Incident heart failure, arrhythmias and cardiovascular outcomes with sodium-glucose cotransporter 2 (SGLT2) inhibitor use in patients with diabetes: Insights from a global federated electronic medical record database.

AIM: To investigate the impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on the risk of incident heart failure and adverse cardiovascular outcomes. METHODS: All patients with diabetes who were registered between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. A 1:1 propensity-score matching (PSM) analysis was performed to balance the SGLT2 inhibitor and non-SGLT2 inhibitor cohorts. The primary outcome was incident heart failure. Secondary outcomes included all-cause mortality, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF), incident atrial fibrillation (AF), ischaemic stroke/transient ischaemic attack (TIA), composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest. RESULTS: A total of 131 189 and 2 692 985 patients were treated with and without SGLT2 inhibitors, respectively. After PSM, 131 188 patients remained in each group. The risk of incident heart failure was significantly lower in the SGLT2 inhibitor cohort compared to the non-SGLT2 inhibitor cohort (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.68-0.73). SGLT2 inhibitor use was also associated with a significantly lower risk of all-cause mortality (HR 0.61, 95% CI 0.58-0.64), cardiac arrest (HR 0.70, 95% CI 0.63-0.78), incident AF (HR 0.81, 95% CI 0.76-0.84), ischaemic stroke/TIA (HR 0.90, 95% CI 0.88-0.93), composite of arterial and venous thrombotic events (HR 0.90, 95% CI 0.88-0.92), and composite of incident VT/VF and cardiac arrest (HR 0.76, 95% CI 0.71-0.81). There were no significant differences for VT/VF (HR 0.94, 95% CI 0.88-1.00). CONCLUSION: Use of SGLT2 inhibitors was associated with a significant reduction in the risk of incident heart failure and adverse cardiovascular outcomes but not ventricular arrhythmias.

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.

Outcomes in patients with ischaemic stroke undergoing endovascular thrombectomy: Impact of atrial fibrillation.

OBJECTIVES: Endovascular thrombectomy (EVT) is associated with good clinical outcomes in ischaemic stroke, but the risk of intracerebral haemorrhage (ICH) and mortality remains common following ischaemic stroke. The effect of concomitant atrial fibrillation (AF) on clinical outcomes following acute ischaemic stroke in patients receiving EVT remains unclear. The aim is to investigate associations between AF and intracerebral haemorrhage and all-cause mortality at 90 days in patients with ischaemic stroke undergoing EVT. MATERIALS AND METHODS: A retrospective cohort was conducted using TriNetX, a global health research network. The network was searched for people aged ≥18 years with ischaemic stroke, EVT and AF recorded in electronic medical records between 01/09/2018 and 01/09/2021. These patients were compared to controls with ischaemic stroke, EVT and no AF. Propensity score matching for age, sex, race, comorbidities, National Institutes of Health Stroke Scale (NIHSS) scores, and prior use of anticoagulation was used to balance the cohorts with and without AF. RESULTS: In total 3,106 patients were identified with history of ischaemic stroke treated by EVT. After propensity-score matching, 832 patients (mean age 68 ± 13; 47% female) with ischaemic stroke, EVT and AF, were compared to 832 patients (mean age 67 ± 12; 47% female) with ischaemic stroke, EVT and no history of AF. In the cohort with AF, 11.5% (n = 96) experienced ICH within 90 days following EVT, compared with 12.3% (n = 103) in patients without AF (Odds Ratio (OR) 0.92, 95% confidence interval (CI) 0.68-1.24; p = 0.59). In the patients with AF, mortality within 90 days following EVT was 18.7% (n = 156), compared with 22.5% in patients without AF (n = 187) (OR 0.79, 95% CI 0.63-1.01; p = 0.06). CONCLUSION: In patients with ischaemic stroke undergoing EVT, AF was not significantly associated with intracerebral haemorrhage or all-cause mortality at 90-day follow-up.

