Adverse Cardiovascular Complications Following Prescription of Programmed Cell Death 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) Inhibitors: A Propensity-Score Matched Cohort Study With Competing Risk Analysis

Abstract Background: Programmed death-1 (PD-1) and programmed death- ligand 1 (PD-L1) inhibitors, such as pembrolizumab, nivolumab and atezolizumab, are major classes of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, their use is associated with adverse cardiovascular events. We examined the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors.Methods: Patients receiving PD-1 or PD-L1 inhibitors since their launch up to 31st December 2019 at the Hospital Authority of Hong Kong, without pre-existing cardiac complications were included. The primary outcome was a composite of incident heart failure, acute myocardial infarction, atrial fibrillation or atrial flutter with the last follow-up date of 31st December 2020. Propensity score matching between PD-L1 inhibitor use and PD-1 inhibitor use with a 1:2 ratio for patient demographics, past comorbidities and non-PD-1/PD-L1 medications was performed.Results: A total of 1959 patients were included. Over a median follow-up of 247 days (interquartile range [IQR]: 72-506), 320 (incidence rate [IR]: 16.31%) patients met the primary outcome after PD-1/PD-L1 treatment: 244 (IR: 12.57%) with heart failure, 38 (IR: 1.93%) with acute myocardial infarction, 54 (IR: 2.75%) with atrial fibrillation, 6 (IR: 0.31%) with atrial flutter. Compared with PD-1 inhibitor treatment, PD-L1 inhibitor treatment was significantly associated with a lower risk of composite outcome both before (hazard ratio [HR]: 0.32, 95% CI: [0.18-0.59], P value=0.0002) and after matching (HR: 0.34, 95% CI: [0.18-0.65], P value=0.001), and lower all-cause mortality risk before matching (HR: 0.77, 95% CI: [0.64-0.93], P value=0.0078) and after matching (HR: 0.80, 95% CI: [0.65-1.00], P value=0.0463). Patients who developed cardiac complications had shorter average readmission intervals and a higher number of hospitalizations after treatment with PD-1/PD-L1 inhibitors both before and after matching (P value<0.0001). Competing risk analysis with cause-specific hazard and subdistribution hazard models, and multiple approaches based on the propensity score all confirmed these observations. Conclusions: Compared with PD-1 treatment, PD-L1 treatment was significantly associated with lower risk of new onset cardiac composite outcome and all-cause mortality both before and after propensity score matching.

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MO129COMPARATIVE EFFECTIVENESS OF SGLT2I VERSUS DPP4I ON CARDIOVASCULAR AND RENAL OUTCOMES IN ROUTINE-CARE SETTINGS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab092.007 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Edouard Fu ◽

Marco Trevisan ◽

Vivekananda Lanka ◽

Catherine M Clase ◽

Yang Xu ◽

...

Keyword(s):

