozil. Despite using an underlying dataset of millions of persons, we had little precision in estimating IRRs for VTE/IS among warfarin-treated persons discontinuing individual antihyperlipidemics. Further research should investigate whether discontinuation of gemfibrozil in warfarin users results in serious underanticoagulation

PERBANDINGAN DAYA BUNUH WARFARIN 0,105% DAN BRODIFACOUM 0,005% TERHADAP MENCIT (Mus Musculus)

Tikus adalah rodensia yang berperan sebagai tuan rumah perantara untuk beberapa jenis penyakit yang dikenal sebagai penyakit tular rodensia, selain dapat menimbulkan berbagai gangguan dan kerugian ekonomi. Dalam setahun tikus mampu berbiak menjadi 50 ekor. Umpan dengan bahan aktif Warfarin 0,105% dan Brodifacoum 0,005% termasuk jenis racun yang bekerja secara lambat dan menghambat proses koagulasi serta memecah pembuluh darah kapiler. Binatang yang sering digunakan dalam penelitian di laboratorium adalah Mencit (Mus Musculus) Strain albino, sehingga dilakukan penelitian tentang perbandingan daya bunuh Warfarin 0,105% dan Brodifacoum 0,005% terhadap Mencit ( Mus Musculus). Sampel penelitian sebanyak 20 ekor untuk perlakuan Warfarin 0,105% dan 20 ekor untuk perlakuan Brodifacoum 0,005%, sedangkan seekor untuk kontrol. Metode yang digunakan adalah eksperimen murni dengan sistem randomisasi. Penelitian selama 7 hari mendapatkan data kematian Mencit karena Warfarin 0,105% mulai terjadi pada hari ke 4, sedangkan kematian mencit karena Brodifacoum 0,005% mulai terjadi pada hari ke 3. Bobot kematian terendah pada 19,4 gram dan tertinggi dengan berat 30 gram. Uji statistik dengan rancangan Acak Lengkap dan analisis ragam menunjukkan bahwa ada perbedaan daya bunuh nyata antara Warfarin 0,105% dan Brodifacoum 0,005% terhadap Mencit (Mus Musculus). Hal ini dapat dilihat dari nilai F-Hitung> nilai F-tabel pada alfa 0,05 dan 0,01 yaitu 37,69> 4,10 dan 7,35. Perbandingan daya bunuh warfarin 0,105% dan Brodifacoum 0,005% terhadap Mencit (Mus Musculus) adalah 1:8, artinya daya bunuh Brodifacoum 0,005% terhadap Mencit (Mus Musculus) 8 kali lebih besar dibandingkan Warfarin 0,105%. Warfarin 0,105% dan Brodifacum 0,005% sama-sama mempunyai daya bunuh terhadap Mencit (Mus Musculus), sehingga dapat digunakan sebagai pengendalian tikus dan mencit liar, tetapi dalam cakupan yang luas agar menggunakan Brodifacoum 0,005%. Kata Kunci: Warfarin 0,105%, Brodifacoum 0,005%, Mencit

A framework model for a contextualized and integrated warfarin therapy case in a master of pharmacy program

© Copyright 2019 American Journal of Pharmaceutical Education.Objective. To develop and integrate a case study on warfarin into a clinical pharmacy workshop. Methods. A framework model was designed and used to create a case study on warfarin therapy. The case study was implemented in a third-year Master of Pharmacy course. Student feedback was obtained using an online questionnaire and two focus groups. Results. All students agreed that the case study successfully integrated the science of warfarin and concepts of pharmacy practice. The majority of students (94%) agreed that this approach helped them to understand the science of warfarin more than a traditional lecture would have. Students felt the time allocated to the workshop was too short. Conclusion. An integrated case study provides a learning environment that emphasizes the contextualization of chemistry and pharmacology into a clinical pharmacy setting.Peer reviewedFinal Published versio

An evidence-based review of edoxaban and its role in stroke prevention in patients with nonvalvular atrial fibrillation.