Stroke-Heart Syndrome: Incidence and Clinical Outcomes of Cardiac Complications Following 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 following a stroke. Following a stroke, individuals have an increased risk of new-onset cardiovascular complications. However, the incidence and long-term clinical consequence of newly diagnosed cardiovascular complications following a stroke is unclear. The aim of the present study was to investigate the incidence and long-term clinical outcomes of newly diagnosed cardiovascular complications following incident ischemic stroke. METHODS: A retrospective cohort study was conducted using anonymized electronic medical records from 53 participating health care organizations. Patients with incident ischemic stroke aged ≥18 years with 5 years of follow-up were included. Patients who were diagnosed with new-onset cardiovascular complications (heart failure, severe ventricular arrhythmia, atrial fibrillation, ischemic heart disease, Takotsubo syndrome) within 4-weeks (exposure) of incident ischemic stroke were 1:1 propensity score-matched (age, sex, ethnicity, comorbidities, cardiovascular care) with ischemic stroke patients who were not diagnosed with a new-onset cardiovascular complication (control). Logistic regression models produced odds ratios (OR) with 95% CIs for 5-year incidence of all-cause mortality, recurrent stroke, hospitalization, and acute myocardial infarction. RESULTS: Of 365 383 patients with stroke with 5-year follow-up: 11.1% developed acute coronary syndrome; 8.8% atrial fibrillation/flutter; 6.4% heart failure; 1.2% severe ventricular arrythmias; and 0.1% Takotsubo syndrome within 4 weeks of incident ischemic stroke. Following propensity score matching, odds of 5-year all-cause mortality were significantly higher in stroke patients with acute coronary syndrome (odds ratio, 1.49 [95% CI, 1.44-1.54]), atrial fibrillation/flutter (1.45 [1.40-1.50]), heart failure (1.83 [1.76-1.91]), and severe ventricular arrhythmias (2.08 [1.90-2.29]), compared with matched controls. Odds of 5-year rehospitalization and acute myocardial infarction were also significantly higher for patients with stroke diagnosed with new-onset cardiovascular complications. Takotsubo syndrome was associated with significantly higher odds of 5-year composite major adverse cardiovascular events (1.89 [1.29-2.77]). Atrial fibrillation/flutter was the only new-onset cardiac complication associated with significantly higher odds of recurrent ischemic stroke at 5 years (1.10 [1.07-1.14]). CONCLUSIONS: New-onset cardiovascular complications diagnosed following an ischemic stroke are very common and associate with significantly worse 5-year prognosis in terms of major adverse cardiovascular events. People with stroke and newly diagnosed cardiovascular complications had >50% prevalence of recurrent stroke at 5 years.

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.

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.

Associations between COVID-19 and 30-day thromboembolic events and mortality in people with dementia receiving antipsychotic medications.

BACKGROUND: Antipsychotic medications are frequently prescribed to people with dementia to manage behavioural and psychological symptoms. Using a global federated research network, the objectives were to determine: 1) if COVID-19 is associated with 30-day thromboembolic events and mortality for people with dementia receiving antipsychotic medications; and 2) if the proportion of people with dementia receiving antipsychotics is higher during the COVID-19 pandemic compared to 2019. METHODS: A retrospective cohort study was conducted using TriNetX, a global federated health research network. The network was searched for people aged ≥ 65 years with dementia, COVID-19 and use of antipsychotics in the 30-days prior to COVID-19 recorded in electronic medical records between 20/01/2020 and 05/12/2020. These individuals were compared to historical controls from 2019 with dementia and use of antipsychotics in the 30-days before a visit to a participating healthcare organisation. Propensity score matching for age, sex, race, co-morbidities and use of antidepressants and anticonvulsants was used to balance cohorts with and without COVID-19. RESULTS: Within the TriNetX network, 8414 individuals with COVID-19, dementia and use of antipsychotics and 31,963 historical controls were identified. After propensity score matching there were 8396 individuals with COVID-19 and 8396 historical controls. The cohorts were well balanced for age, sex, race, co-morbidities and use of antidepressants and anticonvulsants. The odds of 30-day thromboembolic events and all-cause mortality were significantly higher in adults with COVID-19 (Odds Ratios: 1.36 (95% confidence interval (CI): 1.21-1.52) and 1.93 (1.71-2.17), respectively). The number of people with dementia with a visit to a participating healthcare organisation was lower between 20/01/2020 and 05/12/2020 (n = 165,447) compared to the same period in 2019 (n = 217,391), but the proportion receiving antipsychotics increased from 14.7% (95%CI: 14.6-14.9%) to 16.4% (95%CI: 16.2-16.5%), P < .0001. CONCLUSIONS: These findings add to the evidence base that during the COVID-19 pandemic there was an increase in the proportion of people with dementia receiving antipsychotics. The negative effects of antipsychotics in patients with dementia may be compounded by concomitant COVID-19.

