Prior Stroke Research Articles

Abstract 4124289: Changes in high-sensitivity cardiac troponin I and associated cardiovascular risk: Analyses From the FOURIER Trial

Background: Circulating high-sensitivity cardiac troponin I (hs-cTnI) is associated with the risk of future cardiovascular (CV) events in stable patients (pts). Data are scarce regarding changes of hs-cTnI in a stable setting. Aims: To study baseline and changes of hs-cTnI in pts with atherosclerotic CV disease (ASCVD), and the association with risk of major CV events. Methods: We measured hs-cTnI (Abbott ARCHITECT) at baseline (BL) and 24 weeks (wks) in 20,718 pts enrolled in a nested biomarker study of the FOURIER trial, which tested the PCSK9i evolocumab vs. placebo in pts with ASCVD on statin and LDL > 70 or non-HDL > 100 mg/dL. The primary endpoint was an adjudicated composite of CV death, MI, stroke, hosp. for unstable angina, or coronary revascularization. The HR (95% CI) across percent-change of hs-cTnI was investigated in pts with quantifiable hs-cTnI at BL and 24 wks (lower limit of quantification (LLOQ) 3.6ng/L) using restricted-cubic splines and Cox-PH models, adjusted for sex, age, LDL at BL, prior MI, randomized treatment, eGFR, DM, HTN, prior HF, and BMI. A Generalized Additive Model was used to predict event rates as a function of hs-cTnI BL and absolute change, flexibly evaluated with a non-linear interaction. All models were based on 3-year follow-up using landmark analysis from 24 wks. Results: Median age was 63 yrs (25 th , 75 th percentiles: 56, 69), 75.5% were male, 86.1% had CAD, 13.7% PAD, and 19.0% a prior stroke. Of these pts, 11,021 (46.8%) had hs-cTnI > LLOQ at BL and 24 wks. The median hs-cTnI at 24 wks was 6.6ng/L (5 th , 25 th , 75 th , 95 th percentiles are: 3.7, 4.7, 11.9, 51.1 ng/L). The absolute event rate of the primary endpoint across hs-cTnI BL and depending on absolute hs-cTnI change to 24 wks is shown in Fig. A . Higher Hs-cTnI BL was associated with higher event rates (p < 0.001). Additionally, absolute reductions and increases of hs-cTnI from BL to 24 wks resulted in reduced and increased event rates, respectively, across hs-cTnI BL . Additionally, relative decrease and increase of hs-cTnI from BL to 24 wks were associated with reduced and increased relative risk, respectively (p for overall effect < 0.001, Fig. B ). Conclusion: Changes in hs-cTnI are associated with the risk of future CV events. Serial measurements of hs-cTnI may aid in reclassification of CV risk and the identification of pts whose CV risk changes with time.

Abstract 4134896: Clinical and Echocardiographic Markers for the Prediction of Incident Atrial Arrhythmias in Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM), in addition to increasing the risk for heart failure and sudden cardiac death, augments the risk for atrial fibrillation (AF) and atrial flutter (AFL). We aimed to identify clinical and echocardiographic risk factors that are predictive of incident AF/AFL in HCM patients. Methods: This retrospective study included 99 HCM patients from University of Chicago without prior AF/AFL, followed for a median of 3.2 years (IQR: 11.5 months-6.9 years). Clinical data were obtained via chart review; echocardiographic findings were obtained using AI software (Us2.ai) with measurements audited by a level III echocardiography reader. Statistical testing included Chi-square/Fisher’s exact (categorical variables) and T-test/Wilcoxon rank sum (continuous variables). Univariate and multivariate Cox regressions assessed predictive value of risk factors for AF/AFL. Results: 18 HCM patients (18%) developed AF/AFL ( Table 1 ). On univariate analysis, older age (HR 1.06, 95%CI 1.02-1.11, p=0.002), hypertension (HR 8.32, 95%CI 1.10-63.20, p=0.04), diabetes (HR 3.90, 95%CI 1.51-10.03, p=0.005), prior stroke (CVA, HR 3.81, 95%CI 1.34-10.86, p=0.012), and NYHA class II-IV (HR 8.48, 95%CI 2.97-24.21, p<0.001) predicted AF/AFL. E/A (p=0.04), E/e’ (p=0.028), MV-A (p=0.022), and LVEF (p=0.02) were also significant predictors ( Figure 1 ). LVEF (HR 0.92, 95%CI 0.87-0.98, p=0.013) remained a significant predictor of AF/AFL on multivariate analysis controlling for age, hypertension, diabetes, CAD, CVA, and NYHA class. Conclusions: Traditional risk factors including age, hypertension, diabetes, CVA, and NYHA class are significant predictors of incident AF/AFL in HCM patients, highlighting the need for comprehensive risk factor evaluation. Even after adjustment for these clinical markers, LVEF independently predicts new AF/AFL in HCM patients, underscoring the importance of routine echocardiographic assessment for risk stratification in this patient population.

