Antiplatelet Agents and Oral Anticoagulant Use in Patients with Atrial Fibrillation and Carotid Artery Disease After First-Time Ischaemic Stroke.

INTRODUCTION: People with atrial fibrillation (AF) frequently have competing mechanisms for ischaemic stroke, including extracranial carotid atherosclerosis. The objective of this study was to determine associations between use of oral anticoagulants (OACs) plus antiplatelet agents (APA) after ischaemic stroke and outcomes for patients with AF and carotid artery disease. PATIENTS AND METHODS: A retrospective cohort study was conducted. Participants receiving OACs with or without APA were propensity score-matched for age, sex, ethnicity, co-morbidities and presence of cardiac and vascular implants and grafts. Outcomes were 1-year mortality, recurrent stroke and major bleeding. RESULTS: Of 5708 patients, 24.1% (n=1628) received non-vitamin K antagonist OACs (NOACs) with no APA, 26.0% (n=1401) received NOACs plus APA, 20.7% (n=1243) received warfarin without APA and 29.2% (n=1436) received warfarin plus APA. There was no significant difference in risk of recurrent stroke between the groups. Compared to receiving NOACs without APA, receiving warfarin plus APA was associated with a higher risk of mortality (hazard ratio (HR) 1.51 (95% confidence interval (CI) 1.20, 1.89)) and major bleeding (HR 1.66 (95% CI 1.40, 1.96)). Receiving NOACs plus APA was also associated with a higher risk of major bleeding compared to NOACs without APA (HR 1.27 (95% CI 1.07, 1.51), respectively). CONCLUSIONS: The results suggest for patients with AF and carotid artery disease after ischaemic stroke, receiving NOACs without APA is associated with a lower risk of major bleeding with no negative impact on recurrent stroke or mortality. Evidence from randomised trials is needed to confirm this finding.

Assessing medical product safety during pregnancy using parameterizable tools in the sentinel distributed database.

PURPOSE: The US Food and Drug Administration established the Sentinel System to monitor the safety of medical products. A component of this system includes parameterizable analytic tools to identify mother-infant pairs and evaluate infant outcomes to enable the routine monitoring of the utilization and safety of drugs used in pregnancy. We assessed the feasibility of using the data and tools in the Sentinel System by assessing a known association between topiramate use during pregnancy and oral clefts in the infant. METHODS: We identified mother-infant pairs using the mother-infant linkage table from six data partners contributing to the Sentinel Distributed Database from January 1, 2000, to September 30, 2015. We compared mother-infant pairs with first-trimester exposure to topiramate to mother-infant pairs that were topiramate-unexposed or lamotrigine-exposed and used a validated algorithm to identify oral clefts in the infant. We estimated adjusted risk ratios through propensity score stratification. RESULTS: There were 2007 topiramate-exposed and 1 066 086 unexposed mother-infant pairs in the main comparison. In the active-comparator analysis, there were 1996 topiramate-exposed and 2859 lamotrigine-exposed mother-infant pairs. After propensity score stratification, the odds ratio for oral clefts was 2.92 (95% CI: 1.43, 5.93) comparing the topiramate-exposed to unexposed groups and 2.72 (95% CI: 0.75, 9.93) comparing the topiramate-exposed to lamotrigine-exposed groups. CONCLUSIONS: We found an increased risk of oral clefts after topiramate exposure in the first trimester in the Sentinel database. These results are similar to prior published observational study results and demonstrate the ability of Sentinel's data and analytic tools to assess medical product safety in cohorts of mother-infant pairs in a timely manner.

Exercise-Based Cardiac Rehabilitation Associates with Lower Major Adverse Cardiovascular Events in People with Stroke.

BACKGROUND: The risk of major adverse cardiovascular events is substantially increased following a stroke. Although exercise-based cardiac rehabilitation has been shown to improve prognosis following cardiac events, it is not part of routine care for people following a stroke. We therefore investigated the association between cardiac rehabilitation and major adverse cardiovascular events for people with stroke. METHODS: This retrospective analysis was conducted on June 20, 2021, using anonymized data within TriNetX, a global federated health research network with access to electronic medical records from participating healthcare organizations, predominantly in the USA. All participants were aged ≥18 years with cerebrovascular disease and at least 2 years of follow-up. People with stroke and an electronic medical record of exercise-based cardiac rehabilitation were 1:1 propensity score matched to people with stroke but without cardiac rehabilitation using participant characteristics, comorbidities, cardiovascular procedures, and cardiovascular medications. RESULTS: Of 836,923 people with stroke and 2-year follow-up, 2,909 met the inclusion for the exercise-based cardiac rehabilitation cohort. Following propensity score matching (n = 5,818), exercise-based cardiac rehabilitation associated with 53% lower odds of all-cause mortality (odds ratio 0.47, 95% confidence interval: 0.40-0.56), 12% lower odds of recurrent stroke (0.88, 0.79-0.98), and 36% lower odds of rehospitalization (0.64, 0.58-0.71), compared to controls. No significant association between cardiac rehabilitation and incident atrial fibrillation was observed. CONCLUSION: Exercise-based cardiac rehabilitation prescribed for people following a stroke associated with significantly lower odds of major adverse cardiovascular events at 2 years, compared to usual care.