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).

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.

Direct oral anticoagulants are associated with lower risk of dementia in patients with atrial fibrillation.

BACKGROUND AND AIM: Atrial fibrillation (AF) is associated with increased risk of dementia. Whether direct oral anticoagulation (DOAC) reduce this risk compared to vitamin-K antagonist (VKA) is unclear. The aim of this study was to assess the risk of new all-cause dementia and vascular dementia in AF patients, treated with either DOAC or VKAs. METHODS: Anonymized electronic medical records from the TriNetX federated research network were used. AF patients treated with DOACs within 1 month of AF diagnosis, were 1:1 propensity score-matched with those treated with a VKA. The analysis included patients who completed 5 and 10 years of follow-up and were assessed for all-cause dementia and vascular dementia. Cox proportional hazard models were used to hazard ratios (HR), respectively with 95% confidence intervals (CIs). RESULTS: Among patients who completed 5 years of follow-up, after propensity score matching the final cohort consisted of 215,404 well-matched AF patients. All-cause dementia was diagnosed in 4,153 (3.9%) patients among those treated with DOACs and 4,150 (3.9%) among the VKA-treated patients (HR: 1.01, 95%CI: 0.96-1.05). Among patients 65-74 years old who were followed, DOAC treatment was associated with lower risk of dementia compared to VKAs (HR: 0.72; 95%CI: 0.59-0.86). Among patients who completed 10 years of follow-up, after propensity score matching the final cohort consisted of 19,208 well-matched AF patients. All-cause dementia was diagnosed in 314 (3.3%) patients among those treated with DOACs and 451 (4.7%) among the VKA-treated patients. DOAC treatment was associated with significantly lower risk of all-cause dementia during a follow-up period of 10 years compared to VKA treatment (HR: 0.72, 95%CI: 0.62-0.83), which remained consistent in patiens ≥65 years old. CONCLUSION: This propensity-score matched analysis showed that among AF patients, treatment with a DOACs for a period of 10 years was associated with lower risk of all-cause dementia and vascular dementia compared to VKA treatment, an effect which was not apparent in those treated for shorter duration. This finding requires confirmation in ongoing randomised controlled trials.

C-reactive protein levels are associated with early cardiac complications or death in patients with acute ischemic stroke: a propensity-matched analysis of a global federated health from the TriNetX network.

The role of inflammation in predicting early cardiac complications among stroke patients is unclear. Electronic medical records from TriNetX, a global federated health research network, were used for this retrospective analysis. Patients with ischemic stroke and C-Reactive Protein (CRP) levels measured within 24 h post-stroke were categorized into three groups: (i) < 1 mg/L, (ii)1-3 mg/L and (iii) > 3 mg/L. The primary outcome was a composite outcome of cardiac complications (heart failure (HF), ischemic heart disease, atrial fibrillation (AF), ventricular arrhythmias and Takotsubo cardiomyopathy) or death at 30 days from the index event. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Of the 104,741 patients enrolled, 51% were female and the mean age was 66 ± 16 years. After PSM, a new cardiac complication or death within 30 days occurred in 5624 (33.1%) patients with CRP > 3 mg/L, in 4243 (25.6%) patients with CRP 1-3 mg/L and in 3891 (23.5%) patients with CRP < 1 mg/L. Patients with CRP levels of 1-3 mg/L and > 3 mg/L had higher risk of the composite outcome (HR 1.10, 95%CI 1.05-1.52; HR 1.51, 95%CI 1.45-1.58), death (HR 1.43, 95%CI 1.24-1.64; HR 3.50, 95%CI 3.01-3.96), HF (HR 1.08, 95%CI 1.01-1.16; HR 1.51, 95%CI 1.41-1.61), AF (HR 1.10, 95% CI:1.02-1.18; HR 1.42, 95%CI 1.33-1.52) and ventricular arrhythmias (HR 1.25, 95%CI 1.02-1.52; HR 1.67, 95% CI 1.38-2.01) compared to those with CRP < 1 mg/L. Ischemic heart disease were more common among patients with CRP levels > 3 mg/L compared to those with CRP < 1 mg/L (HR:1.33, 95% CI:1.26-1.40), while no association with Takotsubo cardiomyopathy was found in all the analyses. CRP levels within the first 24 h of an ischemic stroke predict 30-day cardiac complications or death.

