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2.
J Med Case Rep ; 17(1): 223, 2023 May 31.
Article in English | MEDLINE | ID: covidwho-20234800

ABSTRACT

BACKGROUND: SARS-CoV-19 infection is associated with an increased risk of thrombotic events. We present a case of acute middle cerebral artery ischemic stroke in a patient with SARS-CoV-19 infection despite being on warfarin with supratherapeutic INR (International Normalized Ratio). CASE PRESENTATION: A 68-year-old Caucasian female with multiple comorbidities was admitted to the hospital with symptoms of upper respiratory tract infection. A rapid antigen test confirmed the diagnosis of COVID-19 pneumonia, and intravenous remdesivir was initiated. On the fifth day of admission, the patient experienced sudden onset confusion, slurred speech, left-sided hemiplegia, right-sided eye deviation, and left-sided facial droop. Imaging studies revealed an occlusion of the distal anterior M2 segment of the right middle cerebral artery, and an MRI of the brain confirmed an acute right MCA infarction. Notably, the patient was receiving warfarin therapy with a supratherapeutic INR of 3.2. CONCLUSIONS: This case report highlights the potential for thromboembolic events, including stroke, in patients with COVID-19 infection, even when receiving therapeutic anticoagulation therapy. Healthcare providers should be vigilant for signs of thrombosis in COVID-19 patients, particularly those with pre-existing risk factors. Further research is necessary to understand the pathophysiology and optimal management of thrombotic complications in COVID-19 patients.


Subject(s)
COVID-19 , Ischemic Stroke , Stroke , Humans , Female , Aged , Warfarin/therapeutic use , International Normalized Ratio/adverse effects , COVID-19/complications , Stroke/diagnostic imaging , Stroke/etiology , Anticoagulants/therapeutic use , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/complications
3.
Eur Heart J Cardiovasc Pharmacother ; 8(7): 738-751, 2022 Sep 29.
Article in English | MEDLINE | ID: covidwho-2326576

ABSTRACT

Awareness of racial/ethnic disparities represents a key challenge for healthcare systems that attempt to provide effective healthcare and to reduce existing inequalities in the use of and adherence to guideline-recommended cardiovascular drugs to improve clinical outcomes for cardiovascular disease (CVD). In this review, we describe important racial/ethnic differences between and within ethnic groups in the prevalence, risk factors, haemostatic factors, anti-inflammatory and endothelial markers, recurrence, and outcomes of CVD. We discuss important differences in the selection, doses, and response [efficacy and adverse drug reactions (ADRs)] in ethnically diverse patients treated with antithrombotics or lipid-lowering drugs. Differences in drug response are mainly related to racial/ethnic differences in the frequency of polymorphisms in genes encoding drug-metabolizing enzymes (DMEs) and drug transporters. These polymorphisms markedly influence the pharmacokinetics, dose requirements, and safety of warfarin, clopidogrel, and statins. This review aims to support a better understanding of the genetic differences between and among populations to identify patients who may experience an ADR or a lack of drug response, thus optimizing therapy and improving outcomes. The greater the understanding of the differences in the genetic variants of DMEs and transporters that determine the differences in the exposure, efficacy, and safety of cardiovascular drugs between races/ethnicities, the greater the probability that personalized medicine will become a reality.


Subject(s)
Cardiovascular Agents , Cardiovascular Diseases , Coronary Artery Disease , Hemostatics , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Clopidogrel , Coronary Artery Disease/drug therapy , Coronary Artery Disease/genetics , Fibrinolytic Agents/adverse effects , Humans , Imidazoles , Lipids , Organosilicon Compounds , Warfarin
4.
Rev. bras. oftalmol ; 82: e0012, 2023. tab, graf
Article in English | WHO COVID, LILACS (Americas) | ID: covidwho-2319435