Utility of fertility procedures and prenatal tests to estimate gestational age for live-births and stillbirths in electronic health plan databases.

PURPOSE: Current algorithms to evaluate gestational age (GA) during pregnancy rely on hospital coding at delivery and are not applicable to non-live births. We developed an algorithm using fertility procedures and fertility tests, without relying on delivery coding, to develop a novel GA algorithm in live-births and stillbirths. METHODS: Three pregnancy cohorts were identified from 16 health-plans in the Sentinel System: 1) hospital admissions for live-birth, 2) hospital admissions for stillbirth, and 3) medical chart-confirmed stillbirths. Fertility procedures and prenatal tests, recommended within specific GA windows were evaluated for inclusion in our GA algorithm. Our GA algorithm was developed against a validated delivery-based GA algorithm in live-births, implemented within a sample of chart-confirmed stillbirths, and compared to national estimates of GA at stillbirth. RESULTS: Our algorithm, including fertility procedures and 11 prenatal tests, assigned a GA at delivery to 97.9% of live-births and 92.6% of stillbirths. For live-births (n = 4 701 207), it estimated GA within 2 weeks of a reference delivery-based GA algorithm in 82.5% of pregnancies, with a mean difference of 3.7 days. In chart-confirmed stillbirths (n = 49), it estimated GA within 2 weeks of the clinically recorded GA at delivery for 80% of pregnancies, with a mean difference of 11.1 days. Implementation of the algorithm in a cohort of stillbirths (n = 40 484) had an increased percentage of deliveries after 36 weeks compared to national estimates. CONCLUSIONS: In a population of primarily commercially-insured pregnant women, fertility procedures and prenatal tests can estimate GA with sufficient sensitivity and accuracy for utility in pregnancy studies.

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases.

BACKGROUND: It remains uncertain if prior use of oral anticoagulants (OACs) in COVID-19 outpatients with multimorbidity impacts prognosis, especially if cardiometabolic diseases are present. Clinical outcomes 30-days after COVID-19 diagnosis were compared between outpatients with cardiometabolic disease receiving vitamin K antagonist (VKA) or direct-acting OAC (DOAC) therapy at time of COVID-19 diagnosis. METHODS: A study was conducted using TriNetX, a global federated health research network. Adult outpatients with cardiometabolic disease (i.e. diabetes mellitus and any disease of the circulatory system) treated with VKAs or DOACs at time of COVID-19 diagnosis between 20-Jan-2020 and 15-Feb-2021 were included. Propensity score matching (PSM) was used to balance cohorts receiving VKAs and DOACs. The primary outcomes were all-cause mortality, intensive care unit (ICU) admission/mechanical ventilation (MV) necessity, intracranial haemorrhage (ICH)/gastrointestinal bleeding, and the composite of any arterial or venous thrombotic event(s) at 30-days after COVID-19 diagnosis. RESULTS: 2275 patients were included. After PSM, 1270 patients remained in the study (635 on VKAs; 635 on DOACs). VKA-treated patients had similar risks and 30-day event-free survival than patients on DOACs regarding all-cause mortality, ICU admission/MV necessity, and ICH/gastrointestinal bleeding. The risk of any arterial or venous thrombotic event was 43% higher in the VKA cohort (hazard ratio 1.43, 95% confidence interval 1.03-1.98; Log-Rank test p = 0.029). CONCLUSION: In COVID-19 outpatients with cardiometabolic diseases, prior use of DOAC therapy compared to VKA therapy at the time of COVID-19 diagnosis demonstrated lower risk of arterial or venous thrombotic outcomes, without increasing the risk of bleeding.

Prevalence and clinical outcomes of myocarditis and pericarditis in 718,365 COVID-19 patients.

