The year in cardiology: arrhythmias and pacing.

During this last year, there has been much progress with regard to anticoagulant and ablation therapy for atrial fibrillation (AF). Apart from recently issued European Society of Cardiology Guidelines for the management of patients with supraventricular arrhythmias, there has been little progress in research in this field. Ventricular arrhythmias and device therapy have seen modest progress

ASSOCIATION BETWEEN WARFARIN ADHERENCE TRAJECTORIES, HOSPITALIZATION RISK, AND HEALTHCARE UTILIZATION AMONG MEDICARE PATIENTS WITH ATRIAL FIBRILLATION: A GROUP-BASED TRAJECTORY MODELLING APPROACH

Introduction: Warfarin is the most commonly prescribed drug for stroke prevention among Atrial Fibrillation (AF) patients, especially in older adult populations, but medication nonadherence reduces its effectiveness in clinical practice. Group Based Trajectory Models (GBTM) have been used to identify distinct patterns of adherence behavior related to various medications and understand the patient characteristics associated with each trajectory. The objectives of the study were: 1) Describe trajectories of warfarin adherence among Medicare AF patients, 2) Assess impact of adherence trajectories on AF-related hospitalization, 3) Estimate the AF-related direct costs for each adherence trajectory group. Methods: We identified elderly AF patients initiating warfarin treatment during 2008-2010 using data from a random sample of Medicare beneficiaries. The study’s first aim is to classify patients into different trajectory groups based on their monthly adherence patterns using a Group-Based Trajectory Model (GBTM). A multinomial regression model was used to assess associations between baseline characteristics and adherence trajectories. The second aim is to evaluate the association between adherence trajectories and time to first hospitalization related to stroke or bleeding event. Hospitalization events due to bleeding or stroke were identified using corresponding ICD-9 codes, and a Cox proportional hazard model was performed. The third aim of the study is to calculate AF-related direct medical costs associated with each trajectory group. SASv9.4 was used for analysis. Results: Among 3,246 beneficiaries who met inclusion criteria, six adherence trajectories were identified: 1) rapid-decline non-adherence group (11.5%), 2) moderate non-adherence group (24%), 3) rapid-decline then increasing adherence group (6.8%), 4) moderate-decline non-adherence group (8.2%), 5) slow-decline non-adherence group (24.3%), and 6) perfect adherence group (25.3%). Even though no statistical significances were found in the hazard of hospitalization among the adherence groups, there were higher odds of hospitalization among the lower adherence groups compared to perfect adherence group. Outpatient and monitoring costs were significantly higher in the lower adherence trajectories compared to perfect adherence group. Conclusion:The GBTM is considered an innovative methodological approach that can be applied to longitudinal medication adherence data and account for the dynamic nature of adherence behavior in a better way than traditional adherence measures

Prescribers’ perceptions of benefits and limitations of direct acting oral anticoagulants in non-valvular atrial fibrillation.

Background: There is an acknowledged lack of robust and rigorous research focusing on the perspectives of those prescribing direct acting oral anticoagulants (DOACs) for non-valvular atrial fibrillation (AF). Objective: The objective was to describe prescribers’ experiences of using DOACs in the management of non-valvular AF, including perceptions of benefits and limitations. Methods: A cross-sectional survey of prescribers in a remote and rural area of Scotland. Among other items, the questionnaire invited free-text description of positive and negative experiences of DOACs, and benefits and limitations. Responses were independently analysed by two researchers using a summative content analysis approach. This involved counting and comparison, via keywords and content, followed by interpretation and coding of the underlying context into themes. Results: One hundred and fifty-four responses were received, 120 (77.9%) from physicians, 18 (11.7%) from nurse prescribers and 10 (6.4%) from pharmacist prescribers (6 unidentified professions). Not having to monitor INR was the most cited benefit, particularly for prescribers and patients in remote and rural settings, followed by potentially improved patient adherence. These benefits were reflected in respondents’ descriptions of positive experiences and patient feedback. The main limitations were the lack of reversal agents, cost and inability to monitor anticoagulation status. Many described their experiences of adverse effects of DOACs including fatal and non-fatal bleeding, and upper gastrointestinal disturbances. Conclusions: While prescribers have positive experiences and perceive benefits of DOACs, issues such as adverse effects and inability to monitor anticoagulation status merit further monitoring and investigation. These issues are particularly relevant given the trajectory of increased prescribing of DOACs

Making Informed Decisions:the Value of Testing Strategies in Healthcare

In this thesis, I cover many aspects related to the economics of testing strategies in healthcare, from the organization of screening tests to the use of diagnostics to combat antimicrobial resistance. It is important to consider the testing infrastructure: where should testing take place, close to the patient or in specialized laboratories; who should perform the test and how are these health professionals organized; and what value do the test results have for public health and how are these data shared? These are some of the issues to be considered when deciding when to implement or reimburse tests. From a cost-effectiveness perspective, the underlying clinical data should be sufficient to compare the testing strategy to other health technologies, by using generalizable health outcomes, such as quality-adjusted life years, and by using sufficiently long time hori¬zons. In a cost-effectiveness analysis, the costs for society are related to the clinical benefits for patients, but for microbiological tests, the clinical value is broader than that, especially if tests can identify specific pathogens. The collected data can be used to make public health decisions, for example by updating treatment guidelines for infectious disease and by responding to antimicrobial resistance and potentially pandemic pathogens

