International Normalized Ratio Monitoring Research Articles

Mechanical valve replacement for patients with rheumatic heart disease: the reality of INR control in Africa and beyond.

The majority of patients requiring heart valve replacement in low- to middle-income countries (LMICs) need it for rheumatic heart disease (RHD). While the young age of such patients largely prescribes replacement with mechanical prostheses, reliable anticoagulation management is often unattainable under the prevailing socioeconomic circumstances. Cases of patients with clotted valves presenting for emergency surgery as a consequence of poor adherence to anticoagulation control are frequent. The operative mortality rates of reoperations for thrombosed mechanical valves are several times higher than those for tissue valves, and long-term results are also disappointing. Under-anticoagulation prevails in these regions that has clearly been linked to poor international normalised ratio (INR) monitoring. In industrialised countries, safe anticoagulation is defined as >60%-70% of the time in the therapeutic range (TTR). In LMICs, the TTR has been found to be in the range of twenty to forty percent. In this study, we analysed >20,000 INR test results of 552 consecutive patients receiving a mechanical valve for RHD. Only 27% of these test results were in the therapeutic range, with the vast majority (61%) being sub-therapeutic. Interestingly, the post-operative frequency of INR tests of one every 3-4 weeks in year 1 had dropped to less than 1 per year by year 7. LMICs need to use clinical judgement and assess the probability of insufficient INR monitoring prior to uncritically applying Western guidelines predominantly based on chronological age. The process of identification of high-risk subgroups in terms of non-adherence to anticoagulation control should take into account both the adherence history of >50% of patients with RHD who were in chronic atrial fibrillation prior to surgery as well as geographic and socioeconomic circumstances.

Comprehensive Management of Anticoagulants Induced Decompensated Severe Anemia in Postmitral Valve Replacement

Abstract Mechanical prosthetic valve needs consideration for anticoagulation. The objective of this case report was to know how maintenance of oral anticoagulant therapy is very important in patients, especially with mechanical heart valve replacement. It is the holistic management of mitral valve replacement (MVR) patients with high international normalized ratio (INR) (>100), which led bleeding into the peritoneal cavity and causes decompensated severe anemia. Although it is a rare presentation for a patient of MVR with high INR level but which is most commonly presented for cerebrovascular accident. Anemia is a thoughtful worldwide problem that disturbs the quality of life in persons of all ages. A 28-year-old Indian woman with follow-up case of post-MVR came to the hospital with complaints of breathing difficulty, altered sensorium, pulse rate of 150–170 bpm (beats/min) irregularly irregular, blood pressure (80/50 mmHg), palpitation, and abdominal pain. Blood test report revealed her hemoglobin (Hb) was 3.2 g%, suggestive of severe anemia, INR was >100 s. Hence, patient diagnosed as follow-up case of MVR (#27 mm mechanical bileaflet mitral valve prosthesis) with peritoneal bleeding, an oral anticoagulant with decompensated severe anemia managment should be done. Ended the progression of her hospitalization, she received four units of packed red blood cell transfusions; Vitamin K was given intravenous once daily for 2 days and no anticoagulant was given, so far, INR was high with serial monitoring of INR and Hb. Her symptoms of breathing difficulty, pain in abdomen, weakness and giddiness resolute by the finish of her hospital stay, and she recompensed to her oral anticoagulant therapy with improved Hb and hemodynamics. Disapprovingly high INR levels are classically related with bleeding disorders revealed on imperative indicators and hemodynamic variability. To our understanding, one of the lowermost noted Hb is because of bleeding due to very high INR, so monitoring of therapeutic INR level with anticoagulants is very-very important.