ABSTRACT

ABSTRACT Cavernous sinus and superior ophthalmic vein thrombosis is a rare clinical condition, and little described in the literature. The clinical presentation is nonspecific and highly variable, and symptoms may include red eye, ophthalmoplegia, coma, and death. The main etiology results from infection of the paranasal sinuses. The final diagnosis must be made through imaging tests such as magnetic resonance imaging. We describe a case of cavernous sinus and superior ophthalmic vein thrombosis after COVID-19 infection in a 64-year-old patient with persistent ocular hyperemia and pain on eye movement. Ophthalmological examination showed preserved visual acuity, conjunctival hyperemia, dilation of episcleral vessels and retinal vascular tortuosity in the right eye. Magnetic resonance imaging confirmed the diagnosis. The association with the COVID-19 was raised, excluding other infectious causes. Enoxaparin and Warfarin were started with significant improvement in the ocular clinical presentation and maintenance of initial visual acuity after 12 months of follow-up.


RESUMO A trombose de seio cavernoso e veia oftálmica superior é uma condição clínica rara e pouco descrita na literatura. A apresentação clínica é inespecífica e altamente variável. Os sintomas podem incluir olho vermelho, oftalmoplegia, coma e morte. A etiologia principal resulta da infecção dos seios paranasais. O diagnóstico final deve ser efetuado por meio de exames de imagem, como ressonância magnética. Descrevemos um caso de trombose de seio cavernoso e veia oftálmica superior após COVID-19 em paciente de 64 anos e com quadro de hiperemia ocular persistente e dor à movimentação ocular. Ao exame oftalmológico, observou-se acuidade visual preservada, hiperemia conjuntival, dilatação de vasos episclerais e tortuosidade vascular retiniana em olho direito. A ressonância confirmou o diagnóstico. A associação com a COVID-19 foi levantada, excluindo-se demais causas infecciosas. Prescrevemos enoxaparina e varfarina, com melhora do quadro clínico ocular e manutenção da acuidade visual inicial após 12 meses de acompanhamento.


Subject(s)
Humans , Female , Middle Aged , Venous Thrombosis/etiology , Cavernous Sinus Thrombosis/etiology , COVID-19/complications , Retinal Vessels/pathology , Tonometry, Ocular , Warfarin/administration & dosage , Magnetic Resonance Imaging , Enoxaparin/administration & dosage , Conjunctiva/pathology , Venous Thrombosis/diagnosis , Venous Thrombosis/drug therapy , Cavernous Sinus Thrombosis/diagnosis , Cavernous Sinus Thrombosis/drug therapy , Slit Lamp Microscopy , SARS-CoV-2 , Anticoagulants/administration & dosage
5.
J Med Case Rep ; 17(1): 101, 2023 Mar 19.
Article in English | MEDLINE | ID: covidwho-2289166