Propensity Score ◽

Kidney Function ◽

Primary Outcome ◽

Cox Regression ◽

Routine Care ◽

Major Adverse Cardiovascular Events ◽

All Cause Mortality ◽

Kidney Function Decline ◽

Egfr Slope

Abstract Background and Aims While clinical trials have demonstrated the efficacy of SGLT2 inhibitors on preventing cardiovascular and renal damage, few studies have expanded this evidence to routine-care settings. Method We compared clinical outcomes of adults who started SGLT2i or DPP4i therapy in Stockholm, Sweden, during 2013-2019. The primary outcome was a composite of cardiovascular (CV) death and hospitalization for heart failure (HF). Secondary outcomes included major adverse cardiovascular events (MACE; composite of cardiovascular death, myocardial infarction, stroke), all-cause mortality and the rate of eGFR decline (eGFR slope). Propensity score weighted Cox regression was used to balance 55 variables and estimate intention-to-treat hazard ratios with 95% confidence intervals. Differences in eGFR slope were calculated with linear mixed models. Results We identified 7136 individuals starting SGLT2i and 13,618 starting DPP4i therapy. Median age was 64 years (37% women) and median eGFR 86 ml/min/1.73m2. During median follow-up of 2.1 years, 211 individuals developed the primary outcome, 269 experienced MACE and 178 died. After propensity score weighting, patients starting SGLT2i therapy were at lower risk for the composite of CV death/HF hospitalization (HR 0.71; 95% CI 0.53-0.94) compared with DPP4i, and showed a tendency towards lower MACE (0.84; 95% CI 0.67-1.04) and all-cause mortality (0.85; 95% CI 0.62-1.18). There were a median of 4 (interquartile range: 2-8) eGFR measurements during follow-up per patient to estimate their eGFR slopes. In adjusted models, new users of SGLT2i had a slower rate of kidney function decline compared with DPP4i (eGFR slope difference of 0.43 (95% CI 0.15-0.72) ml/min/1.73m2 per year). Results for the primary outcome were consistent across 7 pre-specified subgroups, including eGFR (eGFR ≥60: HR 0.79 [95% CI 0.57-1.08]; eGFR <60: HR 0.62 [0.38-0.99], p-value for interaction 0.40). Conclusion In patients undergoing routine care, initiation of SGLT2i was associated with fewer cardiovascular outcomes and less rapid kidney function decline compared with DPP4i initiation.

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Effect of tocilizumab in hospitalized patients with severe pneumonia COVID-19: a cohort study

10.1101/2020.06.06.20122341 ◽

2020 ◽

Cited By ~ 2

Author(s):

Benjamin Rossi ◽

Lee S Nguyen ◽

Philippe Zimmermann ◽

Faiza Boucenna ◽

Louise Baucher ◽

...

Keyword(s):

Mechanical Ventilation ◽

Single Dose ◽

Propensity Score ◽

Primary Outcome ◽

Invasive Mechanical Ventilation ◽

Multivariable Analysis ◽

Severe Pneumonia ◽

P Value ◽

Retrospective Case

Background. Tocilizumab, a drug targeting interleukin-6 administrated in the right timeframe may be beneficial in coronavirus-disease-2019 (COVID-19). We aimed to assess its benefit, drawing from observations in compassionately treated patients. Methods: In a retrospective case-control study, treatment effect (tocilizumab 400mg, single-dose) was assessed using three statistical methods: propensity-score matching, Cox multivariable survival and inverse probability score weighting (IPSW) analyses. Were included all patients hospitalized with COVID-19, who presented severity criteria with SpO2<96% despite O2-support >6L/min for more than 6 hours. Were excluded patients in critical care medicine department and those under invasive mechanical ventilation. Primary outcome was a composite of mortality and ventilation, with a maximum follow-up of 28 days. Results: 246 patients were included (106 treated by tocilizumab). They were 67.6 +/-15.3 years-old, with 95 (38.5%) women. Delay between first symptoms and inclusion was 8.4 +/-4.5 days. Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-days follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n=168), tocilizumab was associated with fewer primary outcomes (hazard ratio (HR)=0.49 (95% confidence interval (95CI)=0.3-0.81), p-value=0.005). These results were similar in the overall cohort (n=246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR=0.26 (95CI=0.135-0.51, p=0.0001), confirmed by IPSW analysis (p<0.0001). Analyses on mortality with 28-days follow-up yielded similar results. Conclusion: In this retrospective study, tocilizumab single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.

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Adverse cardiovascular complications following prescription of Programmed Cell Death 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) inhibitors

10.1101/2020.12.21.20248648 ◽

2020 ◽

Author(s):

Jiandong Zhou ◽

Gary Tse ◽

Xiansong Wang ◽

Ishan Lakhani ◽

Sharen Lee ◽

...

