Predicting Adverse Events beyond Stroke and Bleeding with the ABC-Stroke and ABC-Bleeding Scores in Patients with Atrial Fibrillation: The Murcia AF Project

Background The ABC (age, biomarkers, and clinical history)-stroke and ABC-bleeding are biomarker-based scores proposed to predict stroke and bleeding, but non-specificity of biomarkers is common, predicting different clinical events at the same time. We assessed the predictive performance of the ABC-stroke and ABC-bleeding scores, for outcomes beyond ischemic stroke and major bleeding, in a cohort of atrial fibrillation (AF) patients. Methods We included AF patients stable on vitamin K antagonists for 6 months. The ABC-stroke and ABC-bleeding were calculated and the predictive values for myocardial infarction (MI), acute heart failure (HF), a composite of cardiovascular events, and all-cause deaths were compared. Results We included 1,044 patients (49.2% male; median age 76 [71–81] years). During 6.5 (4.3–7.9) years, there were 58 (5.6%) MIs, 98 (9.4%) acute HFs, 167 (16%) cardiovascular events, and 418 (40%) all-cause deaths. There were no differences in mean ABC-stroke and ABC-bleeding scores in patients with/without MI (p = 0.367 and p = 0.286, respectively); both scores were higher in patients with acute HF, cardiovascular events, or death (all p  0.70). Clinical usefulness whether assessed by ABC-stroke or ABC-bleeding was similar for various primary endpoints. Conclusion In AF patients, the ABC-stroke and ABC-bleeding scores demonstrated similar predictive ability for outcomes beyond stroke and bleeding, including MI, acute HF, a composite of cardiovascular events, and all-cause deaths. This is consistent with nonspecificity of biomarkers that predict “sick” patients or poor prognosis overall

Prediction of Residual Stroke Risk in Anticoagulated Patients with Atrial Fibrillation: mCARS

Our ability to evaluate residual stroke risk despite anticoagulation in atrial fibrillation (AF) is currently lacking. The Calculator of Absolute Stroke Risk (CARS) has been proposed to predict 1-year absolute stroke risk in non-anticoagulated patients. We aimed to determine whether a modified CARS (mCARS) may be used to assess the residual stroke risk in anticoagulated AF patients from ‘real-world’ and ‘clinical trial’ cohorts. We studied patient-level data of anticoagulated AF patients from the real-world Murcia AF Project and AMADEUS clinical trial. Individual mCARS were estimated for each patient. None of the patients were treated with non-vitamin K antagonist oral anticoagulants. The predicted residual stroke risk was compared to actual stroke risk. 3503 patients were included (2205 [62.9%] clinical trial and 1298 [37.1%] real-world). There was wide variation of CARS for each category of CHA(2)DS(2)-VASc score in both cohorts. Average predicted residual stroke risk by mCARS (1.8 ± 1.8%) was identical to actual stroke risk (1.8% [95% CI, 1.3–2.4]) in the clinical trial, and broadly similar in the real-world (2.1 ± 1.9% vs. 2.4% [95% CI, 1.6–3.4]). AUCs of mCARS for prediction of stroke events in the clinical trial and real-world were 0.678 (95% CI, 0.598–0.758) and 0.712 [95% CI, 0.618–0.805], respectively. mCARS was able to refine stroke risk estimation for each point of the CHA(2)DS(2)-VASc score in both cohorts. Personalised residual 1-year absolute stroke risk in anticoagulated AF patients may be estimated using mCARS, thereby allowing an assessment of the absolute risk reduction of treatment and facilitating a patient-centred approach in the management of AF. Such identification of patients with high residual stroke risk could help target more aggressive interventions and follow-up

Predicting Bleeding Events in Anticoagulated Patients With Atrial Fibrillation: A Comparison Between the HAS-BLED and GARFIELD-AF Bleeding Scores