Thoracic aortic aneurysm and atrial fibrillation: clinical associations with the risk of stroke from a global federated health network analysis.

BACKGROUND: An association with aortic aneurysm has been reported among patients with atrial fibrillation (AF). The aims of this study were to investigate the prevalence of thoracic aorta aneurysm (TAA) among patients with AF and to assess whether the co-presence of TAA is associated with a higher risk of adverse clinical outcomes. METHODS AND RESULTS: Using TriNetX, a global federated health research network of anonymised electronic medical records, all adult patients with AF, were categorised into two groups based on the presence of AF and TAA or AF alone. Between 1 January 2017 and 1 January 2019, 874,212 people aged ≥ 18 years with AF were identified. Of these 17,806 (2.04%) had a TAA. After propensity score matching (PSM), 17,805 patients were included in each of the two cohorts. During the 3 years of follow-up, 3079 (17.3%) AF patients with TAA and 2772 (15.6%) patients with AF alone, developed an ischemic stroke or transient ischemic attack (TIA). The risk of ischemic stroke/TIA was significantly higher in patients with AF and TAA (HR 1.09, 95% CI 1.04-1.15; log-rank p value < 0.001) The risk of major bleeding was higher in patients with AF and TAA (OR 1.07, 95% CI 1.01-1.14), but not significant in time-dependent analysis (HR 1.04, 95% CI 0.98-1.10; log-rank p value = 0.187), CONCLUSION: This retrospective analysis reports a clinical concomitance of the two medical conditions, and shows in a PSM analysis an increased risk of ischemic events in patients affected by TAA and AF compared to AF alone.

Cerebrovascular, Cognitive and Cardiac Benefits of SGLT2 Inhibitors Therapy in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus: Results from a Global Federated Health Network Analysis.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are effective anti-diabetic drugs improving cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients. This study investigated cardiovascular, cerebrovascular and cognitive outcomes of SGLT2i therapy in patients with atrial fibrillation (AF) and T2DM. METHODS: Observational study using TriNetX, a global health research network of anonymised electronic medical records from real-world patients between January 2018 and December 2019. The network includes healthcare organisations globally but predominately in the United States. AF patients (ICD-10-CM code: I48) with T2DM were divided according to SGLT2i use or not, and balanced using propensity score matching (PSM). Patients were followed-up for 3-years. The primary endpoints were ischaemic stroke/transient ischemic attack (TIA), intracranial haemorrhage (ICH), and incident dementia. Secondary endpoints were incident heart failure and mortality. RESULTS: We identified 89,356 AF patients with T2DM of which 5061 (5.7%) were taking a SGLT2i. After PSM, 5049 patients (mean age 66.7 ± 10.6 years; 28.9% female) were included in each group. At 3-years follow-up, the risk of ischaemic stroke/TIA was higher in patients not receiving SGLT2i (HR 1.12, 95% CI 1.01-1.24) and for ICH (HR 1.57, 95% CI 1.25-1.99) and incident dementia (HR 1.66, 95% CI 1.30-2.12). Incident heart failure (HR 1.50, 95% CI 1.34-1.68) and mortality (HR 1.77, 95% CI 1.58-1.99) risks were increased in AF patients not receiving SGLT2i. CONCLUSIONS: In our large 'real world' analysis of patients with concomitant AF and T2DM, SGLT2i reduced the risk of cerebrovascular events, incident dementia, heart failure and death.