Keyword(s):

Heart Failure ◽

Cell Death ◽

Programmed Cell Death ◽

Atrial Flutter ◽

Primary Outcome ◽

Cardiovascular Complications ◽

Cardiac Complications ◽

Programmed Death ◽

Programmed Death 1

ABSTRACTBackgroundProgrammed death 1 (PD-1) and programmed death 1 ligand (PD-L1) inhibitors, such as pembrolizumab, nivolumab and atezolizumab, are a major class of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, their use is associated with adverse cardiovascular events. We examined the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors.MethodsPatients receiving PD-1 or PD-L1 inhibitors since their launch up to 31st December 2019 at the Hospital Authority of Hong Kong, without pre-existing cardiac complications were included. The primary outcome was a composite of incident heart failure, acute myocardial infarction (AMI), atrial fibrillation (AF) or atrial flutter with the last follow-up date of 31st August 2020.ResultsA total of 1959 patients were included. Over a median follow-up of 136 days (IQR: 42-279), 320 (16.3%) patients met the primary outcome (heart failure: n=244, AMI: n=38, AF: n=54, atrial flutter: n=6) after PD-1/PD-L1 treatment. Univariate Cox regression showed that age, respiratory diseases, gastrointestinal diseases, a shorter readmission interval and total number of hospitalizations before PD-1/PD-L1 inhibitor prescription, PD-L1 inhibitor use, hyponatraemia, and reduced triglyceride levels were significant predictors of the primary outcome. On multivariate adjustment, older age, a shorter average readmission interval, and a higher number of hospital admissions remained significant predictors. Patients who developed cardiovascular complications had a shorter average readmission interval and a higher number of hospitalizations after PD-1/PD-L1 treatment.ConclusionsCardiovascular complications are found in 16% of patients receiving PD-1 or PD-L1 inhibitors and are associated with more healthcare utilization.

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Left atrial functional assessment and mortality in patients with severe aortic stenosis with sinus rhythm

Cardiovascular Ultrasound ◽

10.1186/s12947-020-00231-0 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

João Ferreira ◽

Valdirene Gonçalves ◽

Patrícia Marques-Alves ◽

Rui Martins ◽

Sílvia Monteiro ◽

...

Keyword(s):

Aortic Valve ◽

Left Atrial ◽

Primary Outcome ◽

Severe Aortic Stenosis ◽

Heart Team ◽

Pump Function ◽

Volumetric Assessment ◽

All Cause Mortality ◽

Echocardiography Laboratory

Abstract Background Aortic valve stenosis (AS) is the most common primary valvular heart disease leading to surgical or percutaneous aortic valve replacement (AVR) in Europe and its prevalence keeps growing. While other risk factors in severe AS are well documented, little is known about the prognostic value of left atrial (LA) function in AS. Our aim is to clarify the relationship between LA function measured at severe AS diagnosis (evaluated by means of volumetric assessment) and all-cause mortality during follow-up. Methods We retrospectively evaluated patients diagnosed with severe AS for the first time at our echocardiography laboratory. We evaluated LA reservoir, conduit and pump function by measuring LA volumes at different timings of cardiac cycle. Treatment strategy was decided according to heart team consensus and patient decision. We divided patients into groups according to terciles of LA reservoir, conduit and pump function. Primary outcome was defined by the occurrence of all-cause mortality during follow-up. Results A total of 408 patients were included in the analysis, with a median follow-up time of 45 months (interquartile range 54 months). 57.9% of patients underwent AVR and 44.9% of patients registered the primary outcome during follow-up. Left atrial emptying fraction (LAEF) was the best LA functional parameter and the best overall parameter in discriminating primary outcome (AUC 0.845, 95%CI 0.81–0.88, P < 0.001). After adjustment for clinical, demographic and echocardiographic variables, cumulative survival of patients with LAEF < 37% and LAEF 37 to 53% relative to patients with LAEF ≥54% remained significantly lower (HR 13.91, 95%CI 6.20–31.19, P < 0.001 and HR 3.40, 95%CI 1.57–7.37, P = 0.002, respectively). After adjustment for AVR, excess risk of LAEF < 37% and LAEF 37 to 53% relative to LAEF ≥54% remained significant (HR 11.71, 95%CI 5.20–26.40, P < 0.001 and HR 3.59, 95%CI 1.65–7.78, P = 0.001, respectively). Conclusions In patients with a first diagnosis of severe AS, LA function, evaluated by means of volumetric assessment, is an independent predictor of all-cause mortality and a more potent predictor of death compared to classical severity parameters. These data can be useful to identify high-risk patients who might benefit of AVR.