A qualitative study exploring patient experiences and opinions of warfarin patient self‐management in the US healthcare system

AbstractBackgroundDespite consensus guideline recommendations, the use of warfarin patient self‐management (PSM) in the United States (US) healthcare system remains underutilized.ObjectivesTo gain an understanding of the barriers and facilitators to warfarin PSM in US healthcare systems through qualitative exploration of the opinions of select US patients receiving warfarin therapy.MethodsIndividual patient interviews were conducted at five geographically diverse sites. Grounded theory analysis was performed on interview transcriptions using the consolidated framework for implementation research (CFIR) to identify facilitators and barriers to PSM implementation within the US healthcare system.ResultsA total of 40 patients were interviewed. Four major themes emerged from the interviews: (1) “Patients are resourceful problem solvers who know themselves better than clinicians” (CFIR domain “Characteristics of Individuals”); (2) The provider‐patient relationship is key to successful PSM (CFIR domains “Inner Setting” and “Intervention Characteristics”); (3) Patients are willing and interested in trying PSM if not already doing so (CFIR domains “Process,” “Intervention Characteristics,” “Inner Setting, and “Characteristics of Individuals”); and (4) Point‐of‐care international normalized ratio (INR) monitoring is an important PSM facilitator (CFIR “Intervention Characteristics,” “Outer Setting,” “Inner Setting,” and “Process” domains).ConclusionsInterview participants were willing and interested in trying PSM. Core elements of warfarin PSM include timely access to INR results, and a framework to support PSM decision making. Home INR monitoring is likely ideal for facilitating PSM implementation as is maintaining strong provider‐patient relationships where providers, including clinical pharmacists, trust their patients and act as a safety net for PSM decision making.

Position Statement on In-hospital/Clinic Point-of-care Coagulation Testing for Anticoagulation Monitoring in Saudi Arabia.

Hospital overload is a persistent occurrence in daily practice. Interventions such as point-of-care testing (POCT) are needed to alleviate the pressure faced by healthcare providers and administrators. An invited panel of experts from Saudi Arabia was formed under the auspices of the Saudi Heart Association in order to discuss local treatment gaps in the management of patients receiving anticoagulation therapy. This was done in a series of meetings, which resulted in the development of official recommendations for the implementation of POCT for anticoagulation monitoring in the country. Recommendations were based on a comprehensive literature review and international guidelines taking into consideration local clinical practice, clinical gaps, and treatment/testing availabilities. Vitamin K antagonist (VKA)-based anticoagulation therapy requires routine monitoring. POCT is a promising model of care for the monitoring of International Normalized Ratio (INR) in patients receiving oral anticoagulation in terms efficacy, safety and convenience. The availability of POC INR testing should not replace the use of standard laboratory anticoagulation monitoring. However, there are several indications for implementing POCTINR monitoring that was agreed upon by the expert panel. POCT for anticoagulation monitoring should primarily be used in the warfarin (or other VKA) monitoring clinic in order to ensure treatment efficiency, cost-effectiveness of care, patient satisfaction, and quality of life improvement. The expert panel detailed the requirements for the establishment of a warfarin (or other VKA) monitoring clinic in terms of organization, safety, quality control, and other logistic and technical considerations. The limitations of POCT should be recognized and recommendations on best practices should be strictly followed. Core laboratory confirmation should be sought for patients with higher INR results (>4.7) on POCT. Proper training, quality control, and regulatory oversight are also critical for preserving the accuracy and reliability of POCT results. POCT enables more rapid clinical decision-making in the process of diagnosis (rule-in or rule-out), treatment choice and monitoring, and prognosis, as well as operational decision-making and resource utilization. POCT thus can fulfill an important role in clinical practice, particularly for patients receiving VKAs.

The Importance of International Normalized Ratio Monitoring in Patients With Mechanical Pulmonary Valve Prosthesis.