Anticoagulant Use, Safety and Effectiveness for Ischemic Stroke Prevention in Nursing Home Residents with Atrial Fibrillation

Background Fewer than one-third of nursing home residents with atrial fibrillation were treated with the only available oral anticoagulant, warfarin, historically. Management of atrial fibrillation has transformed in recent years with the approval of 4 direct-acting oral anticoagulants (DOACs) since 2010. Methods Using the national Minimum Data Set 3.0 linked to Medicare Part A and D claims, we first described contemporary (2011-2016) warfarin and DOAC utilization in the nursing home population (Aim 1). In Aim 2, we linked residents to nursing home and county level data to study associations between resident, facility, county, and state characteristics and anticoagulant treatment. Using a new-user active comparator design, we then compared the incidence of safety (i.e., bleeding), effectiveness (i.e., ischemic stroke), and mortality outcomes between residents initiating DOACs versus warfarin (Aim 3). Results The proportion of residents with atrial fibrillation receiving treatment increased from 42.3% in 2011 to 47.8% as of December 31, 2016, at which time 48.2% of treated residents received DOACs. Demographic and clinical characteristics of residents using DOACs and warfarin were similar in 2016. Half of the 8,734 DOAC users received standard dosages and most were treated with apixaban (54.4%) or rivaroxaban (35.8%) in 2016. Compared with warfarin, bleeding rates were lower and ischemic stroke rates were higher for apixaban users. Ischemic stroke and bleeding rates for dabigatran and rivaroxaban were comparable to warfarin. Mortality rates were lower versus warfarin for each DOAC. Conclusions In nursing homes, DOACs are being used commonly and with equal or greater benefit than warfarin

Doctor of Philosophy

dissertationAtrial fibrillation (AF) is the most common clinical arrhythmia, posing a major risk for occurrence of ischemic stroke. Oral anticoagulation and antiplatelet agents are used to prevent stroke. One major complication related to these therapies is the development of a hemorrhage. Providers are faced with treating older adults with AF who have concomitant geriatric syndromes that potentially alter treatment outcomes. This study involved examining records of subjects age ≥ 65 diagnosed with AF and concomitant geriatric syndromes (dementia, frailty, and/or falls) to describe differences in incidence of strokes and hemorrhages, depending upon the type of prevention therapy, and differences in incidences of stroke in patients with and without geriatric syndromes. Older adult patients with geriatric syndromes were divided into three groups based on the type of antithrombotic therapy prescribed at diagnosis of AF: oral anticoagulation, antiplatelet agents, or no oral anticoagulants or antiplatelet agents, with primary outcomes of a stroke or hemorrhage. In a separate analysis, older adults with and without geriatric syndromes across the three therapy groups were compared with primary outcome for stroke. Multivariable Cox hazard, logistic regression, and Kaplan Meier survival curves were utilized to determine association of treatment with risk-adjusted stroke and hemorrhage incidence. Compared to patients prescribed no antithrombotic therapy, the reduced stroke occurrence was 75% to 82% oral anticoagulants and 70% to 74% in those prescribed iv antiplatelet agents (both p < .001), after controlling for risk. Patients prescribed antiplatelet agents and oral anticoagulants were 3.28 and 3.19 times more likely, respectively, than patients not prescribed antithrombotics to develop noncranial hemorrhage (p < .05). Patients with geriatric syndromes experienced higher incidence of stroke when prescribed oral anticoagulants (p = 0.00) and antiplatelet agents (p < 0.001), compared to patients without geriatric syndromes. Subjects with geriatric syndromes had benefit and risk profiles when prescribed oral anticoagulant and antiplatelet therapies to prevent thromboembolism similar to other populations recorded, although overall stroke incidence was greater. This suggests that populations with geriatric syndromes should be specifically incorporated into the guidelines clinicians use to tailor antithrombotic therapies to individual patient risk

Assessment of an Intervention to Reduce Aspirin Prescribing for Patients Receiving Warfarin for Anticoagulation