ABSTRACT

BACKGROUND: Coronavirus disease 2019 was spread worldwide, as a pandemic, from December 2019. Venous thromboembolism events can inflict patients with coronavirus disease 2019 during the hospitalization or convalescent period. Therefore, monitoring of these patients, in terms of venous thromboembolism events signs and symptoms, and timely management of antithrombotic agents are of great importance. CASE REPORT: A 45-year-old Iranian man, who is the first author of this case report, was infected by severe acute respiratory syndrome coronavirus 2 and displayed the typical signs and symptoms of coronavirus disease 2019. Although reverse transcription polymerase chain reaction for coronavirus disease 2019, and specific immunoglobulin M and immunoglobulin G against severe acute respiratory syndrome coronavirus 2, were negative at first, chest computed tomography scan showed the characteristic pattern of lung involvement of a coronavirus disease 2019 infection including bilateral and multilobar ground-glass opacities. At that time, there were no signs or symptoms of deep-vein thrombosis or pulmonary thromboembolism, so these were not investigated. About 30 hours after hospital discharge, the patient presented back to the hospital with acute-onset chest pain. We instantly tested his blood for D-dimer, and sent him to take a Doppler sonography of his lower legs and a chest computed tomography angiography in search of pulmonary thromboembolism and deep-vein thrombosis. Although we could confirm pulmonary thromboembolism with computed tomography angiography in our patient, there were no signs or symptoms of venous thromboembolism in his lower legs, and color Doppler sonography of lower limbs was normal. So, the patient was treated with rivaroxaban as an antithrombotic agent. After some days, he was discharged in good condition. About 1 month later, he was referred to our hospital because of left lower limb edema. Although he was under antithrombotic therapy, color Doppler sonography of lower limbs revealed acute deep-vein thrombosis of the left leg. Hence, we decided to shift antithrombotic therapy from rivaroxaban to warfarin, as it is more potent than rivaroxaban in recurrent venous thromboembolism and when taking new oral anticoagulants. Unlike rivaroxaban, which needs no blood test to monitor its efficacy but has a warning for signs and symptoms of bleeding, warfarin therapy must be monitored carefully by regular blood tests for prothrombin time and international normalized ratio to maintain them in the therapeutic range. The patient was informed about the bleeding cautions, and required regular check of prothrombin time and international normalized ratio to maintain them in the proper and advised range of treatment (international normalized ratio therapeutic range 2-3). CONCLUSION: In the case of unexpected recurrent venous thromboembolism in coronavirus disease 2019, especially when patients are taking rivaroxaban or other new oral anticoagulants, such drugs should be substituted by warfarin, with routine follow-up, to maintain the value of prothrombin time and international normalized ratio within the therapeutic range.


Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Venous Thrombosis , Male , Humans , Middle Aged , Warfarin/therapeutic use , Venous Thromboembolism/diagnostic imaging , Venous Thromboembolism/drug therapy , Venous Thromboembolism/etiology , Rivaroxaban/therapeutic use , COVID-19/complications , Fibrinolytic Agents/therapeutic use , Iran , Anticoagulants , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy , Venous Thrombosis/etiology , Pulmonary Embolism/diagnostic imaging , Pulmonary Embolism/drug therapy , Pulmonary Embolism/complications , Hemorrhage/chemically induced , SARS-CoV-2 , Decision Making
6.
Ren Fail ; 45(1): 2163505, 2023 Dec.
Article in English | MEDLINE | ID: covidwho-2260044

ABSTRACT

PURPOSE: The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. MATERIALS AND METHODS: This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. RESULTS: No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p < .05). Finally, adverse events were more frequent in warfarin-treated patients. CONCLUSIONS: This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17013428.


Subject(s)
Atrial Fibrillation , Nephrotic Syndrome , Thromboembolism , Adult , Humans , Warfarin/adverse effects , Fibrinolytic Agents/therapeutic use , Nephrotic Syndrome/complications , Nephrotic Syndrome/drug therapy , Nephrotic Syndrome/chemically induced , Anticoagulants , Thromboembolism/prevention & control , Thromboembolism/chemically induced , Hemorrhage/chemically induced , Hemorrhage/complications , Treatment Outcome
7.
Transplantation ; 106(11): 2143-2154, 2022 11 01.
Article in English | MEDLINE | ID: covidwho-2278350

ABSTRACT

Direct-acting oral anticoagulant (DOAC) use has increased dramatically since their introduction because of the growing evidence of proven efficacy and enhanced safety compared with warfarin and the low-molecular-weight heparins in the general population. Unfortunately, there is a dearth of quality data regarding the safety and efficacy of the DOACs in patients awaiting organ transplant and those who received a solid organ transplant. This review aims to evaluate the available literature and considerations regarding anticoagulation use in transplant recipients, focusing on preoperative, perioperative, and postoperative DOAC use.