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Coronary risk of patients with valvular heart disease: prospective validation of CT-Valve Score

Open Heart ◽

10.1136/openhrt-2020-001380 ◽

2020 ◽

Vol 7 (2) ◽

pp. e001380

Author(s):

Rasmus Bo Hasselbalch ◽

Mia Marie Pries-Heje ◽

Sarah Louise Kjølhede Holle ◽

Thomas Engstrøm ◽

Merete Heitmann ◽

...

Keyword(s):

Heart Disease ◽

Valvular Heart Disease ◽

Primary Outcome ◽

Multislice Ct ◽

Cost Effective ◽

University Hospital ◽

Before And After ◽

History Of ◽

Artery Disease

ObjectiveTo prospectively validate the CT-Valve score, a new risk score designed to identify patients with valvular heart disease at a low risk of coronary artery disease (CAD) who could benefit from multislice CT (MSCT) first instead of coronary angiography (CAG).MethodsThis was a prospective cohort study of patients referred for valve surgery in the Capital Region of Denmark and Odense University Hospital from the 1 February 2015 to the 1 February 2017. MSCT was implemented for patients with a CT-Valve score ≤7 at the referring physician’s discretion. Patients with a history of CAD or chronic kidney disease were excluded. The primary outcome was the proportion of patients needing reevaluation with CAG after MSCT and risk of CAD among the patients determined to be low to intermediate risk.ResultsIn total, 1149 patients were included. The median score was 9 (IQR 3) and 339 (30%) had a score ≤7. MSCT was used for 117 patients. Of these 29 (25%) were reevaluated and 9 (7.7%) had CAD. Of the 222 patients with a score ≤7 that did not receive an MSCT, 14 (6%) had significant CAD. The estimated total cost of evaluation among patients with a score ≤7 before implementation was €132 093 compared with €79 073 after, a 40% reduction. Similarly, estimated total radiation before and after was 608 mSv and 362 mSv, a 41% reduction. Follow-up at a median of 32 months (18–48) showed no ischaemic events for patients receiving only MSCT.ConclusionThe CT-Valve score is a valid method for determining risk of CAD among patients with valvular heart disease. Using a score ≤7 as a cut-off for the use of MSCT is safe and cost-effective.

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Canadian Registry of Electronic Device Outcomes: remote monitoring outcomes in the Abbott battery performance alert—a multicentre cohort

EP Europace ◽

10.1093/europace/euab025 ◽

2021 ◽

Author(s):

Sharath Kumar ◽

Jason Davis ◽

Bernard Thibault ◽

Iqwal Mangat ◽

Benoit Coutu ◽

...

Keyword(s):

Remote Monitoring ◽

Primary Outcome ◽

Electronic Device ◽

Electronic Devices ◽

Cardiac Resynchronization ◽

Device Performance ◽

Cardiac Implantable Electronic Devices ◽

All Cause Mortality ◽

Multicentre Cohort

Abstract Aims Cardiac implantable electronic devices with device advisories have the potential of device malfunction. Remote monitoring (RM) of devices has been suggested to allow the identification of abnormal device performance and permit early intervention. We sought to describe the outcomes of patients with and without RM in devices subject to the Abbott Premature Battery Depletion (PBD) advisory with data from a Canadian registry. Methods and results Patients with an Abbott device subject to the PBD advisory from nine implantable cardioverter defibrillator (ICD) implanting centres in Canada were included in the registry. The use of RM was identified from baseline and follow-up data in the registry. The primary outcome was detection of PBD and all-cause mortality. A total of 2666 patients were identified with a device subject to the advisory. In all, 1687 patients (63.2%) had RM at baseline. There were 487 deaths during follow-up. At a mean follow-up of 5.7 ± 0.7 years, mortality was higher in those without a remote monitor compared with RM at baseline (24.7% vs. 14.5%; P < 0.001). Pre-mature battery depletion was identified in 36 patients (2.1%) with RM vs. 7 (0.7%) without RM (P = 0.004). Time to battery replacement was significantly reduced in patients on RM (median 5 vs. 13 days, P = 0.001). Conclusion The use of RM in patients with ICD and cardiac resynchronization therapy under advisory improved detection of PBD, time to device replacement, and was associated with a reduction in all-cause mortality. The factors influencing the association with mortality are unknown and deserve further study.