BACKGROUND: COVID-19 has a wide spectrum of cardiovascular sequelae including myocarditis and pericarditis; however, the prevalence and clinical impact are unclear. We investigated the prevalence of new-onset myocarditis/pericarditis and associated adverse cardiovascular events in patients with COVID-19. METHODS AND RESULTS: A retrospective cohort study was conducted using electronic medical records from a global federated health research network. Patients were included based on a diagnosis of COVID-19 and new-onset myocarditis or pericarditis. Patients with COVID-19 and myocarditis/pericarditis were 1:1 propensity score matched for age, sex, race and comorbidities to patients with COVID-19 but without myocarditis/pericarditis. The outcomes of interest were 6-month all-cause mortality, hospitalisation, cardiac arrest, incident heart failure, incident atrial fibrillation and acute myocardial infarction, comparing patients with and without myocarditis/pericarditis. Of 718,365 patients with COVID-19, 35,820 (5.0%) developed new-onset myocarditis and 10,706 (1.5%) developed new-onset pericarditis. Six-month all-cause mortality was 3.9% (n = 702) in patients with myocarditis and 2.9% (n = 523) in matched controls (p < .0001), odds ratio 1.36 (95% confidence interval (CI): 1.21-1.53). Six-month all-cause mortality was 15.5% (n = 816) for pericarditis and 6.7% (n = 356) in matched controls (p < .0001), odds ratio 2.55 (95% CI: 2.24-2.91). Receiving critical care was associated with significantly higher odds of mortality for patients with myocarditis and pericarditis. Patients with pericarditis seemed to associate with more new-onset cardiovascular sequelae than those with myocarditis. This finding was consistent when looking at pre-COVID-19 data with pneumonia patients. CONCLUSIONS: Patients with COVID-19 who present with myocarditis/pericarditis associate with increased odds of major adverse events and new-onset cardiovascular sequelae.

Higher Mortality of Ischaemic Stroke Patients Hospitalized with COVID-19 Compared to Historical Controls.

INTRODUCTION: Increasing evidence suggests patients with coronavirus disease 2019 (COVID-19) may develop thrombosis and thrombosis-related complications. Some previous evidence has suggested COVID-19-associated strokes are more severe with worse outcomes for patients, but further studies are needed to confirm these findings. The aim of this study was to determine the association between COVID-19 and mortality for patients with ischaemic stroke in a large multicentre study. METHODS: A retrospective cohort study was conducted using electronic medical records of inpatients from 50 healthcare organizations, predominately from the USA. Patients with ischaemic stroke within 30 days of COVID-19 were identified. COVID-19 was determined from diagnosis codes or a positive test result identified with CO-VID-19-specific laboratory codes between January 20, 2020, and October 1, 2020. Historical controls with ischaemic stroke without COVID-19 were identified in the period January 20, 2019, to October 1, 2019. 1:1 propensity score matching was used to balance the cohorts with and without CO-VID-19 on characteristics including age, sex, race and comorbidities. Kaplan-Meier survival curves for all-cause 60-day mortality by COVID-19 status were produced. RESULTS: During the study period, there were 954 inpatients with ischaemic stroke and COVID-19. During the same time period in 2019, there were 48,363 inpatients with ischaemic stroke without COVID-19 (historical controls). Compared to patients with ischaemic stroke without COVID-19, patients with ischaemic stroke and COVID-19 had a lower mean age, had a lower prevalence of white patients, a higher prevalence of black or African American patients and a higher prevalence of hypertension, previous cerebrovascular disease, diabetes mellitus, ischaemic heart disease, atrial fibrillation, chronic kidney disease, chronic obstructive pulmonary disease, liver disease, neoplasms, and mental disorders due to known physiological conditions. After propensity score matching, there were 952 cases and 952 historical controls; cases and historical controls were better balanced on all included characteristics (all p > 0.05). After propensity score matching, Kaplan-Meier survival analysis showed the survival probability was significantly lower in ischaemic stroke patients with COVID-19 (78.3% vs. 91.0%, log-rank test p < 0.0001). The odds of 60-day mortality were significantly higher for patients with ischaemic stroke and COVID-19 compared to the propensity score-matched historical controls (odds ratio: 2.51 [95% confidence interval 1.88-3.34]). DISCUSSION/CONCLUSIONS: Ischaemic stroke patients with COVID-19 had significantly higher 60-day all-cause mortality compared to propensity score-matched historical controls (ischaemic stroke patients without COVID-19).

Validation of an ICD-10-based algorithm to identify stillbirth in the Sentinel System.