The most challenging risk of mechanical valves is thromboembolic events; therefore, life-long anticoagulation therapy is necessary. Anticoagulation therapy should be adjusted for each patient with serial international normalized ratio (INR) monitoring. Due to the small number of patients with a mechanical valve in the pulmonary position, we are facing a lack of information about the therapeutic range of the INR in these patients. We aimed to evaluate patients with a history of pulmonary valve replacement (PVR) who faced malfunction and compare their INR and echocardiographic data at the time of malfunction and 3 months prior. In this cross-sectional study, 71 patients who had previously undergone PVR and presented to Shaheed Rajaie Cardiovascular Medical and Research Center with a diagnosis of pulmonary valve malfunction between 2014 and 2021 were included. Patients' INR and echocardiographic data at the time of the malfunction and 3 months before the malfunction diagnosis were gathered from the hospital's registry. IBM SPSS 20.0 was used for data analysis. In this cross-sectional study, 71 patients with mechanical pulmonary valve malfunction were included. 49.3% (n = 35) were men, 50.7% (n=36) were women, and their mean age was 33.23 (±8.279). The mean INR of all patients 3 months before malfunction and at the time of malfunction was 2.29 (±0.753) and 2.20 (±0.704), respectively. In this study, most of our patients had an INR below the therapeutic range, both at the time of malfunction and 3 months prior. It emphasizes the importance of patient follow-up and keeping the INR in the therapeutic range.

Trends in use of Direct Oral Anticoagulants and Warfarin in Atrial Fibrillation Patients

Treatments used in atrial fibrillation therapy, such as those of anticoagulants, consist of vitamin K antagonists (warfarin) and direct oral anticoagulants (dabigatran, apixaban, rivaroxaban, and edoxaban). The use of warfarin requires regular monitoring of prothrombin time (PT) and international normalised ratio (INR). The therapeutic dose range is narrow, but the price is cheaper. Oral anticoagulants are directed, the incidence of major bleeding is lower, ease of use, food and drug interactions are minor, the half-life is shorter, and there is a lack of laboratory monitoring needs. Based on this problem, researchers conducted a study to determine the trend of using warfarin and oral anticoagulants in patients with atrial fibrillation at a public hospital in Jakarta. This study uses a qualitative approach, with longitudinal methods and retrospective data using outpatient medical records for the period 2014 to 2018. The trend of using warfarin anticoagulants decreased from 82.3% in 2014 to 62% in 2016, while oral anticoagulants were reduced. Direct oral anticoagulants are rivaroxaban and dabigatran, which are more widely used than apixaban, and edoxaban; no data on their use has been obtained. The opposite was true from 2017 to 2018, when the use of warfarin increased and caused a decrease in the use of direct oral anticoagulants. This research is expected to contribute to various parties, both health practitioners and academics, in terms of selecting therapies for atrial fibrillation.

Critical Appraisal on the Role of Warfarin in the Current Era.

Warfarin has been the most extensively used oral anticoagulant (OAC) in medical settings for over 60 years. Its uses, potential adverse effects, and methods for reversing its effects have been firmly established, rendering it a routine medication in medical settings where most professionals feel at ease employing it. Compared to other vitamin K antagonists (VKAs), such as acenocoumarol, warfarin offers benefits like diminished prothrombin time (PT) assays leading to enhanced oral anticoagulation. Observations over the past few years have seen the inclusion of novel/direct OACs (NOACs/DOACs) in the anticoagulant armamentarium. Although DOACs have several advantages, warfarin still has an important role in subsets of patients where DOACs are contraindicated, not well-tolerated, or cannot afford DOACs due to higher costs. Moreover, there are patient profiles where warfarin is still considered a superior choice compared to DOACs, such as age group of >75 years, kidney failure with creatinine clearance (CrCl) below 30 mL/minute, and prosthetic mechanical valve replacement. Precise management of the international normalized ratio (INR) is crucial for the effectiveness of warfarin treatment. INR monitoring is the major concern in the Indian context due to the lack of laboratories for standardized measurement. Adopting strategies such as point-of-care INR monitoring devices and anticoagulation clinics can help to improve clinical outcomes with warfarin therapy. The present review provides a critical overview of the role of warfarin therapy in the current OAC arsenal and strategies for improving therapeutic control and patient adherence. How to cite this article: Nair T. Critical Appraisal on the Role of Warfarin in the Current Era. J Assoc Physicians India 2023;71(10):31-36.