Clinical implications of different types of dementia in patients with atrial fibrillation: Insights from a global federated health network analysis.

BACKGROUND: Atrial fibrillation (AF) associates with higher Alzheimer's disease (AD) and vascular dementia risks but the clinical implications have been scarcely investigated. We examined the association between AD or vascular dementia and adverse outcomes in AF patients. METHODS: Cohort study between January 2000 and 2017. AF patients were divided into two groups according to vascular dementia or AD, and balanced using propensity score matching (PSM). During 4-years of follow-up, incident intracranial hemorrhages (ICH), the composite of ischemic stroke/transient ischemic attack (TIA), hospitalizations, and all-cause deaths, were recorded. RESULTS: Two thousand three hundred seventy-seven AF patients with dementia (1225 with vascular dementia, and 1152 with AD) were identified. Following a PSM, 615 patients were included in each cohort (i.e., 1:1) and all variables were well-matched. After PSM, 22 (3.6%) patients with vascular dementia and 55 (8.1%) patients with AD had incident ICH during follow-up (hazard ratio [HR]: 2.22, 95% confidence interval [CI]: 1.33-3.70, log-rank p = 0.002). Overall, 237 (38.5%) patients with vascular dementia and 193 (31.4%) patients with AD, developed an ischemic stroke/TIA. The risk of ischemic stroke/TIA was 1.32-fold higher in vascular dementia (HR: 1.32, 95% CI: 1.09-1.59, log-rank p = 0.003). The risk of rehospitalization (HR: 1.14, 95% CI: 1.01-1.31), and mortality (HR: 1.25, 95% CI: 1.01-1.58) were also higher among AF patients with vascular dementia compared to AD. CONCLUSIONS: The two forms of dementia in AF patients are associated with different prognosis, with AD being associated with a higher risk of ICH, and vascular dementia with a higher risk of stroke/TIA, hospitalization, and mortality.

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.

Oral anticoagulants and outcomes in adults ≥80 years with atrial fibrillation: A global federated health network analysis.

BACKGROUND: The objective of this study was to determine associations between use of oral anticoagulation (OAC) and stroke and bleeding-related outcomes for older people ≥80 years with atrial fibrillation (AF), and to determine trends over time in prescribing of OAC for this population. METHODS: A retrospective cohort study was conducted. People aged ≥80 years with AF receiving (1) no OAC; (2) warfarin; or (3) a non-vitamin-K antagonist oral anticoagulant (NOAC) between 2011 and 2019 were included. Propensity score matching was used to balance cohorts (no OAC, warfarin or a NOAC) on characteristics including age, sex, ethnicity, and co-morbidities. Cox proportional hazard models were used to derive hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: The proportion of people aged ≥80 years receiving any OAC increased from 32.4% (n = 27,647) in 2011 to 43.6% (n = 110,412) in 2019. After propensity score matching, n = 169,067 individuals were included in the cohorts receiving no OAC or a NOAC. Compared to no OAC, participants receiving a NOAC had a lower risk of incident dementia (hazHR 0.68, 95% CI 0.65-0.71), all-cause mortality (HR 0.49, 95% CI 0.48-0.50), first-time ischaemic stroke (HR 0.87, 95% CI 0.83-0.91), and a higher risk of major bleeding (HR 1.08, 95% CI 1.05-1.11). Compared to participants receiving warfarin, participants receiving a NOAC had a lower risk of dementia (HR 0.90, 95% CI: 0.86-0.93), all-cause mortality (HR 0.74, 95% CI: 0.72-0.76), ischaemic stroke (HR 0.86, 95% CI: 0.82-0.90) and major bleeding (HR 0.88, 95% CI: 0.85-0.90). Similar results were observed when only including people with additional bleeding risk factors. CONCLUSIONS: The proportion of people aged ≥80 years receiving OAC has increased since the introduction of NOACs, but remains low. Use of a NOAC was associated with improved outcomes compared to warfarin, and compared to no OAC, except for a small but statistically significant higher risk of major bleeding.

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.