Abstract 4119658: Catheter Ablation for Ventricular Arrhythmias in Transthyretin Cardiac Amyloidosis: A Single Center Experience

Background: Transthyretin cardiac amyloidosis (ATTR-CA) carries an elevated risk of developing ventricular arrhythmias (VA) but there remains limited evidence supporting the role of catheter ablation in this population. Purpose: To assess the safety and efficacy of catheter ablation for VA in ATTR-CA. Methods: An electronic database was used to identify all patients suspected of having ATTR-CA who underwent catheter ablation for VA at our institution between January 2010 and December 2023. Patients who did not meet the diagnosis of ATTR-CA and had a negative workup who underwent catheter ablation for ventricular tachycardia (VT) or premature ventricular contractions (PVCs) were used to form a control group matched for age, sex and left ventricular ejection fraction at a ratio of 2:1. Results: 20 controls and 10 cases of ATTR-CA were identified. Examining the two groups at baseline (Table 1), the mean age at index ablation was 67.7±7.0 and 68.6±8.1 years (p=0.359), mean follow-up time was 4.1±3.1 and 4.2±2.6 years (p=0.494), and the proportion of males was 100% and 90% respectively. The ATTR-CA group had a significantly higher proportion of chronic kidney disease (90% vs. 50%, p=0.032) and prior stroke or thrombotic events compared to the control group (50% vs. 10%, p=0.026) with similar CHA 2 DS 2 VASc scores (4.2±1.6 vs. 3.8±1.3, p=0.233). Both groups had comparable left ventricular ejection fraction (41.4%±14% vs. 46.9%±15.2%, p=0.173), VT/PVCs at presentation (40%/60% vs. 25%/75%, p=0.77), use of antiarrhythmics (70% vs. 60%, p=0.592), and high proportion of atrial fibrillation/flutter (70% vs. 90%, p=0.168). Procedural (261.2±101.2 vs. 265.7±125.6 mins, p=0.449) and total energy delivery time (1442.9±1509.1 vs. 1744.6±956.2 secs, p=0.296) was not significantly different in the two groups. Both groups had a significant decrease in PVC burden postablation with a reduction from 26.8% to 3.8% (p=0.024) and from 27.1% to 13.6% (p=0.028) in the ATTR-CA and control group respectively. A downward trend was seen in antitachycardia pacing events for VT postablation in the ATTR-CA (14.7±9.8 vs. 5.3±6.7, p =0.184) and control (193±387.6 vs. 0.67±1.2. p=0.139) groups. No major complications occurred after ablation (Table 2). Mean time to recurrence post-index ablation was similar between both groups (1620.4±483.8 vs. 1498.8±291.4 days, p=0.987, Figure 1). Conclusions: Catheter ablation appears to be safe and effective for VT and PVCs in patients with ATTR-CA.