PB0435 Interference in Point-of-Care International Normalized Ratio Monitoring in Patients with Lupus Anticoagulant is Correlated with Anti-β2-Glycoprotein I Antibody Titers

PB0435 Interference in Point-of-Care International Normalized Ratio Monitoring in Patients with Lupus Anticoagulant is Correlated with Anti-β2-Glycoprotein I Antibody Titers

Optimization of anticoagulant therapy in patients undergoing mechanical heart valve replacement

Acquired heart defects have a high prevalence among patients of different age groups and represent a significant social problem. To date, surgery remains the only effective option to treat acquired heart disease, and replacement of the dysfunctional heart valves frequently relies on mechanical prosthetic heart valves which implantation requires lifelong anticoagulant therapy with vitamin K antagonists and constant monitoring of international normalised ratio. However, the optimal target range for international normalised ratio values remains poorly defined. Optimisation of the approaches to anticoagulant therapy for this category of patients is becoming increasingly important. This paper highlights the main problems and possible solutions for patients who have undergone implantation of mechanical heart valves and need constant intake of vitamin K antagonists.

Dentistry and thromboembolic risk: Strategies for effective patient care

Thromboembolic events represent a significant healthcare concern, encompassing conditions such as deep vein thrombosis, pulmonary embolism, stroke, and myocardial infarction. The management of patients with a history of thromboembolic events in the dental setting requires careful consideration and collaboration between dentists and healthcare providers. This review article delves into the intricate relationship between thromboembolic events and dentistry.We explore the importance of patient assessment, emphasizing the need for a comprehensive evaluation of medical history, risk factors, and medication regimens. Special attention is given to anticoagulant therapy, and the role of International Normalized Ratio (INR) monitoring in maintaining safe levels of anticoagulation during dental procedures. We discuss the critical timing of dental interventions and the use of local hemostatic measures to minimize bleeding risk.By elucidating these key aspects, this review article aims to provide dental professionals with a comprehensive understanding of thromboembolic events in dentistry, fostering safe and effective oral healthcare for this patient population.

A quality-improvement initiative to convert patients from warfarin to non-vitamin K antagonist oral anticoagulants.

Non-vitamin K antagonist oral anticoagulants (NOACs) are favorable in stroke prevention for geriatric patients with nonvalvular atrial fibrillation versus warfarin. These anticoagulants do not require international normalized ratio (INR) monitoring and have lower food/drug interactions. In addition, NOACs have risk reduction in bleeding and all-cause mortality compared with warfarin. At a geriatric primary care practice, two registered nurses manage 88 patients on warfarin for INR monitoring. Nurse practitioners (NPs) provide oversight for warfarin titration after abnormal results. The goal of this quality-improvement project was to decrease the time spent monitoring patients on warfarin. Primary care providers and cardiologists of patients on warfarin were contacted to gain approval of transition to a NOAC. The NP reviewed patients' renal function and the indication for anticoagulation and then created a list of eligible patients for transition. Patients eligible for transition to NOACs were contacted for their consent. The transition process included stopping warfarin, ordering apixaban, ordering INR level, educating about starting apixaban, and coordinating appropriate follow-up. Of 88 patients on warfarin, 21 were eligible for conversion from warfarin to apixaban. Of these 21 patients, 66% (n = 14) consented to the conversion. Of those who were not converted to apixaban, five declined due to cost and two were lost to follow-up. There was a reduction in nurses' monthly monitoring of patients on warfarin by 22%. Transition to NOAC was not only beneficial for patient safety and efficacy but also reduced nursing clinical time for anticoagulation encounters.

Drug interactions between ALK inhibitors and warfarin with concurrent use of bucolome: a case report