PURPOSE: To develop and validate an International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM)-based algorithm to identify cases of stillbirth using electronic healthcare data. METHODS: We conducted a retrospective study using claims data from three Data Partners (healthcare systems and insurers) in the Sentinel Distributed Database. Algorithms were developed using ICD-10-CM diagnosis codes to identify potential stillbirths among females aged 12-55 years between July 2016 and June 2018. A random sample of medical charts (N = 169) was identified for chart abstraction and adjudication. Two physician adjudicators reviewed potential cases to determine whether a stillbirth event was definite/probable, the date of the event, and the gestational age at delivery. Positive predictive values (PPVs) were calculated for the algorithms. Among confirmed cases, agreement between the claims data and medical charts was determined for the outcome date and gestational age at stillbirth. RESULTS: Of the 110 potential cases identified, adjudicators determined that 54 were stillbirth events. Criteria for the algorithm with the highest PPV (82.5%; 95% CI, 70.9%-91.0%) included the presence of a diagnosis code indicating gestational age ≥20 weeks and occurrence of either >1 stillbirth-related code or no other pregnancy outcome code (i.e., livebirth, spontaneous abortion, induced abortion) recorded on the index date. We found ≥90% agreement within 7 days between the claims data and medical charts for both the outcome date and gestational age at stillbirth. CONCLUSIONS: Our results suggest that electronic healthcare data may be useful for signal detection of medical product exposures potentially associated with stillbirth.

Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: A federated electronic medical record analysis.

BACKGROUND: At the beginning of June 2020, there were nearly 7 million reported cases of coronavirus disease 2019 (COVID-19) worldwide and over 400,000 deaths in people with COVID-19. The objective of this study was to determine associations between comorbidities listed in the Charlson comorbidity index and mortality among patients in the United States with COVID-19. METHODS AND FINDINGS: A retrospective cohort study of adults with COVID-19 from 24 healthcare organizations in the US was conducted. The study included adults aged 18-90 years with COVID-19 coded in their electronic medical records between January 20, 2020, and May 26, 2020. Results were also stratified by age groups (<50 years, 50-69 years, or 70-90 years). A total of 31,461 patients were included. Median age was 50 years (interquartile range [IQR], 35-63) and 54.5% (n = 17,155) were female. The most common comorbidities listed in the Charlson comorbidity index were chronic pulmonary disease (17.5%, n = 5,513) and diabetes mellitus (15.0%, n = 4,710). Multivariate logistic regression analyses showed older age (odds ratio [OR] per year 1.06; 95% confidence interval [CI] 1.06-1.07; p < 0.001), male sex (OR 1.75; 95% CI 1.55-1.98; p < 0.001), being black or African American compared to white (OR 1.50; 95% CI 1.31-1.71; p < 0.001), myocardial infarction (OR 1.97; 95% CI 1.64-2.35; p < 0.001), congestive heart failure (OR 1.42; 95% CI 1.21-1.67; p < 0.001), dementia (OR 1.29; 95% CI 1.07-1.56; p = 0.008), chronic pulmonary disease (OR 1.24; 95% CI 1.08-1.43; p = 0.003), mild liver disease (OR 1.26; 95% CI 1.00-1.59; p = 0.046), moderate/severe liver disease (OR 2.62; 95% CI 1.53-4.47; p < 0.001), renal disease (OR 2.13; 95% CI 1.84-2.46; p < 0.001), and metastatic solid tumor (OR 1.70; 95% CI 1.19-2.43; p = 0.004) were associated with higher odds of mortality with COVID-19. Older age, male sex, and being black or African American (compared to being white) remained significantly associated with higher odds of death in age-stratified analyses. There were differences in which comorbidities were significantly associated with mortality between age groups. Limitations include that the data were collected from the healthcare organization electronic medical record databases and some comorbidities may be underreported and ethnicity was unknown for 24% of participants. Deaths during an inpatient or outpatient visit at the participating healthcare organizations were recorded; however, deaths occurring outside of the hospital setting are not well captured. CONCLUSIONS: Identifying patient characteristics and conditions associated with mortality with COVID-19 is important for hypothesis generating for clinical trials and to develop targeted intervention strategies.

Understanding utilization patterns of biologics and biosimilars in the United States to support postmarketing studies of safety and effectiveness.