Abstract 4136632: Impact of Postoperative Atrial Fibrillation on Long-term Clinical Outcomes in Patients after Coronary Artery Bypass Grafting

Background: The impact of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) on long-term clinical outcomes has not been adequately evaluated yet. Methods: Among consecutive 14927 patients who underwent their first coronary revascularization in the CREDO-Kyoto PCI/CABG Registry Cohort-3 (2011-2013), the study population consisted of 1483 patients who underwent CABG after excluding those with prior AF. POAF was defined as newly documented AF during hospitalization for CABG. The primary outcome measure was all-cause death after discharge. The median clinical follow-up was 5.7 (interquartile range, 4.4-6.6) years. Results: POAF was observed in 337 patients (23%). Multivariable logistic regression analysis indicated that age >=75 years (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.24-2.10; P<0.001) and cardiopulmonary bypass (CPB) use (OR, 1.40; 95%CI, 1.09-1.79; P=0.01) were independent predictors of POAF. Of the 1400 patients discharged alive among the study population, the POAF group included more older patients, patients with prior stroke, and patients prescribed beta-blockers and oral anticoagulants than the non-POAF group. The cumulative 5-year incidence of all-cause death was 15.9% in the POAF group and 13.0% in the non-POAF group (Log-rank P=0.38). After adjusting for confounders, the adjusted risk for all-cause death was almost neutral (adjusted HR, 0.96; 95%CI, 0.70-1.31; P=0.81). The cumulative 5-year incidence of stroke was significantly higher in the POAF group than in the non-POAF group (8.0% versus 4.2%; Log-rank P=0.02), and the adjusted risk of stroke in the POAF group relative to the non-POAF group tended to be higher (adjusted HR: 1.58, 95%CI, 0.99-2.53; P=0.057). However, the cumulative 5-year incidence of major bleeding was significantly higher in the POAF group than in the non-POAF group (14.6% versus 10.7%; Log-rank P=0.01). Even after adjusting for confounders, the excess risk of major bleeding in the POAF group was significant (adjusted HR, 1.42; 95%CI, 1.01-2.00; P=0.041). Conclusions: Advanced age and CPB use were associated with POAF occurrence. POAF was not associated with long-term mortality after discharge. However, it tended to be associated with a higher risk for stroke and was associated with a significantly higher risk for major bleeding. Further study would be needed to clarify the appropriate management of POAF after CABG.

Abstract 4121589: Sex differences in Social Determinants of Health and Adverse Outcomes in Atrial Fibrillation: A UK Biobank Study

Background: Beyond the risk of thromboembolic stroke, people with atrial fibrillation (AF) are substantially burdened with a higher incidence of cardiovascular mortality, even among patients treated with anticoagulants. The reasons behind these outcomes are only partially understood. Social determinants of health (SDOH), strong independent predictors of major adverse cardiovascular events (MACE) in several cardiac diseases, may play a role; however, their impact on AF prognosis and the differences in SDOH by sex have been insufficiently explored. Objective: We investigated the sex differences in the association between SDOH and MACE in patients with AF. Methods: Data from the UK Biobank included participants enrolled from 2006 to 2010. An incident AF patient cohort, free of stroke and MI was created. Seventeen SDOH derived from three domains:: socio-economic status, psychosocial factors, and neighborhood/living environment were identified Cox proportional hazards models were used to evaluate the associations of individual SDOH components with the risk of MACE stratified by sex. Covariates including all variables of the CHA 2 DS 2 -VASc Score (Congestive heart failure, Hypertension, Age, Diabetes, prior stroke or transient ischemic attack, Vascular disease and Sex), current use of antiplatelet therapy or anticoagulation, smoking and body mass index. The primary outcome was a composite of MACE (including stroke, transient ischemic attack and arterial thromboembolic event, MI and cardiovascular mortality) and all-cause mortality. Results: A total of 23,113 participants with AF (mean age, 62.44 ± 5.88 years; female sex 39.7%) were included. The composite outcome occurred in 5,151 (22%) of participants over 10-year follow up. In the multivariate adjusted model, several SDOH were independently associated with an increased risk of adverse outcomes. Males showed a broader range of SDOH that were significantly associated with outcomes, including unfavourable economic factors and low social support. Despite females had fewer significant SDOH, education-related factors and local crime rates were significant predictors of adverse outcomes (Figure 1). Conclusions: Adverse SDOHs are associated with a higher risk of MACE and all-cause mortality in AF, with sex-specific variations. These findings underscore the need of incorporating routinely SDOH assessment into clinical practice to more accurately stratify risk and tailor preventive strategies based on sex-specific data.