Atrial fibrillation is the most common arrhythmia in the elderly. It is responsible for significant morbidity and mortality from cardioembolic complications like stroke. As a result, atrial fibrillation patients are risk-stratified using the CHADS2 or CHA2DS2-VASc scoring systems. Those at intermediate-to-high risk have traditionally been treated with therapeutic anticoagulation with warfarin for stroke prevention. Although effective, warfarin use is fraught with multiple concerns, such as a narrow therapeutic window, drug-drug and drug-food interactions, and excessive bleeding. Novel oral anticoagulant agents have recently become available as viable alternatives for warfarin therapy. Direct thrombin inhibitor dabigatran and factor Xa inhibitors like rivaroxaban and apixaban have already been approved by the US Food and Drug Administration (FDA) for stroke prevention in patients with nonvalvular atrial fibrillation. Edoxaban is the latest oral direct factor Xa inhibitor studied in the largest novel oral anticoagulant trial so far: ENGAGE AF-TIMI 48. Treatment with a 30 mg or 60 mg daily dose of edoxaban was found to be noninferior to dose-adjusted warfarin in reducing the rate of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, with a lower incidence of bleeding complications and cardiovascular deaths. Edoxaban was recently reviewed by an FDA advisory committee and recommended as a stroke-prophylaxis agent. Once approved, it promises to provide another useful alternative to warfarin therapy

ANALISA GAMBARAN POST MORTEM MAKROSKOPIS DAN MIKROSKOPIS ORGAN PARU DAN USUS HALUS PADA TIKUS WISTAR SETELAH PEMBERIAN WARFARIN LD-50 DAN LD-100

Introduction : More than 800.000 people died every years from suicide, and in 2012 suicidal acts on 15-29 years old become the second most cause. Suicide by poison is one of the most used, Warfarins role here aside from its therapeutical effect as anticoagulant, and also as rodenticide in household often misused for a way to suicide. This study is aimed to analyze the differences of macroscopic and microscopics representation in lungs and small intestine on Wistar mouse after LD50 dan LD100 Warfarin administration. Method : This is experimental analytic study, using total sample of 27 mouse, male Rattus norvegicus as the sample. These 27 mouse will be divided into 3 group, 9 eachs. First group is administered LD50 Warfarin, second group is administered LD100 Warfarin, and the third group as control. Result : there is no differences in macroscopic aspect of lung control group with group LD50 dan LD100, in microscopic showed massive haemmorhage. On small intestines there is differences from control group with LD50 dan LD100. Conclussion : Toxic effect from warfarin showed in microscopic view of organs with hemorrhage and destruction of its tissues. Keyword : Warfarin, Wistar, Macroscopic and Microscopic view. 1. Staff of Forensic Department, Faculty of Medicine Diponegoro University 2. Staff of Pathologic Anatomy Departmen, Faculty of Medicine Diponegoro University 3. Undergraduate Students, Faculty of Medicine Diponegoro University

Control of the house mouse (Mus musculus L.) in the Netherlands

Rodent control in the Netherlands is carried out by local authorities, extermination companies or the owners of infested premises. The control of the house mouse, especially in food-handling establishments, is a problem that has existed for some years. Testing in the laboratory indicates a warfarin resistance although the application of new rodenticides like bromadiolone, calciferol and difenacoum has given good results. A "manual" for the control of suspected warfarin resistant house mice is given

Patient-Reported Satisfaction and Study Drug Discontinuation: Post-Hoc Analysis of Findings from ROCKET AF.

IntroductionPatient-reported outcomes (PROs) and satisfaction endpoints are increasingly important in clinical trials and may be associated with treatment adherence. In this post hoc substudy from ROCKET AF, we examined whether patient-reported satisfaction was associated with study drug discontinuation.MethodsROCKET AF (n = 14,264) compared rivaroxaban with warfarin for prevention of stroke and systemic embolism in patients with atrial fibrillation. We analyzed treatment satisfaction scores: the Anti-Clot Treatment Scale (ACTS) and Treatment Satisfaction Questionnaire for Medication version II (TSQM II). We compared satisfaction with study drug between the two treatment arms, and examined the association between satisfaction and patient-driven study drug discontinuation (stopping study drug due to withdrawal of consent, noncompliance, or loss to follow-up).ResultsA total of 1577 (11%) patients participated in the Patient Satisfaction substudy; 1181 (8.3%) completed both the ACTS and TSQM II 4 weeks after starting study drug. Patients receiving rivaroxaban did not experience significant differences in satisfaction compared with those receiving warfarin. During a median follow-up of 1.6 years, 448 premature study drug discontinuations occurred (213 rivaroxaban group; 235 warfarin group), of which 116 (26%) were patient-driven (52 [24%] rivaroxaban group; 64 [27%] warfarin group). No significant differences were observed between satisfaction level and rates of patient-driven study drug discontinuation.ConclusionsStudy drug satisfaction did not predict rate of study drug discontinuation. No significant difference was observed between satisfaction with warfarin and rivaroxaban, as expected given the double-blind trial design. Although these results are negative, the importance of PRO data will only increase, and these analyses may inform future studies that explore the relationship between drug-satisfaction PROs, adherence, and clinical outcomes. CLINICALTRIALS.GOV: NCT00403767.FundingThe ROCKET AF trial was funded by Johnson & Johnson and Bayer