Subject(s)
Organ Transplantation , Warfarin , Humans , Factor Xa Inhibitors , Anticoagulants/adverse effects , Administration, Oral , Organ Transplantation/adverse effects , Heparin, Low-Molecular-Weight
8.
Turk Kardiyol Dern Ars ; 50(8): 576-582, 2022 12.
Article in English | MEDLINE | ID: covidwho-2155680

ABSTRACT

BACKGROUND: COVID-19 is associated with vascular thrombosis in critical patients. However, warfarin has not been adequately studied in patients with COVID-19. This study aimed to evaluate whether the use of warfarin, a potent oral anticoagulant, was of clinical benefit in patients with COVID-19. METHODS: This was a retrospective cohort study of COVID-19 patients diagnosed at 3 different centers in Turkey between April 2020 and April 2021. Patients were grouped by whether they were taking warfarin or not. Propensity score matching analysis was used to compare the dif ferences between the groups in mortality, hospitalization, and admission to the intensive care unit. RESULTS: A propensity score analysis was performed on 128 patients in the warfarin group and 372 patients in the control group. After matching, 84 pairs of patients were compared. The patients in the control group were more likely to be admitted to the intensive care unit (33.3% vs. 14.3%, respectively; P=.007) and had longer hospital stays than the warfarin group (7.1 vs. 14.1 days; P=.005). The warfarin group had a lower death rate compared to the control group (7.1% vs. 27.4%, respectively; P=.001), and surviving patients were sig nificantly more likely to be in the warfarin group than the control group (56.1% vs. 20.7%, respectively; P=.001). In patients on warfarin, there was a lower incidence of in-hospital death (log-rank test P=.005). CONCLUSIONS: Warfarin therapy could provide clinical benefits in patients with COVID-19. The current data highlight the importance of potent anticoagulation in the treatment of COVID-19.


Subject(s)
COVID-19 , Warfarin , Humans , Hospital Mortality , Retrospective Studies , Warfarin/therapeutic use
9.
J Am Soc Nephrol ; 33(2): 442-453, 2022 02.
Article in English | MEDLINE | ID: covidwho-2141040

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large "real-world" contemporary population with incident AF to study the association of CKD with management of AF. METHODS: We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45-59, 30-44, 15-29, <15 ml/min per 1.73 m2) was calculated from a minimum of two ambulatory serum creatinine measures separated by ≥90 days. AF medications and procedures were identified from electronic health records. We performed multivariable Fine-Gray subdistribution hazards regression to test the association of CKD severity with receipt of targeted AF therapies. RESULTS: Among 115,564 patients with incident AF, 34% had baseline CKD. In multivariable models, compared with those with eGFR >60 ml/min per 1.73 m2, patients with eGFR 30-44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15-29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and <15 ml/min per 1.73 m2 (aHR, 0.64; 95% CI, 0.58-0.70) had lower use of any AF therapy. Patients with eGFR 15-29 ml/min per 1.73 m2 had lower adjusted use of rate control agents (aHR, 0.61; 95% CI, 0.56 to 0.67), warfarin (aHR, 0.89; 95% CI, 0.84 to 0.94), and DOACs (aHR, 0.23; 95% CI, 0.19 to 0.27) compared with patients with eGFR >60 ml/min per 1.73 m2. These associations were even stronger for eGFR <15 ml/min per 1.73 m2. There was also a graded association between CKD severity and receipt of AF-related procedures (vs eGFR >60 ml/min per 1.73 m2): eGFR 30-44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15-29 ml/min per 1.73 m2 (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR <15 ml/min per 1.73 m2 (aHR, 0.48; 95% CI, 0.31 to 0.74). CONCLUSIONS: In adults with newly diagnosed AF, CKD severity was associated with lower receipt of rate control agents, anticoagulation, and AF procedures. Additional data on efficacy and safety of AF therapies in CKD populations are needed to inform management strategies.