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A report on an acute, in-hours, outpatient review clinic with ultrasonography facilities for the early evaluation of general surgical patients

Annals of The Royal College of Surgeons of England ◽

10.1308/rcsann.2016.0164 ◽

2016 ◽

Vol 98 (7) ◽

pp. 468-474 ◽

Cited By ~ 3

Author(s):

TE Pidgeon ◽

U Shariff ◽

F Devine ◽

V Menon

Keyword(s):

Computed Tomography ◽

Primary Outcome ◽

Surgical Patients ◽

Clinic Attendance ◽

Early Evaluation ◽

Admission Rates ◽

Before And After ◽

Age Range ◽

Surgical Clinic

Introduction In 2013 our hospital introduced an in-hours, consultant-led, outpatient acute surgical clinic (ASC) for emergency general surgical patients. In 2014 this clinic was equipped with a dedicated ultrasonography service. This prospective cohort study evaluated this service before and after the introduction of ultrasonography facilities. Methods Data were recorded prospectively for all patients attending the clinic during 2013 and 2014. The primary outcome was patient destination (whether there was follow-up/admission) after clinic attendance. Results The ASC reviewed patients with a wide age range and array of general surgical complaints. In 2013, 186 patients attended the ASC. After the introduction of the ultrasonography service in 2014, 304 patients attended. In 2014, there was a reduction in the proportion of patients admitted to hospital from the clinic (18.3% vs 8.9%, p=0.002). However, the proportion of patients discharged after ASC review remained comparable with 2013 (30.1% in 2013 vs 38.8% in 2014, p=0.051). The proportion of patients undergoing computed tomography (CT) scans also fell (14.0% vs 4.9%, p<0.001). Conclusions The ASC assessed a wide array of general surgical complaints. Only a small proportion required hospital admission. The introduction of an ultrasonography service was associated with a further reduction in admission rates and computed tomography.

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Association of Body Weight Variability with Adverse Cardiovascular Outcomes in Patients with Pre-Dialysis Chronic Kidney Disease

Nutrients ◽

10.3390/nu13103381 ◽

2021 ◽

Vol 13 (10) ◽

pp. 3381

Author(s):

Sang Heon Suh ◽

Tae Ryom Oh ◽

Hong Sang Choi ◽

Chang Seong Kim ◽

Eun Hui Bae ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Body Weight ◽

Kidney Disease ◽

Primary Outcome ◽

Body Weight Gain ◽

Absolute Difference ◽

Composite Outcome ◽

Increased Risk ◽

All Cause Mortality

To investigate the association of body weight variability (BWV) with adverse cardiovascular (CV) outcomes in patient with pre-dialysis chronic kidney disease (CKD), a total of 1867 participants with pre-dialysis CKD from Korean Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) were analyzed. BWV was defined as the average absolute difference between successive values. The primary outcome was a composite of non-fatal CV events and all-cause mortality. Secondary outcomes were fatal and non-fatal CV events and all-cause mortality. High BWV was associated with increased risk of the composite outcome (adjusted hazard ratio (HR) 1.745, 95% confidence interval (CI) 1.065 to 2.847) as well as fatal and non-fatal CV events (adjusted HR 1.845, 95% CI 1.136 to 2.996) and all-cause mortality (adjusted HR 1.861, 95% CI 1.101 to 3.145). High BWV was associated with increased risk of fatal and non-fatal CV events, even in subjects without significant body weight gain or loss during follow-up periods (adjusted HR 2.755, 95% CI 1.114 to 6.813). In conclusion, high BWV is associated with adverse CV outcomes in patients with pre-dialysis CKD.

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Electrical Substrate Ablation for Refractory Ventricular Fibrillation: Results of the AVATAR Study

Circulation Arrhythmia and Electrophysiology ◽

10.1161/circep.120.008868 ◽

2021 ◽

Author(s):

David E. Krummen ◽

Gordon Ho ◽

Kurt S. Hoffmayer ◽

Franz Schweis ◽

Tina Baykaner ◽

...