Health Care Savings from Personalizing Medicine Using Genetic Testing: The Case of Warfarin

Progress towards realizing a vision of personalized medicine - drugs and drug doses that are safer and more effective because they are chosen based on an individual's genetic makeup - has been slower than once forecast. The Food and Drug Administration has a key role to play in facilitating the use of genetic information in drug therapies because it approves labels, and labels influence how doctors use drugs. Here we evaluate one example of how using genetic information in drug therapy may improve public health and lower health care costs. Warfarin, an anticoagulant commonly used to prevent and control blood clots, is complicated to use because the optimal dose varies greatly among patients. If the dose is too strong the risk of serious bleeding increases and if the dose is too weak, the risk of stroke increases. We estimate the health benefits and the resulting savings in health care costs by using personalized warfarin dosing decisions based on appropriate genetic testing. We estimate that formally integrating genetic testing into routine warfarin therapy could allow American warfarin users to avoid 85,000 serious bleeding events and 17,000 strokes annually. We estimate the reduced health care spending from integrating genetic testing into warfarin therapy to be $1.1 billion annually, with a range of about$100 million to $2 billion.

Apixaban Enhances Endogenous Fibrinolysis in Patients with Atrial Fibrillation

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.AIMS: Approximately 20% of ischaemic stroke patients exhibit spontaneous arterial recanalization, attributable to endogenous fibrinolysis, which strongly relates to improved functional outcome. The impact of oral anticoagulants on endogenous fibrinolysis is unknown. Our aim was to test the hypothesis that apixaban enhances endogenous fibrinolysis in non-valvular atrial fibrillation (NVAF). METHODS AND RESULTS: In a prospective cross-sectional analysis, we compared endogenous fibrinolysis in NVAF patients (n = 180) taking aspirin, warfarin, or apixaban. In a prospective longitudinal study, patients were tested before and after apixaban (n = 80). Endogenous fibrinolysis was assessed using the Global Thrombosis Test (GTT) and thromboelastography (TEG). Endogenous fibrinolysis [measured by GTT lysis time (LT)] was shorter on apixaban compared with warfarin or aspirin [median 1850 (IQR 1591-2300) vs. 2758 (2014-3502) vs. 2135 (1752-2463) s, P < 0.0001]. Among TEG indices, a small but significant difference in clot lysis time (CLT) was observed [apixaban 60.0 (45.0-61.0) vs. warfarin 61.0 (57.0-62.0) vs. aspirin 61.0 (59.0-61.0) min, P = 0.036]. Apixaban improved endogenous fibrinolysis measured using the GTT [LT pre-treatment 2204 (1779-2738) vs. on-treatment 1882 (1607-2374) s, P = 0.0003], but not by using TEG. Change in LT (ΔLT) with apixaban correlated with baseline LT (r = 0.77, P < 0.0001). There was weak correlation between ΔLT and ΔCLT in response to apixaban (r = 0.28, P = 0.02) and between on-apixaban LT and CLT (r = 0.25, P = 0.022). CONCLUSION: Apixaban enhances endogenous fibrinolysis, with maximal effect in those with impaired fibrinolysis pre-treatment. Apixaban-treated patients exhibit more favourable fibrinolysis profiles than those taking warfarin or aspirin. Whether apixaban may confer additional thrombotic risk reduction in NVAF patients with impaired fibrinolysis, compared to warfarin, merits further study.Peer reviewedFinal Accepted Versio