Abstract 4144520: Glucagon-like Peptide-1 Receptor Agonists for the Primary Prevention of Major Adverse Cardiac Events in Drug-naïve Type 2 Diabetes: A Propensity-score Analysis

Background: The effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RA) as a first-line agent for the primary prevention of major adverse cardiac events (MACE) in obese patients with diabetes mellitus (DM) is unknown. Research Question: Does initial treatment with GLP-1 RA in obese drug-naïve patients with type 2 DM prevent future MACE? Aims: To examine the association between GLP-1 RA treatment and the primary prevention of MACE in drug-naïve type 2 DM patients with obesity. Methods: A retrospective propensity score-matched (PSM) analysis was conducted using the TriNetX Global database. We implemented a new-user design, including adult overweight/obese patients with drug-naive type 2 DM between January 1 st , 2019 and May 1 st , 2023. Patients with prior heart failure (HF), myocardial infarction (MI), coronary revascularization, stroke, or cardiac arrest were excluded. We compared those starting GLP-1 RA versus starting non GLP-1 RA. Medication starting window spans from the first diagnosis to 3 months afterwards. Patients with insulin were excluded if they had any emergency or inpatient encounters during this window. The primary outcome was incident MACE, defined as any death, decompensated HF, MI, cardiac arrest, or ventricular tachycardia/fibrillation, within 5 years of initial drug dispense. Secondary outcomes were individual MACE. Gastrointestinal bleeding was set as a falsification endpoint. Results: Of 1,245,340 patients with A1c <10% and 293,072 patients with A1c ≥10%, 7,483 and 1,563 patients started on GLP-1 RA as a single agent and part of a combined approach, respectively. After PSM, baseline covariates were balanced between the two treatment groups and no significant differences were observed in the falsification endpoint by treatment arm (Figure) . Compared with non-GLP-1 RA, with the exception of sodium-glucose cotransporter-2 (SGLT2i), starting a GLP-1 RA first was associated with a significant reduction in MACCE, primarily driven by reductions in decompensated HF (Figure) . Conclusions: Initiation of a GLP-1 RA as the first agent for obese patients with drug-naïve type 2 DM was associated with a significant reduction in MACE compared to all other diabetes medications, with the exception of SGLT2i.

Abstract 4147617: Depression and the Development of Cardiovascular Disease: Insights from All of Us Research Program