PURPOSE: To describe utilization of filgrastim and infliximab, the first two products with biosimilars approved in the United States. METHODS: We identified use of filgrastim (reference, tbo-filgrastim, and filgrastim-sndz) and infliximab (reference, infliximab-dyyb, and infliximab-abda) in the Sentinel Distributed Database using Healthcare Common Procedure Coding System (HCPCS) codes and National Drug Codes (NDCs) from January 2015 to August 2018. We calculated the proportion of use by code type and assessed uptake over time. We compared baseline patient characteristics and treatment indications. Among patients with >1 exposure episode, we characterized gaps between episodes. RESULTS: Use was identified primarily via HCPCS codes (filgrastim: 86.4%-97.7%; infliximab: 87.8%-100%) although some was identified via NDCs (filgrastim: 2.2%-13.5%; infliximab: <0.1%-6.5%). Filgrastim reference product use declined from 89.4% in January 2015 to 30.3% in June 2018, with corresponding increases in filgrastim-sndz (0% to 49.3%) and tbo-filgrastim (10.6% to 20.4%). Infliximab biosimilar uptake was low (9.7% in June 2018). We identified 94 846 filgrastim reference product, 27 143 tbo-filgrastim, and 38 264 filgrastim-sndz users. For infliximab, we identified 125 412 reference product, 1034 infliximab-dyyb, 49 infliximab-abda, and 4855 undetermined biosimilar users. Patients receiving filgrastim products were largely similar, but differences in age, sex, and indication were observed across infliximab product users. The median exposure episode gap ranged from 1 to 3 days for filgrastim and 48 to 50 days for infliximab. CONCLUSION: Use of biosimilar filgrastim has increased in the United States, but infliximab biosimilar use remains low. Data on identification of biosimilars in claims data and observed gaps between exposure episodes can be used to support drug safety studies of biosimilars.

First-Trimester Exposure to Gadolinium-based Contrast Agents: A Utilization Study of 4.6 Million U.S. Pregnancies.

BackgroundThe safety of gadolinium-based contrast agent (GBCA) exposure during pregnancy has not been established, and the use of GBCAs during pregnancy is not recommended unless it is essential to the health of the woman or fetus.PurposeTo examine the prevalence of GBCA exposure in a large sample of pregnancies resulting in a live birth.Materials and MethodsThe Sentinel Distributed Database was used to retrospectively identify U.S. pregnancies that resulted in live births between 2006 and 2017 from 16 data partners. The main outcome was the prevalence of MRI procedures with and without GBCAs, sorted by anatomic location and trimester, among pregnant and matched comparator women.ResultsAmong 4 692 744 pregnancies resulting in a live birth, we identified 6879 exposures to GBCAs in 5457 pregnancies, representing one contrast-enhanced MRI examination per 860 pregnancies (0.12% of all pregnancies). Most contrast-enhanced MRI examinations were performed in the head (n = 3499), although pelvic and abdominal MRI constituted 22.3% (n = 1536) of all contrast-enhanced MRI examinations during pregnancy. The majority (70.2%) of GBCA exposures occurred during the first trimester, with a 4.3-fold greater prevalence compared with that in the second trimester and a 5.1-fold greater prevalence compared with that in the third trimester.ConclusionThis study identified higher rates of gadolinium-based contrast agent (GBCA) exposure during the first few weeks of pregnancy compared with the later weeks of pregnancy, suggesting inadvertent exposure to GBCAs might occur before pregnancy is recognized.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Kallmes and Watson in this issue.

A new analytic tool developed to assess safe use recommendations.

PURPOSE: Develop a flexible analytic tool for the Food and Drug Administration's (FDA's) Sentinel System to assess adherence to safe use recommendations with two capabilities: characterize adherence to patient monitoring recommendations for a drug, and characterize concomitant medication use before, during, and/or after drug therapy. METHODS: We applied the tool in the Sentinel Distributed Database to assess adherence to the labeled recommendation that patients treated with dronedarone undergo electrocardiogram (ECG) testing no less often than every 3 months. Measures of length of treatment, time to first ECG, number of ECGs, and time between ECGs were assessed. We also assessed concomitant use of contraception among female users of mycophenolate per label recommendations (concomitancy 4 weeks before through 6 weeks after discontinuation of mycophenolate). Unadjusted results were stratified by age, month-year, and sex. RESULTS: We identified 21 457 new episodes of dronedarone use of greater than or equal to 90 days (July 2009 to September 2015); 86% had greater than or equal to one ECG, and 22% met the recommendation of an ECG no less often than every 3 months. We identified 21 942 new episodes of mycophenolate use among females 12 to 55 years (January 2016 to September 2015); 16% had greater than or equal to 1 day of concomitant contraception dispensed, 12% had concomitant contraception use for greater than or equal to 50% of the 4 weeks before initiation through 6 weeks after mycophenolate; younger females had more concomitancy. These results may be underestimates as the analyses are limited to claims data. CONCLUSIONS: We developed a tool for use in databases formatted to the Sentinel Common Data Model that can assess adherence to safe use recommendations involving patient monitoring and concomitant drug use over time.

Exercised-based cardiac rehabilitation associates with lower all-cause mortality in patients with primary pulmonary hypertension.