Keyword(s):

Ventricular Fibrillation ◽

Primary Outcome ◽

Reference Group ◽

Group Versus ◽

Electrical Storm ◽

Antiarrhythmic Drug Therapy ◽

All Cause Mortality ◽

Rapid Pacing ◽

Optimal Treatment Strategy

Background - Refractory ventricular fibrillation (VF) is a challenging clinical entity, for which ablation of triggering premature ventricular complexes (PVCs) is described. When PVCs are infrequent and multifocal, the optimal treatment strategy is uncertain. Methods - We prospectively enrolled consecutive patients presenting with multiple ICD shocks for VF refractory to antiarrhythmic drug therapy, exhibiting infrequent (≤3%), multifocal PVCs (≥3 morphologies). Procedurally, VF was induced with rapid pacing and mapped, identifying sites of conduction slowing and rotation or rapid focal activation. VF electrical substrate ablation (VESA) was then performed. Outcomes were compared against reference patients with VF who were unable or unwilling to undergo catheter ablation. The primary outcome was a composite of ICD shock, electrical storm, or all-cause mortality. Results - VF was induced and mapped in 6 patients (60±10 y, LVEF 46±19%) with ischemic (n=3) and nonischemic cardiomyopathy. An average of 3.3±0.5 sites of localized reentry during VF were targeted for radiofrequency ablation (38.3±10.9 minutes) during sinus rhythm, rendering VF non-inducible with pacing. Freedom from the primary outcome was 83% in the VF ablation group versus 17% in 6 non-ablation reference patients at a median of 1.0 years (IQR 0.5-1.5 years, p=0.046) follow-up. Conclusions - VESA is associated with a reduction in the combined endpoint compared with the non-ablation reference group. Additional work is required to understand the precise pathophysiologic changes which promote VF in order to improve preventative and therapeutic strategies.

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Comparative effects of sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors on new-onset atrial fibrillation and stroke outcomes

10.1101/2021.01.04.21249211 ◽

2021 ◽

Author(s):

Sharen Lee ◽

Jiandong Zhou ◽

Carlin Chang ◽

Tong Liu ◽

Dong Chang ◽

...

Keyword(s):

Diabetes Mellitus ◽

Atrial Fibrillation ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Propensity Score ◽

Lower Risk ◽

Sglt2 Inhibitors ◽

All Cause Mortality ◽

New Onset

AbstractBackgroundSGLT2I and DPP4I are medications prescribed for type 2 diabetes mellitus patients. However, there are few population-based studies comparing their effects on incident atrial fibrillation or ischemic stroke.MethodsThis was a territory-wide cohort study of type 2 diabetes mellitus patients prescribed SGLT2I or DPP4I between January 1st, 2015 to December 31st, 2019 in Hong Kong. Patients with both DPP4I and SGLT2I use and patients with drug discontinuation were excluded. Patients with prior AF or stroke were excluded for the respective analysis. 1:2 propensity-score matching was conducted for demographics, past comorbidities and medications using nearest-neighbor matching method. Cox models were used to identify significant predictors for new onset heart failure (HF) or myocardial infarction (MI), cardiovascular and all-cause mortality.ResultsThe AF-free cohort included 49108 patients (mean age: 66.48 years old [SD: 12.89], 55.32% males) and the stroke-free cohort included 49563 patients (27244 males [54.96%], mean baseline age: 66.7 years old [SD: 12.97, max: 104.6 years old]). After propensity score matching, SGLT2i use was associated with a lower risk of new onset AF (HR: 0.43[0.28, 0.66]), cardiovascular mortality (HR: 0.79[0.58, 1.09]) and all-cause mortality (HR: 0.69[0.60, 0.79]) in the AF-free cohort. It was also associated with a lower risk of new onset stroke (0.46[0.33, 0.64]), cardiovascular mortality (HR: 0.74[0.55, 1.00]) and all-cause mortality (HR: 0.64[0.56, 0.74]) in the stroke-free cohort.ConclusionsThe novelty of our work si that SGLT2 inhibitors are protective against atrial fibrillation and stroke development for the first time. These findings should be validated in other cohorts.

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