Subject(s)
Atrial Fibrillation/complications , Atrial Fibrillation/therapy , Renal Insufficiency, Chronic/complications , Adult , Aged , Aged, 80 and over , Anti-Arrhythmia Agents/therapeutic use , Anticoagulants/therapeutic use , Atrial Fibrillation/drug therapy , Cohort Studies , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Multivariate Analysis , Renal Insufficiency, Chronic/physiopathology , Severity of Illness Index , Warfarin/therapeutic use
10.
Ann Saudi Med ; 42(5): 305-308, 2022.
Article in English | MEDLINE | ID: covidwho-2080739

ABSTRACT

BACKGROUND: COVID-19 infection affects the quality of the medical services globally. The pandemic required changes to medical services in several institutions. We established a virtual clinic for anticoagulation management during the pandemic using the Whatsapp application. OBJECTIVES: Compare anticoagulation management quality in virtual versus in-person clinics. DESIGN: A retrospective crossover study SETTINGS: Specialized cardiac care center PATIENTS AND METHODS: The study included patients who presented to Prince Sultan Cardiac Center in Riyadh for anticoagulation management during the pandemic from March 2020 to January 2021. We compared time in therapeutic range (TTR) in the same patients during virtual and in-person clinics. All international normalized ratio (INR) measures during the virtual clinic visits and prior ten INR measures from the in-person clinic were recorded. Patients who had no prior follow-up in the in-person clinic were excluded. MAIN OUTCOME MEASURE: TTR calculated using the Rosendaal method. SAMPLE SIZE: 192 patients RESULTS: The mean age was 58.6 (16.6) years and 116 (60.4%) were males. Patients were diagnosed with atrial fibrillation (n=101, 52.6%), mechanical mitral valve (n=88, 45.8%), mechanical aortic valve (n=79, 41%), left ventricular thrombus (n=5, 2.6%) and venous thromboembolism (n=8, 4.2%). Riyadh residents represented 56.7% of the study population (n=93). The median (IQR) percent TTR was 54.6 (27.3) in the in-person clinic versus 50.0 (33.3) (P=.07). CONCLUSION: Virtual clinic results were comparable to in-person clinics for anticoagulation management during the COVID-19 pandemic. LIMITATIONS: Number of INR measures during the virtual clinic visits, retrospective nature and single-center experience. CONFLICT OF INTEREST: None.


Subject(s)
COVID-19 , Warfarin , Anticoagulants/therapeutic use , Cross-Over Studies , Female , Humans , Male , Middle Aged , Pandemics , Retrospective Studies , Warfarin/therapeutic use
11.
Yakugaku Zasshi ; 142(10): 1125-1127, 2022.
Article in Japanese | MEDLINE | ID: covidwho-2054202

ABSTRACT

A 55-year-old man with hypertrophic cardiomyopathy and a pacemaker was admitted with coronavirus disease 2019 (COVID-19). Before admission, the patient's medications included amiodarone, diltiazem, bisoprolol, atorvastatin, etizolam, and warfarin (WF). After admission, dexamethasone (DXM) and remdesivir (RDV) were initiated for treating COVID-19. The international normalized ratio (INR) on admission was 1.8, which increased to 3.4 on day 5 and to 6.9 on day 10 after admission. Although there have been reports that RDV may occasionally prolong prothrombin time and that the degree of prolongation is often less severe, the mechanism of action has not been elucidated till date. There are reports of prolonged INR when WF is co-administered with RDV and DXM, suggesting that drug interactions may be a potential cause for the prolongation. A similar drug interaction may have potentially occurred in the case reported here. In addition, this case used amiodarone (AMD), and it has been reported that the RDV concentration increases when used in combination with AMD. Further investigations are needed to elucidate the cause of INR prolongation. Thus, close monitoring of the patient is recommended when RDV is co-administered with high-risk agents to avoid unnecessary side effects.