Background: Despite pharmacological therapies to improve outcomes of pulmonary hypertension (PH), poor long-term survival remains. Exercised-based cardiac rehabilitation (ExCR) may be an alternative strategy to improve prognosis. Therefore, using an electronic medical record (EMR) database, the objective of this study was to compare mortality between patients with primary PH with ExCR vs. propensity-matched PH patients without ExCR. Methods: The retrospective analysis was conducted on February 15, 2023 using anonymized data within TriNetX, a global federated health research network. All patients were aged ≥18 years with primary PH recorded in EMRs with at least 1-year follow-up from ExCR. Using logistic regression models, patients with PH with an EMR of ExCR were 1:1 propensity score-matched with PH patients without ExCR for age, sex, race, and comorbidities, and cardiovascular care. Results: In total, 109,736 patients with primary PH met the inclusion criteria for the control group and 784 patients with primary PH met the inclusion criteria for the ExCR cohort. Using the propensity score-matched cohorts, 1-year mortality from ExCR was proportionally lower with 13.6% (n = 101 of 744 patients) in the ExCR cohort compared to 23.3% (n = 174 of 747 patients) in the controls (OR 0.52, 95% CI 0.40-0.68). Conclusion: The present study of 1,514 patients with primary PH suggests that ExCR is associated with 48% lower odds of 1-year mortality, when compared to propensity score-matched patients without ExCR.

Evolving Effect of the COVID-19 Pandemic on Cancer-Related Encounters.

PURPOSE: This is an update to a previously published report characterizing the impact that efforts to control the COVID-19 pandemic have had on the normal course of cancer-related encounters. METHODS: Data were analyzed from 22 US health care organizations (members of the TriNetX global network) having relevant, up-to-date encounter data. Although the original study compared encounter data pre-COVID-19 (January-April 2019) with the corresponding months in 2020, this update considers data through April 2021. As before, cohorts were generated for all neoplasm patients (malignant, benign, in situ, and of unspecified behavior), all new incidence neoplasm patients, exclusively malignant neoplasm patients, and new incidence malignant neoplasm patients. Data on the initial cancer stage were available for calendar year 2020 from about one third of the study's organizations. RESULTS: Although COVID-19 cases fluctuated through 2021, newly diagnosed cancers closely paralleled the prepandemic base year 2019. Similarly, screening for breast, colorectal, and cervical cancers quickly recovered beginning in May 2020 to prepandemic numbers. Preliminary data for the initial cancer stage showed no significant difference (P > .10) in distribution for breast or colon cancers between 2019 and 2020. CONCLUSION: Although the number of COVID-19 cases fluctuated, the steep declines observed during March and April 2020 in screening for breast and colon cancer and patients with newly diagnosed cancer did not continue through the rest of 2020 and into April 2021. Screening and new incidence cancer numbers quickly rose compared with prepandemic levels. The concern that more patients with advanced-stage cancer would be seen in the months following the drastic dips of March-April 2020 was not realized as the major disruption to normal cancer care was limited to these 2 months.

Outcomes of left atrial appendage occlusion vs. non-vitamin K antagonist oral anticoagulants in atrial fibrillation.

BACKGROUND: The effects of left atrial appendage (LAA) occlusion compared to non-vitamin K antagonist oral anticoagulant (NOAC) therapy in patients with atrial fibrillation (AF) remain unknown. AIMS: We aimed to evaluate the outcomes in patients with AF who received LAA occlusion vs. NOAC therapy. METHODS: We utilised data from TriNetX which is a global federated health research network currently containing data for 88.5 million patients. ICD-10 codes were employed to identify AF patients treated with either LAA occlusion or NOAC between 1st December 2010 and 17th January 2019. Clinical outcomes of interest were analysed up to 2 years. RESULTS: 108,697 patients were included. Patients who underwent LAA occlusion were younger, more likely to be white Caucasian and male, had a greater incidence of comorbidities, and were less likely to be prescribed other cardiovascular medications. Using propensity score matching, the risk of all-cause mortality was significantly lower among patients who received LAA occlusion compared to NOAC therapy [1.51% vs. 5.60%, RR 0.27 (95% CI 0.14-0.54)], but there were no statistical differences in the composite thrombotic or thromboembolic events [8.17% vs. 7.72%, RR 1.06 (95% CI 0.73-1.53)], ischaemic stroke or TIA [4.69% vs. 5.45%, RR 0.86 (95% CI 0.54-1.38)], venous thromboembolism [1.66% vs. 1.51%, RR 1.10 (95% CI 0.47-2.57)] and intracranial haemorrhage [1.51% vs. 1.51%, RR 1.00 (95% CI 0.42-2.39)]. CONCLUSION: Overall, LAA occlusion might be a suitable alternative to NOAC therapy for stroke prevention in patients with AF.