BackgroundAlectinib, crizotinib, and ceritinib, are anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) that exhibit high protein binding, and their metabolism is associated with the cytochrome P450 (CYP) isoenzymes 2C9 or 3A4. The plasma protein binding rate of warfarin, which is used to prevent and treat venous thromboembolism, is also high. Warfarin is a racemate of S-warfarin and R-warfarin, which are metabolized by CYP2C9 and CYP3A4, respectively. Reports on the drug interactions between each of the above-mentioned ALK-TKIs and warfarin with concurrent use of bucolome are currently lacking.Case presentation.We report a case of a patient receiving warfarin and bucolome, whose international normalized ratio (INR) increased after sequential treatment with alectinib, crizotinib, and ceritinib. The patient was a 61-year-old man with a history of aortic valve regurgitation, who was receiving warfarin treatment following aortic valve replacement. Bucolome, which can enhance the effect of warfarin, was also used simultaneously. The patient was diagnosed with primary lung adenocarcinoma, and ALK rearrangement was detected during second-line chemotherapy. After progression of the disease with chemotherapy, sequential treatment with alectinib, crizotinib, and ceritinib was initiated. Pretreatment INR values were in the therapeutic range (target INR of 2–3) but increased to supratherapeutic levels each time after initiation of alectinib, crizotinib, or ceritinib treatment. Adjustment of warfarin dose or discontinuation of bucolome were necessary to maintain the therapeutic INR range. There were no serious bleeding events or substantial changes in dietary intake.Displacement of plasma protein binding or competitive inhibition of metabolism by alectinib, crizotinib, and ceritinib could increase the plasma concentration of the unbound form of warfarin, resulting in high INR values. In addition, alectinib, crizotinib, and ceritinib might cause displacement of bucolome from plasma proteins, followed by displacement of warfarin or inhibition of warfarin metabolism caused by the unbound form of bucolome.ConclusionsClose monitoring of INR and adjustment of warfarin dosage are needed during treatment with alectinib, crizotinib, or ceritinib in patients who receive warfarin with concurrent use of bucolome.

Contemporary Antiplatelet and Anticoagulant Therapies for Secondary Stroke Prevention: A Narrative Review of Current Literature and Guidelines.

Stroke is a leading cause of death and disability worldwide. The annual incidence of new or recurrent stroke is approximately 795,000 cases per year in the United States, of which 87% are ischemic in nature. In addition to the management of modifiable high-risk factors to reduce the risk of recurrent stroke, antithrombotic agents (antiplatelets and anticoagulants) play an important role in secondary stroke prevention. This review will discuss the published literature on the use of antiplatelets and anticoagulants in secondary prevention of acute ischemic stroke and transient ischemic attack (TIA), including their pharmacology, efficacy, and adverse effects. We will also highlight the role of dual antiplatelet therapy (DAPT) in secondary stroke prevention, along with supporting literature. Single antiplatelet therapy (SAPT) with aspirin or clopidogrel reduces the risk of recurrent ischemic stroke in patients with non-cardioembolic ischemic stroke or TIA. However, as shown in recent trials, short-term DAPT with aspirin and clopidogrel or ticagrelor for 21-30days is more effective than SAPT in patients with minor acute non-cardioembolic stroke or high-risk TIA. Although short-term DAPT is highly effective in preventing recurrent stroke, a more prolonged course can increase bleeding risks without additional benefit. DAPT for 90days, followed by aspirin monotherapy for patients with large vessel intracranial atherosclerotic disease, is suitable for secondary stroke prevention. However, patients need to be monitored for both minor (e.g., bruising) and major (e.g., intracranial) bleeding complications. Conversely, oral warfarin and newer direct oral anticoagulant (DOACs) such as dabigatran, rivaroxaban, apixaban, and edoxaban are the agents of choice for secondary stroke prevention in patients with non-valvular cardioembolic strokes. DOACs may be preferred over warfarin due to decreased bleeding risks, including ICH, lack of need for international normalized ratio monitoring, no dietary restrictions, and limited drug-drug interactions. The choice between different antiplatelets and anticoagulants for prevention of ischemic stroke depends on the underlying stroke mechanism, cytochrome P450 2C19 polymorphisms, bleeding risk profile, compliance, drug tolerance, and drug resistance. Physicians must carefully weigh each patient's relative benefits and bleeding risks before initiating an antiplatelet/anticoagulant treatment regimen. Further studies are warranted to study the optimal duration of DAPT in symptomatic intracranial atherosclerosis since the benefit is most pronounced in the short term while the bleeding risk remains high during the extended duration of therapy.

Pharmacogenetics of warfarin dosing in Chinese adults with nonvalvular atrial fibrillation.