Importance: For some patients receiving warfarin, adding aspirin (acetylsalicylic acid) increases bleeding risk with unclear treatment benefit. Reducing excess aspirin use could be associated with improved clinical outcomes. Objective: To assess changes in aspirin use, bleeding, and thrombosis event rates among patients treated with warfarin. Design, Setting, and Participants: This pre-post observational quality improvement study was conducted from January 1, 2010, to December 31, 2019, at a 6-center quality improvement collaborative in Michigan among 6738 adults taking warfarin for atrial fibrillation and/or venous thromboembolism without an apparent indication for concomitant aspirin. Statistical analysis was conducted from November 26, 2020, to June 14, 2021. Intervention: Primary care professionals for patients taking aspirin were asked whether an ongoing combination aspirin and warfarin treatment was indicated. If not, then aspirin was discontinued with the approval of the managing clinician. Main Outcomes and Measures: Outcomes were assessed before and after intervention for the primary analysis and before and after 24 months before the intervention (when rates of aspirin use first began to decrease) for the secondary analysis. Outcomes included the rate of aspirin use, bleeding, and thrombotic outcomes. An interrupted time series analysis assessed cumulative monthly event rates over time. Results: A total of 6738 patients treated with warfarin (3160 men [46.9%]; mean [SD] age, 62.8 [16.2] years) were followed up for a median of 6.7 months (IQR, 3.2-19.3 months). Aspirin use decreased slightly from a baseline mean use of 29.4% (95% CI, 28.9%-29.9%) to 27.1% (95% CI, 26.1%-28.0%) during the 24 months before the intervention (P \u3c .001 for slope before and after 24 months before the intervention) with an accelerated decrease after the intervention (mean aspirin use, 15.7%; 95% CI, 14.8%-16.8%; P = .001 for slope before and after intervention). In the primary analysis, the intervention was associated with a significant decrease in major bleeding events per month (preintervention, 0.31%; 95% CI, 0.27%-0.34%; postintervention, 0.21%; 95% CI, 0.14%-0.28%; P = .03 for difference in slope before and after intervention). No change was observed in mean percentage of patients having a thrombotic event from before to after the intervention (0.21% vs 0.24%; P = .34 for difference in slope). In the secondary analysis, reducing aspirin use (starting 24 months before the intervention) was associated with decreases in mean percentage of patients having any bleeding event (2.3% vs 1.5%; P = .02 for change in slope before and after 24 months before the intervention), mean percentage of patients having a major bleeding event (0.31% vs 0.25%; P = .001 for change in slope before and after 24 months before the intervention), and mean percentage of patients with an emergency department visit for bleeding (0.99% vs 0.67%; P = .04 for change in slope before and after 24 months before the intervention), with no change in mean percentage of patients with a thrombotic event (0.20% vs 0.23%; P = .36 for change in slope before and after 24 months before the intervention). Conclusions and Relevance: This quality improvement intervention was associated with an acceleration of a preexisting decrease in aspirin use among patients taking warfarin for atrial fibrillation and/or venous thromboembolism without a clear indication for aspirin therapy. Reductions in aspirin use were associated with reduced bleeding. This study suggests that an anticoagulation clinic-based aspirin deimplementation intervention can improve guideline-concordant aspirin use

Chronic kidney disease and arrhythmias: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.

Patients with chronic kidney disease (CKD) are predisposed to heart rhythm disorders, including atrial fibrillation (AF)/atrial flutter, supraventricular tachycardias, ventricular arrhythmias, and sudden cardiac death (SCD). While treatment options, including drug, device, and procedural therapies, are available, their use in the setting of CKD is complex and limited. Patients with CKD and end-stage kidney disease (ESKD) have historically been under-represented or excluded from randomized trials of arrhythmia treatment strategies,1 although this situation is changing.2 Cardiovascular society consensus documents have recently identified evidence gaps for treating patients with CKD and heart rhythm disorders [...

Personalised approaches to antithrombotic therapies: insights from linked electronic health records

Antithrombotic drugs are increasingly used for the prevention of atherothrombotic events in cardiovascular diseases and represent a paradigm for the study of personalised medicine because of the need to balance potential benefits with the substantial risks of bleeding harms. To be effective, personalised medicine needs validated prognostic risk models, rich phenotypes, and patient monitoring over time. The opportunity to use linked electronic health records has potential advantages; we have rich longitudinal data spanning patients’ entire journey through the healthcare system including primary care visits, clinical biomarkers, hospital admissions, hospital procedures and prescribed medication. Challenges include structuring the data into research-ready format and accurately defining clinical endpoints and handling missing data. The data used in this thesis was from the CALIBER platform: linked routinely-collected electronic health records from general practices, hospitals admissions, myocardial infarction registry and death registry for 2 million patients in England from 1997 to 2010. In this thesis I (1) developed comprehensive bleeding phenotypes in linked electronic health records, (2) assessed the incidence and prognosis of bleeding in atrial fibrillation and coronary disease patients in England, (3) developed and validated prognostic models for atherothrombotic and bleeding events in stable myocardial infarction survivors pertaining to the benefits and harms of prolonged dual antiplatelet therapy, (4) assessed the predictors and outcomes associated with time in therapeutic range for patients treated with oral anticoagulants (5) assessed the predictive value of novel measures of international normalised ratio control in patients treated with oral anticoagulants for atherothrombotic and bleeding outcomes. Taken together these findings offer researchers scalable methodological approaches, that may be applied to other diseases and treatments with crucial benefits and harms considerations, and demonstrates how records used in clinical practice maybe harnessed to improve treatment decisions, monitoring and overall care of a cardiovascular disease population treated with a class of drugs