Subject(s)
Amiodarone , COVID-19 Drug Treatment , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Amiodarone/adverse effects , Anticoagulants/pharmacology , Atorvastatin , Bisoprolol , Dexamethasone/adverse effects , Diltiazem , Drug Interactions , Humans , International Normalized Ratio , Male , Middle Aged , Warfarin/pharmacology
12.
J Cardiovasc Pharmacol Ther ; 27: 10742484221128124, 2022.
Article in English | MEDLINE | ID: covidwho-2053690

ABSTRACT

BACKGROUND: Because of logistic challenges associated with the COVID-19 pandemic, direct oral anticoagulants (DOAC) were favored over warfarin in patients presenting postoperative atrial fibrillation (AF) after cardiac surgery in our institution. Considering the limited evidence supporting the use of DOAC in this context, we sought to evaluate the safety and efficacy of this practice change. METHODS: A retrospective study was performed with patients from the Quebec City metropolitan area who were hospitalized at the Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval following cardiac surgery and who required oral anticoagulant (OAC) for postoperative AF. The primary objective was to compare the pre- and peri-COVID-19 period for OAC prescribing patterns and the incidence of thrombotic and bleeding events at 3 months post-surgery. The secondary objective was to compare DOAC to warfarin in terms of thrombotic events and bleeding events. RESULTS: A total of 233 patients were included, 142 from the pre-COVID-19 and 91 from the peri-COVID-19 period, respectively. Both groups had equivalent proportions of preoperative AF (48%) and new-onset postoperative AF (52%). The proportion of patients treated with a DOAC increased from 13% pre-COVID-19 to 82% peri-COVID-19. This change in practice was not associated with a significant difference in the incidence of thrombotic or bleeding events 3 months postoperatively. However, compared to DOAC, warfarin was associated with a higher incidence of major bleeding. Only 1 thrombotic event was reported with warfarin, and none were reported with DOAC. CONCLUSION: This study suggests that DOAC are an effective and safe alternative to warfarin to treat postoperative AF after cardiac surgery and that this practice can be safely maintained.


Subject(s)
Atrial Fibrillation , COVID-19 , Cardiac Surgical Procedures , Stroke , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Atrial Fibrillation/epidemiology , Cardiac Surgical Procedures/adverse effects , Hemorrhage/chemically induced , Hemorrhage/epidemiology , Humans , Pandemics , Retrospective Studies , Stroke/epidemiology , Warfarin/adverse effects
15.
Thromb Res ; 217: 52-56, 2022 09.
Article in English | MEDLINE | ID: covidwho-1937244

ABSTRACT

INTRODUCTION: Patients taking warfarin require frequent international normalized ratio (INR) monitoring in healthcare settings, putting them at increased risk of Coronavirus disease 2019 (COVID-19) exposure during the pandemic. Thus, strategies to limit in-person visits to healthcare facilities were recommended by the Anticoagulation Forum. The objective of this study was to describe the number and types of changes made to anticoagulation therapy as a result of pharmacist intervention during the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective chart review of patients included in a primary care COVID-19 anticoagulation intervention was conducted. During this intervention, pharmacists provided individualized recommendations for anticoagulation changes in patients taking warfarin to limit their healthcare facility exposure while also maintaining safe anticoagulation management practices. RESULTS: As a result of pharmacist intervention, 83 (55.7 %) of the 149 patients included in the intervention had changes in anticoagulation including: switching to a direct oral anticoagulant (n = 12), extending the INR monitoring interval (n = 48), switching to home INR monitoring (n = 21), or stopping anticoagulation (n = 2). For those patients who were taking warfarin for the entire 6 months pre- and post-intervention, the total number of healthcare facility and laboratory visits with an INR completed decreased from 8.8 to 6.4 (p < 0.001) per patient without a statistically significant decrease in time in therapeutic range (p = 0.76). CONCLUSIONS: This study depicts rapid implementation of a population health-based approach to assess all patients taking warfarin for options to minimize healthcare visits and decrease risk for COVID-19 exposure. Methods to reduce healthcare visit burden while maintaining patient safety should be considered as a regular component of anticoagulation management post-pandemic.