The guide for the use of genotype-guided warfarin dosing in patients for the treatment of non-valvular atrial fibrillation (AF) is still lacking. We aimed to evaluate whether genotype-guided warfarin dosing is superior to conventional clinical dosing for the outcomes of interest in Chinese patients. Our study consisted of 508 newly recruited and 471 existing Chinese AF patients. Among the total 979 patients, 585 patients received their dose of warfarin determined by a genetic and clinical factor (gene group), while the remaining 394 patients whose dosing was determined empirically in control group. We incorporated CYP2C9 and VKORC1 genotypes into the gene group. The international normalized ratio (INR) measurement and standard protocols were used for further dose adjustment in both groups. The primary outcomes were the percentage of time in the therapeutic range (%TTR) and INR during 12-month follow-up. Secondary safety outcome included bleeding and thrombotic events. Compared with the control group, the average TTR of the gene group was higher [68.4 ± 20.6% vs 48.5 ± 21.6%, P < 0.001]. The average INR monitoring times to reach the therapeutic time in the gene group was lower (P < 0.001). The risk ratios (RR) for cumulative incidence of total bleeding events, minor bleeding events, gastrointestinal bleeding, and intracerebral bleeding events were not significantly different between the two groups (P > 0.05). Comparing to the analysis using existing 471 patients, the analysis using total 979 patients showed that the gene group experienced a lower (RR 0.4 (95% CI 0.2 to 0.8), P = 0.008) incidence of cumulative ischemic stroke. Genotype-guided warfarin administration increases the average TTR, reaches higher TTR levels in the early anticoagulant phase, and significantly reduces the risk of ischemic stroke events.

Edoxaban Anticoagulation in Atrial Fibrillation: Real-World Data and Evidence.

Atrial fibrillation (AF) and stroke are two prevalent health conditions with many shared risk factors. Over the past two decades, non-vitamin K antagonist oral anticoagulants (NOACs) have emerged as important alternatives to vitamin K antagonists, owing to their efficacy, safety profile, and the absence of a need for frequent international normalized ratio monitoring. Introduced as the most recent NOAC, edoxaban has been approved for stroke prevention in non-valvular AF in numerous countries since 2014. The pivotal phase III Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial demonstrated that edoxaban is as efficacious as warfarin in preventing strokes and systemic embolic events. Furthermore, it is linked to reduced rates of major, life-threatening, intracranial, major, or clinically relevant non-major bleeding events and decreased cardiovascular mortality in AF when compared to warfarin. Growing data highlights the utilization of edoxaban in treating AF patients in clinical settings. This article provides an overview of real-world evidence regarding edoxaban's use in preventing stroke and systemic embolic events in AF patients, emphasizing the concerns that physicians factor into their clinical decision-making.

Interference in point-of-care international normalized ratio monitoring in patients with lupus anticoagulant is correlated with anti–β2-glycoprotein I antibody titers

BackgroundPatients with antiphospholipid syndrome (APS) receive anticoagulant therapy with vitamin K antagonists (VKAs) to prevent recurrent thrombosis. VKA treatment requires strict monitoring with an international normalized ratio (INR). It is known that lupus anticoagulants (LAs) can lead to elevated INR results with point-of-care-testing (POCT) devices, which could result in inadequate adaptation of anticoagulant therapy. ObjectiveTo determine discrepancies between POCT-INR and laboratory-INR in patients who are LA-positive on VKA therapy. MethodsPaired INR testing was performed with 1 POCT device (CoaguChek XS) and 2 laboratory assays (Owren and Quick method) in 33 patients with LA-positive APS on VKA in a single-center cross-sectional study. Patients were tested for anti–β2-glycoprotein I, anticardiolipin, and antiphosphatidylserine/prothrombin immunoglobulin (Ig) G and IgM antibodies. Agreement between assays was evaluated with Spearman’s correlation, Lin’s correlation coefficient, and Bland–Altman plots. Agreement limits were considered satisfactory if differences were ≤20% as determined by the Clinical and Laboratory Standards Institute. ResultsWe found poor agreement between POCT-INR and laboratory-INR based on Lin’s concordance correlation coefficient (ρc) of 0.42 (95% CI, 0.26-0.55) between POCT-INR and Owren-INR, a ρc of 0.64 (95% CI, 0.47-0.76) between POCT-INR and Quick-INR, and a ρc of 0.77 (95% CI, 0.64-0.85) between Quick-INR and Owren-INR. High anti-β2-glycoprotein I IgG antibody titers correlated with INR disagreement between POCT-INR and laboratory-INR. ConclusionThere is a disagreement between INR values measured with the CoaguChek XS and laboratory-INR in a proportion of patients with LA. Consequently, laboratory-INR monitoring should be preferred over POCT-INR monitoring in patients with LA-positive APS, especially in patients with high anti-β2-glycoprotein IgG antibody titers.