Exercise-based cardiac rehabilitation vs. percutaneous coronary intervention for chronic coronary syndrome: impact on morbidity and mortality.

AIMS: Accumulating evidence questions the clinical value of percutaneous coronary intervention (PCI) for patients with chronic coronary syndrome (CCS). We therefore compare the impact of exercise-based cardiac rehabilitation (CR) vs. PCI in patients with CCS on 18-month mortality and morbidity, and evaluate the effects of combining PCI with exercise-based CR. METHODS AND RESULTS: A retrospective cohort study was conducted in March 2021. An online, real-world dataset of CCS patients was acquired, utilizing TriNetX, a global federated health research network. Patients with CCS who received PCI were first compared with patients who were prescribed exercise-based CR. Second, we compared patients who received both CR + PCI vs. CR alone. For both comparisons, patients were propensity-score matched by age, sex, race, comorbidities, medications, and procedures. We ascertained 18-month incidence of all-cause mortality, rehospitalization, and cardiovascular comorbidity [stroke, acute myocardial infarction (AMI), and new-onset heart failure]. The initial cohort consisted of 18 383 CCS patients. Following propensity score matching, exercise-based CR was associated with significantly lower odds of all-cause mortality [0.37 (95% confidence interval (CI): 0.29-0.47)], rehospitalization [0.29 (95% CI: 0.27-0.32)], and cardiovascular morbidities, compared to PCI. Subsequently, patients that received both CR + PCI did not have significantly different odds for all-cause mortality [1.00 (95% CI: 0.63-1.60)], rehospitalization [1.00 (95% CI: 0.82-1.23)], AMI [1.11 (95% CI: 0.68-1.81)], and stroke [0.71 (95% CI: 0.39-1.31)], compared to CR only. CONCLUSIONS: Compared to PCI, exercise-based CR associated with significantly lower odds of 18-month all-cause mortality, rehospitalization, and cardiovascular morbidity in patients with CCS, whilst combining PCI and exercise-based CR associated with lower incident heart failure only.

Atrial fibrillation and the risk of 30-day incident thromboembolic events, and mortality in adults ≥ 50 years with COVID-19.

BACKGROUND: There are limited data on the outcomes of adults with coronavirus disease 2019 (COVID-19) and atrial fibrillation (AF). The objectives were to (i) examine associations between AF, 30-day thromboembolic events and mortality in adults with COVID-19 and (ii) examine associations between COVID-19, 30-day thromboembolic events and mortality in adults with AF. METHODS: A study was conducted using a global federated health research network. Adults aged ≥50 years who presented to 41 participating healthcare organizations between 20 January 2020 and 1 September 2020 with COVID-19 were included. RESULTS: For the first objective, 6589 adults with COVID-19 and AF were propensity score matched for age, gender, race, and comorbidities to 6589 adults with COVID-19 without AF. The survival probability was significantly lower in adults with COVID-19 and AF compared to matched adults without AF (82.7% compared to 88.3%, Log-Rank test P < .0001; Risk Ratio (95% confidence interval) 1.61 (1.46, 1.78)) and risk of thromboembolic events was higher in patients with AF (9.9% vs 7.0%, Log-Rank test P < .0001; Risk Ratio (95% confidence interval) 1.41 (1.26, 1.59)). For the second objective, 2454 adults with AF and COVID-19 were propensity score matched to 2454 adults with AF without COVID-19. The survival probability was significantly lower for adults with AF and COVID-19 compared to adults with AF without COVID-19, but there was no significant difference in risk of thromboembolic events. CONCLUSIONS: AF could be an important risk factor for short-term mortality with COVID-19, and COVID-19 may increase risk of short-term mortality amongst adults with AF.

Direct-acting oral anticoagulants use prior to COVID-19 diagnosis and associations with 30-day clinical outcomes.

BACKGROUND: It is unclear if direct-acting oral anticoagulants (DOACs) use before hospitalization due to COVID-19 diagnosis would potentially impact the severity and clinical outcomes thereafter. We compared 30-day hospitalization/re-hospitalization and clinical outcomes between patients on chronic DOAC therapy and patients not on oral anticoagulation (OAC) therapy at time of COVID-19 diagnosis. METHODS: We used data from TriNetX, a global federated health research network. Patients aged ≥18 years who were treated with DOACs at time of COVID-19 diagnosis between 20 January 2020 and 28 February 2021 were included, and matched with patients not on OAC therapy from the same period. All patients were followed-up at 30-days after COVID-19 diagnosis. The primary outcomes were all-cause mortality, hospitalization/re-hospitalization, venous thromboembolism (VTE) and intracranial hemorrhage (ICH). RESULTS: 738,423 patients were included. After propensity score matching (PSM), 26,006 patients remained in the study (13,003 on DOACs; 13,003 not on OAC). DOAC-treated patients (mean age 67.1 ± 15.4 years, 52.2% male) had higher relative risks (RRs) and lower 30-days event-free survival as compared to patients not on OAC for all-cause mortality (RR 1.27, 95% CI 1.12-1.44; Log-Rank test p = 0.010), hospitalization/re-hospitalization (RR 1.72, 95% CI 1.64-1.82; Log-Rank test p < 0.001) and VTE (RR 4.51, 95% CI 3.91-5.82; Log-Rank test p < 0.001), but not for ICH (RR 0.90, 95% CI 0.54-1.51; Log-Rank test p = 0.513). CONCLUSION: In COVID-19 patients, previous DOAC therapy at time of diagnosis was not associated with improved clinical outcomes or lower hospitalization/re-hospitalization rate compared to patients not taking OAC therapy.