Subject(s)
COVID-19 , Warfarin , Anticoagulants/adverse effects , Drug Monitoring/methods , Humans , International Normalized Ratio/methods , Pandemics , Pharmacists , Retrospective Studies , Warfarin/adverse effects
17.
Clin Pharmacol Ther ; 112(4): 803-807, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1925900

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) with cardiovascular diseases who are at higher risk of progressing to critical illness should be treated with nirmatrelvir/ritonavir (Paxlovid). Ritonavir, the booster in nirmatrelvir/ritonavir, modulates multiple drug metabolizing enzymes and transporters, complicating its use in real-world clinics. We aimed to apply physiologically-based pharmacokinetic (PBPK) modeling to simulate the complex drug-drug interactions (DDIs) of ritonavir with two anticoagulants, rivaroxaban and racemic warfarin, to address this important clinical conundrum. Simulations were implemented within Simcyp Simulator. Compound and population models were adopted from Simcyp and our previous studies. Upon verification and validation of the PBPK model of ritonavir, prospective DDI simulations with the anticoagulants were performed in both the general population (20-65 years) and geriatric subjects (65-85 years) with or without moderate renal impairment. Elevated rivaroxaban concentrations were simulated with nirmatrelvir/ritonavir treatment, where the impact was more profound among geriatric subjects with renal impairment. The overexposure of rivaroxaban was restored to normal range on day 4 post-discontinuation of nirmatrelvir/ritonavir, corroborating with the recovery of enzyme activity. A lower 10 mg daily dose of rivaroxaban could effectively maintain acceptable systemic exposure of rivaroxaban during nirmatrelvir/ritonavir treatment. Treatment of ritonavir marginally declined simulated S-warfarin concentrations, but substantially elevated that of R-warfarin, resulting in a decrease in the international normalized ratio (INR). As INR only recovered 2 weeks post-nirmatrelvir/ritonavir treatment, a longer surveillance INR for warfarin becomes important. Our PBPK-guided simulations evaluated clinically important yet untested DDIs and supports clinical studies to ensure proper anticoagulation management of patients with COVID-19 with chronic coagulative abnormalities when initiating nirmatrelvir/ritonavir therapy.


Subject(s)
COVID-19 Drug Treatment , Ritonavir , Aged , Anticoagulants/adverse effects , Drug Combinations , Drug Interactions , Humans , Lactams , Leucine , Nitriles , Proline , Prospective Studies , Ritonavir/pharmacokinetics , Ritonavir/therapeutic use , Rivaroxaban/pharmacokinetics , Warfarin
18.
Thromb Haemost ; 122(4): 471-474, 2022 04.
Article in English | MEDLINE | ID: covidwho-1915319
19.
Curr Med Res Opin ; 38(7): 1081-1092, 2022 07.
Article in English | MEDLINE | ID: covidwho-1852695

ABSTRACT

BACKGROUND: Direct-acting oral anticoagulants (DOACs) were developed as an alternative to warfarin to treat and prevent thromboembolism, including stroke prevention in non-valvular atrial fibrillation patients. The COVID-19 pandemic could increase the risk of stroke and/or the risk of bleeding in patients due to nonadherence or sub/supra-optimal dosing. OBJECTIVE: To investigate DOAC prescription trends in England's community settings during the complete first wave of COVID-19 pandemic. METHODS: Descriptive and interrupted time series (ITS) analyses were conducted to examine the prescription patterns of DOACs (dabigatran, rivaroxaban, apixaban and edoxaban) and warfarin for primary care patients in the English Prescribing Dataset from January 2019 to February 2021, with March 2020 as the cut-off point. RESULTS: A 19% increase in mean DOAC's accompanied with 20% warfarin prescriptions decline was observed. ITS modelling showed an increase in DOAC prescription volume in March 2020 (+7 million items, p = 0.008). The pre-existing upward trend in DOAC prescriptions slowed during the period (-427,000 items, p = 0.007). Apixaban was the most frequently used DOAC and had the largest step-change in March 2020 (+5 million items, p = 0.010). The mean monthly combined cost of DOACs and warfarin was higher during the period. DOAC prescription trends were consistent across England's regions. Conclusion: The overall oral anticoagulants use in this period was lower than expected, indicating a medical needs gap, possibly due to adherence issues. The potential clinical and logistical consequences warrant further study to identify contributing factors and mitigate avoidable risks.