Real-World Comparison of Direct Oral Anticoagulants to Warfarin Among Patients with Atrial Fibrillation/Flutter Managed By an Anticoagulation Service

Introduction: The use of warfarin to prevent ischemic stroke in patients with atrial fibrillation/flutter (AF) requires routine international normalized ratio monitoring and frequent dose adjustments to optimize time in therapeutic range (TTR). While TTR are generally low in usual care, anticoagulation services are associated with improved TTR and clinical outcomes. The direct oral anticoagulants (DOAC) are preferred to warfarin for AF as randomized controlled trial (RCT) data have shown they are as effective in preventing stroke with a lower risk of bleeding, particularly intracranial hemorrhage, compared to warfarin. However, the mean TTR for warfarin-treated patients enrolled in these RCT were relatively modest (55-65%); thus, it is unclear if clinical outcomes would differ if patients in the RCT control groups had been managed by an anticoagulation service. The purpose of this study was to evaluate the real-world effectiveness and safety of DOAC compared to warfarin among patients with AF followed by an anticoagulation service. Methods: This was a retrospective, longitudinal cohort study conducted at Kaiser Permanente Colorado, an integrated healthcare delivery system with a pharmacist-managed anticoagulation service. Adult patients diagnosed with AF, newly initiated on a DOAC or warfarin, and enrolled in the service between 11/01/2015 and 12/31/2018 were followed until anticoagulant switch/discontinuation, a study outcome, membership termination, or 01/05/2019, whichever came first. The index date was the date of service enrollment. TTR and percent of days covered (PDC, a measure of medication adherence) were calculated for the warfarin and DOAC patients, respectively. The primary outcome was a composite of all-cause mortality, clinically-relevant bleeding, ischemic stroke, or systemic embolism. Secondary outcomes included the individual components of the primary outcome as well as follow-up healthcare utilization. Multivariate Cox proportional hazards (reported as adjusted hazard ratio [aHR] with 95% confidence interval [CI]) and negative binomial (reported as adjusted incidence rate ratio [aIRR] with 95% CI) regression analyses were performed to assess differences between groups. All aspects of this study were reviewed and approved by the KPCO Institutional Review Board before data collection. Results: There were 2928 patients included with 1537 and 1391 warfarin and DOAC patients, respectively. The cohort was primarily older, male, and white with moderate burden of chronic disease and baseline healthcare utilization. Warfarin patients had a mean TTR of 72% and were more likely to be female and Medicaid beneficiaries and have had dementia, depression, and pulmonary disease comorbidities (all p<0.05). DOAC patients had a mean PDC of 83% and were more likely to have had a baseline hospitalization (p<0.05). With adjustment for age, sex, Charlson comorbidity index, race, Medicaid status, baseline healthcare utilization, dementia, depression and pulmonary disease comorbidities, patients on a DOAC had an associated lower risk of the primary composite outcome (aHR 0.75, 95% CI 0.62 - 0.91), any clinically-relevant bleeding (aHR 0.68, 95% CI 0.51 - 0.92), gastrointestinal bleeding (aHR 0.62, 95% CI 0.46 - 0.54), systemic embolism (aHR 0.59, 95% CI 0.36 - 0.95), and follow-up hospitalization (aIRR 0.76, 95% CI 0.65 - 0.89) (Table). DOAC patients had equivalent risks of ischemic stroke, all-cause mortality, intracerebral bleeding, and follow-up emergency department visits (all p>0.05). Conclusions: This retrospective analysis of a large sample of real-world patients with AF managed by an anticoagulation service identified that DOAC use was associated with improved safety compared to warfarin. Despite high-quality warfarin management, use of DOAC was associated with lower risks of clinically-relevant bleeding, systemic embolism, and hospitalization compared to patients receiving warfarin for AF which reinforce the application of RCT findings to health systems with available anticoagulation management services. Future real-world studies should be conducted to confirm our findings with multiple healthcare delivery systems, a larger sample size, and assessments of the individual DOAC versus warfarin to provide further evidence of the effectiveness and safety of DOAC. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Potential drug-drug interaction between warfarin and norethindrone in adolescent females: A case series.