Atrial Fibrillation in Patients With Cardiomyopathy: Prevalence and Clinical Outcomes From Real-World Data.

Background Cardiomyopathy is a common cause of atrial fibrillation (AF) and may also present as a complication of AF. However, there is a scarcity of evidence of clinical outcomes for people with cardiomyopathy and concomittant AF. The aim of the present study was therefore to characterize the prevalence of AF in major subtypes of cardiomyopathy and investigate the impact on important clinical outcomes. Methods and Results A retrospective cohort study was conducted using electronic medical records from a global federated health research network, with data primarily from the United States. The TriNetX network was searched on January 17, 2021, including records from 2002 to 2020, which included at least 1 year of follow-up data. Patients were included based on a diagnosis of hypertrophic, dilated, or restrictive cardiomyopathy and concomitant AF. Patients with cardiomyopathy and AF were propensity-score matched for age, sex, race, and comorbidities with patients who had a cardiomyopathy only. The outcomes were 1-year mortality, hospitalization, incident heart failure, and incident stroke. Of 634 885 patients with cardiomyopathy, there were 14 675 (2.3%) patients with hypertrophic, 90 117 (7.0%) with restrictive, and 37 685 (5.9%) with dilated cardiomyopathy with concomitant AF. AF was associated with significantly higher odds of all-cause mortality (odds ratio [95% CI]) for patients with hypertrophic (1.26 [1.13-1.40]) and dilated (1.36 [1.27-1.46]), but not restrictive (0.98 [0.94-1.02]), cardiomyopathy. Odds of hospitalization, incident heart failure, and incident stroke were significantly higher in all cardiomyopathy subtypes with concomitant AF. Among patients with AF, catheter ablation was associated with significantly lower odds of all-cause mortality at 12 months across all cardiomyopathy subtypes. Conclusions Findings of the present study suggest AF may be highly prevalent in patients with cardiomyopathy and associated with worsened prognosis. Subsequent research is needed to determine the usefulness of screening and multisdisciplinary treatment of AF in this population.

Exercise-Based Cardiac Rehabilitation and All-Cause Mortality Among Patients With Atrial Fibrillation.

Background There is limited evidence of long-term impact of exercise-based cardiac rehabilitation (CR) on clinical end points for patients with atrial fibrillation (AF). We therefore compared 18-month all-cause mortality, hospitalization, stroke, and heart failure in patients with AF and an electronic medical record of exercise-based CR to matched controls. Methods and Results This retrospective cohort study included patient data obtained on February 3, 2021 from a global federated health research network. Patients with AF undergoing exercise-based CR were propensity-score matched to patients with AF without exercise-based CR by age, sex, race, comorbidities, cardiovascular procedures, and cardiovascular medication. We ascertained 18-month incidence of all-cause mortality, hospitalization, stroke, and heart failure. Of 1 366 422 patients with AF, 11 947 patients had an electronic medical record of exercise-based CR within 6-months of incident AF who were propensity-score matched with 11 947 patients with AF without CR. Exercise-based CR was associated with 68% lower odds of all-cause mortality (odds ratio, 0.32; 95% CI, 0.29-0.35), 44% lower odds of rehospitalization (0.56; 95% CI, 0.53-0.59), and 16% lower odds of incident stroke (0.84; 95% CI, 0.72-0.99) compared with propensity-score matched controls. No significant associations were shown for incident heart failure (0.93; 95% CI, 0.84-1.04). The beneficial association of exercise-based CR on all-cause mortality was independent of sex, older age, comorbidities, and AF subtype. Conclusions Exercise-based CR among patients with incident AF was associated with lower odds of all-cause mortality, rehospitalization, and incident stroke at 18-month follow-up, supporting the provision of exercise-based CR for patients with AF.