Subject(s)
Atrial Fibrillation , COVID-19 , Stroke , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/drug therapy , Dabigatran/adverse effects , England/epidemiology , Factor Xa Inhibitors/therapeutic use , Fibrinolytic Agents , Humans , Interrupted Time Series Analysis , Pandemics , Prescriptions , Pyridones/adverse effects , Rivaroxaban/adverse effects , Stroke/drug therapy , Stroke/epidemiology , Stroke/prevention & control , Vitamin K , Warfarin/adverse effects
20.
Thromb Res ; 215: 14-18, 2022 07.
Article in English | MEDLINE | ID: covidwho-1821499

ABSTRACT

Anticoagulation with Vitamin K antagonists (VKA) has always posed challenges in terms of monitoring requirements. These challenges were further exacerbated in the setting of the COVID-19 pandemic, with limited access to and/or avoidance of laboratory testing. The importance of utilizing point of care (POC) health technology for individualized patient management is salient. The foundation of effective home INR monitoring is establishing patient knowledge about their therapy and INR testing proficiency. The eKITE series was developed to support patients in establishing foundational knowledge required for VKA (warfarin) management and INR monitoring. The primary objectives were to evaluate eKITE, a patient-oriented innovative online education program for warfarin therapy, participant learning stress, and patient preference for online learning. This multi-center prospective study provided patients access to warfarin online education. Participants were required to complete written quizzes assessing warfarin knowledge of key concepts proficiency and identifying knowledge deficits. Patient preference, evaluating calm (lack of anxiety) while learning, and an INR on a home meter was completed. Participants performed INR tests at home and reported INRs by telephone. The analysis included 144 children and caregivers enrolled at five US and CDN sites. Most indications for anticoagulation were cardiac (congenital or acquired heart disease) with varied INR target ranges. Mean knowledge scores for warfarin and INR self-testing modules were 97%, with low anxiety with TTR of 84%. Patient preferred online learning. eKITE is an effective teaching modality for warfarin/home INR monitoring with safe INR testing and warfarin management that is appropriate for pediatrics and adults alike. PROLOGUE: The whir in the hallways is deafening. Lights bright, alarms are ringing in a chorus of unsynchronized beeps and screeches. It has been more than a week since I have slept. Snuggled beside me is my precious child, whining and equally irritated with the asynchronous symphony, further compounded by anxiety, procedures, and pain. The sun has broken. The staff smiles are welcoming and incessant, as one after one, they approach hurried, urgent, assiduous, their need to coach me for our upcoming departure to the warmth of home. Each provides essential information that I will require to keep my child, my treasure, safe and healthy. Yet, my eyes are heavy, blurred, and my brain foggy, trapped in a dark heavy cloud. How am I to follow? Comprehend? and retain anything? As they instruct, my precious child yearns for loving arms, compassion and love, whining, crying in disquiet. Overwhelmed does not adequately describe my ineffable exhaustion. Amidst this, how am I to learn about warfarin? Such a challenging medication, with so much to know. Concentrate, I tell myself, focus; now is my only opportunity to learn. I must be alert. It seems to be nonsensical.


Subject(s)
COVID-19 Drug Treatment , Education, Distance , Adult , Anticoagulants/therapeutic use , Child , Fibrinolytic Agents/therapeutic use , Humans , International Normalized Ratio/methods , Pandemics , Prospective Studies , Warfarin/therapeutic use
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