Background Patients with atrial fibrillation (AF) treated with oral anticoagulants may be exposed to an increased risk of bleeding events. The HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile INRs, Elderly, Drugs or alcohol) score is a simple, well-established, clinical bleeding-risk prediction score. Recently, a new algorithm-based score was proposed, the GARFIELD-AF (Global Anticoagulant in the Field-AF) bleeding score. We compared HAS-BLED and GARFIELD-AF scores in predicting adjudicated bleeding events in a clinical trial cohort of patients with AF taking anticoagulants, in the first external comparative validation of both scores. Methods and Results We analyzed patients from the SPORTIF (Stroke Prevention Using an Oral Thrombin Inhibitor in Patients With AF) III and V trials. All patients assigned to the warfarin arm with information to calculate the scores were considered. Outcomes were major, major/clinically relevant nonmajor, and any bleeding. A total of 3550 warfarin-treated patients were available for analysis. Of these patients, 2519 (71.0%) had a HAS-BLED score ≥3, whereas based on GARFIELD-AF median value, 2056 (57.9%) were categorized as "high score." Both HAS-BLED and GARFIELD-AF C-indexes showed modest predictive value (C-index [95% confidence interval] for major bleeding, 0.58 [0.56-0.60] and 0.56 [0.54-0.57], respectively); however, GARFIELD-AF was not predictive of any bleeding. The GARFIELD-AF bleeding score had a significantly lower sensitivity and a negative reclassification for any bleeding compared with HAS-BLED, assessed by integrated discrimination improvement and net reclassification improvement (both P<0.001). HAS-BLED showed a 5% net benefit for any bleeding occurrence. Conclusions The algorithm-based GARFIELD-AF bleeding score did not show any significant improvement in major and major/clinically relevant nonmajor prediction compared with the simple HAS-BLED score. For clinical usefulness in prediction of any bleeding, the HAS-BLED score showed a significant net benefit compared with the GARFIELD-AF

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

Abstract 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

Chronic Oral Anticoagulation Therapy and Prognosis of Patients Admitted to Hospital for COVID-19: Insights from the HOPE COVID-19 Registry

BackgroundMost evidence regarding anticoagulation and COVID-19 refers to the hospitalization setting, but the role of oral anticoagulation (OAC) before hospital admission has not been well explored. We compared clinical outcomes and short-term prognosis between patients with and without prior OAC therapy who were hospitalized for COVID-19.MethodsAnalysis of the whole cohort of the HOPE COVID-19 Registry which included patients discharged (deceased or alive) after hospital admission for COVID-19 in 9 countries. All-cause mortality was the primary endpoint. Study outcomes were compared after adjusting variables using propensity score matching (PSM) analyses.Results7698 patients were suitable for the present analysis (675 (8.8%) on OAC at admission: 427 (5.6%) on VKAs and 248 (3.2%) on DOACs). After PSM, 1276 patients were analyzed (638 with OAC; 638 without OAC), without significant differences regarding the risk of thromboembolic events (OR 1.11, 95% CI 0.59-2.08). The risk of clinically relevant bleeding (OR 3.04, 95% CI 1.92-4.83), as well as the risk of mortality (HR 1.22, 95% CI 1.01-1.47; log-rank p value = 0.041), was significantly increased in previous OAC users. Amongst patients on prior OAC only, there were no differences in the risk of clinically relevant bleeding, thromboembolic events, or mortality when comparing previous VKA or DOAC users, after PSM.ConclusionHospitalized COVID-19 patients on prior OAC therapy had a higher risk of mortality and worse clinical outcomes compared to patients without prior OAC therapy, even after adjusting for comorbidities using a PSM. There were no differences in clinical outcomes in patients previously taking VKAs or DOACs. This trial is registered with NCT04334291/EUPAS34399

Cardiovascular risk factors, cardiovascular disease, and COVID-19: an umbrella review of systematic reviews