In the pediatric population, warfarin remains the recommended oral anticoagulant for valvular heart disease. Warfarin carries a risk of bleeding complications that can manifest as heavy menstrual bleeding (HMB) in postmenarchal adolescent females. As a result, these patients may be started on hormonal therapies, such as norethindrone, to suppress menstruation. This case series describes a potential drug interaction between warfarin and norethindrone in 3 adolescent females with a history of mechanical mitral valve replacement who developed HMB. These patients were on stable warfarin regimens before the initiation of norethindrone and subsequently experienced increases in their international normalized ratio (INR). In response, they required an up to 50% reduction in their weekly warfarin dose over 5 to 12 weeks. These observations suggest that use of norethindrone for the management of HMB may significantly potentiate the anticoagulant effect of warfarin. Close INR monitoring and aggressive dose adjustments during initiation and discontinuation of norethindrone are recommended in patients on warfarin.

Rosendaal linear interpolation method appraising of time in therapeutic range in patients with 12-week follow-up interval after mechanical heart valve replacement.

BackgroundThe objective of this study was to evaluate the quality of anticoagulation by the time in therapeutic range (TTR) for patients with 12-week INR follow-up interval.Materials and methodsFrom January 2018 to December 2020, a selective group of patients who underwent mechanical valve replacement and followed up at our anticoagulation clinic for adjustment of warfarin dose were enrolled. The incidences of complications of anticoagulation therapy were reported by linearized rates. TTR was calculated by the Rosendaal linear interpolation method.ResultsTwo hundred and seventy-four patients were eligible for this study. The mean age of these patients was 52.8 ± 12.7 years, and 65.7% (180 cases) of them were females. The mean duration of warfarin therapy was 16.7 ± 28.1 months. A total of 1309 INR values were collected, representing 66789 patient days. In this study, the mean TTR was 63.7% ± 18.6%, weekly doses of warfarin were 20.6 ± 6.0 mg/weekly, and the mean monitoring interval for the patient was 53.6 ± 27.1 days. There were 153 cases in good TTR group (TTR ≥ 60%) and 121 cases in poor TTR group (TTR < 60%). The calculated mean TTR in both groups was 42.6% ± 22.1% and 74.8% ± 10.4%, respectively. Compared with the TTR ≥ 60% group, the TTR < 60% group exhibited a more prevalence of female gender (p = 0.001), atrial fibrillation (p < 0.001), NYHA ≥ III (p < 0.001), and lower preoperative left ventricular ejection fraction (LVEF, p = 0.032). In multivariate analysis, female gender (p = 0.023) and atrial fibrillation (p = 0.011) were associated with TTR < 60%. The incidence of major bleeding and thromboembolic events was 2.7% and 1.1% patient-years, respectively. There was one death which resulted from cerebral hemorrhage. The incidence of death was 0.5% patient-years. The difference in anticoagulation-related complications between the TTR < 60% group and the TTR ≥ 60% group was not statistically significant.ConclusionFor patients with stable international normalized ratio monitoring results who are follow-up at anticoagulation clinics, a 12-week monitoring interval has an acceptable quality of anticoagulation. The female gender and atrial fibrillation were associated with TTR < 60%.

Impact of pharmacist intervention on anticoagulation management and risk for potential COVID-19 exposure during the COVID-19 pandemic

IntroductionPatients 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 methodsA 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. ResultsAs 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). ConclusionsThis 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.