AIMS: To consolidate evidence to determine (i) the association between cardiovascular risk factors and health outcomes with coronavirus 2019 (COVID-19); and (ii) the impact of COVID-19 on cardiovascular health. METHODS AND RESULTS: An umbrella review of systematic reviews was conducted. Fourteen medical databases and pre-print servers were searched from 1 January 2020 to 5 November 2020. The review focused on reviews rated as moderate or high-quality using the AMSTAR 2 tool. Eighty-four reviews were identified; 31 reviews were assessed as moderate quality and one was high-quality. The following risk factors were associated with higher mortality and severe COVID-19: renal disease [odds ratio (OR) (95% confidence interval) for mortality 3.07 (2.43–3.88)], diabetes mellitus [OR 2.09 (1.80–2.42)], hypertension [OR 2.50 (2.02–3.11)], smoking history [risk ratio (RR) 1.26 (1.20–1.32)], cerebrovascular disease [RR 2.75 (1.54–4.89)], and cardiovascular disease [OR 2.65 (1.86–3.78)]. Liver disease was associated with higher odds of mortality [OR 2.81 (1.31–6.01)], but not severe COVID-19. Current smoking was associated with a higher risk of severe COVID-19 [RR 1.80 (1.14–2.85)], but not mortality. Obesity associated with higher odds of mortality [OR 2.18 (1.10–4.34)], but there was an absence of evidence for severe COVID-19. In patients hospitalized with COVID-19, the following incident cardiovascular complications were identified: acute heart failure (2%), myocardial infarction (4%), deep vein thrombosis (7%), myocardial injury (10%), angina (10%), arrhythmias (18%), pulmonary embolism (19%), and venous thromboembolism (25%). CONCLUSION: Many of the risk factors identified as associated with adverse outcomes with COVID-19 are potentially modifiable. Primary and secondary prevention strategies that target cardiovascular risk factors may improve outcomes for people following COVID-19

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

BackgroundSodium-glucose co-transporter 2 inhibitors (SGLT2i) have been associated with favourable outcomes in patients with prevalent HF.PurposeWe investigated the impact of SGLT2i on the risk of incident HF and adverse cardiovascular outcomes.MethodsAll diabetic patients between January 2018 and December 2019 were identified from a federated electronic medical record database (TriNetX) and followed up for 2 years. 1:1 propensity-score matching (PSM) analysis was performed to balance the SGLT2i and non-SGLT2i cohorts. The primary outcome was incident HF. Secondary outcomes included all-cause mortality, cardiac arrest, VT/VF, incident AF, ischaemic stroke/TIA, composite of arterial and venous thrombotic events, and composite of incident VT/VF and cardiac arrest.Results115,749 and 2,316,638 patients were treated with and without SGLT2is respectively. After PSM, 115,749 patients remained in each group. The risk of incident HF was significantly lower in the SGLT2i cohort compared to the non-SGLT2i cohort (HR 0.70, 95%CI 0.68-0.73). SGLT2i 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).ConclusionSGLT2i use was associated with a significant reduction in the risk of incident HF and adverse cardiovascular outcomes but not ventricular arrhythmias. This article is protected by copyright. All rights reserved

Relationship between temporal rhythm-based classification of atrial fibrillation and stroke: real-world vs. clinical trial

BACKGROUND: The risk of stroke according to clinical classification of atrial fibrillation (AF) remains poorly defined. Here, we assessed the impact of AF type on stroke risk in vitamin K antagonist-treated patients with AF in ‘real-world’ and ‘clinical trial’ cohorts. METHODS: Post-hoc analysis of patient-level data from the Murcia AF Project and AMADEUS trial. Clinical classification of AF was based on contemporary recommendations from international guidelines. Study endpoint was the incidence rate of ischaemic stroke. Stroke risk was determined using CHA(2)DS(2)-VASc score and CARS. A modified CHA(2)DS(2)-VAS‘c’ score that applied one additional point for a ‘c’ criterion of continuous AF (i.e. non-paroxysmal AF) was calculated. RESULTS: We included 5,917 patients: 1,361 (23.0%) real-world and 4,556 (77.0%) clinical trial. Baseline demographics were balanced in the real-world cohort but clinical trial participants with non-pAF (vs. pAF) were older, male-predominant and had more comorbidities. Crude stroke rates were comparable between the groups in real-world patients (IRR 0.72 [95% CI,0.37-1.28], p = 0.259) though clinical trial participants with non-pAF had a significantly higher crude rate of stroke events (IRR 4.66 [95%,CI,2.41-9.48], p  0.05). CONCLUSIONS: Overall, our results support the need for anticoagulation based on thromboembolic risk profile rather than AF type. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11239-022-02638-0

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. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00392-021-01983-z