Introduction/Background: Depression is recognized as a risk factor for worse outcomes in patients with cardiovascular disease, but there is limited research on whether individuals with depression have an increased incidence of future cardiovascular disease. Research questions/Hypothesis: Do individuals with depression have an increased incidence of cardiovascular disease? Goals/Aims: This study was conducted to evaluate the association between a diagnosis of depression and the risk of developing future cardiovascular events, to determine whether the treatment of depression should be considered as a primary form of cardiovascular disease prevention. Methods/Approach: We conducted a prospective analysis using the “All Of Us” Research Program dataset. Participants who responded to the historical depression status in the “Personal/Family History Survey” and with linked electronic health records data were considered eligible for this study. We used Cox regression models to calculate the incidence of myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF) and the hazard ratio (HR) of a diagnosis of depression. Models were adjusted for sex, race, age, and prevalent hypertension, diabetes mellitus, hyperlipidemia, and smoking. The survival analysis of the four outcomes was conducted in parallel. We conducted sensitivity analysis by excluding participants with documentation of prior MI, stroke, HF, and/or AF. Results/Data: 100,030 participants were included in this study, with a mean age of 53.2 (standard deviation of 16.5). 68.4% of participants were female, 10% were Hispanic, 9.6% were Black, and 37.1% had a diagnosis of depression. The median follow up time was 3 years. Compared to participants without depression, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.05–1.41), stroke (aHR 1.68, 95% CI 1.06–2.68), HF (aHR 1.28, 95% CI 1.15–1.43), and AF (aHR 1.14, 95% CI 1.02–1.27). In the sensitivity analysis, participants with depression were at risk of developing MI (aHR 1.22, 95% CI 1.03–1.44), stroke (aHR 1.68, 95% CI 1.06–2.68), and HF (aHR 1.31, 95% CI 1.15–1.48) but not AF (aHR 1.12, 95% CI 0.99–1.27). Conclusions: This study indicates that patients with a diagnosis of depression were more likely to develop cardiovascular disease, even if they had no known history of cardiovascular disease. Providers should include the treatment of depression as a part of a holistic approach to cardiovascular disease prevention.

Abstract 4134364: Predicted Low-Density Lipoprotein Cholesterol and Cardiovascular Outcomes Lowering With Inclisiran in Patients With or Without stroke: Insights from SIRIUS in silico trial.

Introduction: Inclisiran, an siRNA, targeting PCSK9 mRNA, reduces LDL-c levels. In SIRIUS in silico trial (NCT05974345), inclisiran was predicted to lower cardiovascular (CV) events in virtual patients with atherosclerotic cardiovascular disease (ASCVD). Research question: This analysis predicted the potential efficacy of inclisiran on CV outcomes in virtual patients with or without prior ischemic stroke (IS). Methods: The SIRIUS trial was conducted using a calibrated and validated knowledge-based mechanistic computational model of ASCVD applied to a virtual population with LDL-C ≥ 70 mg/dL. Each virtual patient was its own control. SIRIUS compared the efficacy of inclisiran vs placebo on top of High Intensity (HI) statin with or without ezetimibe on 3-Point-MACE defined as a composite of time to first occurrence of CV death, nonfatal myocardial infarction (MI) or nonfatal IS over 5 years in patients with or without prior IS. Occurrence of fatal and non-fatal (IS) was also individually assessed in time-to-first-event analyses. Results: Among 204,691 virtual SIRIUS ASCVD patients, 39 371 (19%) had prior IS. At 5 years, the predicted mean percentage reduction in LDL-C with inclisiran as compared to placebo was –49.17% and –49.88% in patients with or without prior IS respectively. Patients with prior IS were at higher risk of 3P-MACE than patients without IS both with placebo and inclisiran (17.01% vs 14.41% with placebo and 13.44% vs 10.83% with inclisiran). However, the predicted rate of 3P-MACE in the inclisiran arm was consistently lower than in the placebo arm for both prior IS and no prior IS (HR 0.78 medium uncertainty and 0.74 low uncertainty respectively). Compared to placebo, inclisiran was also predicted to consistently reduce fatal and non-fatal IS in patients with or without prior IS (5.45% vs 7.22%; HR: 0.75 medium uncertainty and 1.87% vs 2.54%; HR: 0.73 medium uncertainty respectively). Conclusion: SIRIUS provides insights into the potential efficacy of inclisiran on CV events suggesting a substantial 3P-MACE and fatal and non-fatal IS reduction in ASCVD patients including those with prior IS, several years before the availability of results from ongoing outcomes trials (ORION-4, VICTORION-2P).

Increased risk of stroke in non-rheumatic valvular disease associated with antiphospholipid syndrome (APS): a US nationwide study 2017-2019

Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune syndrome characterized by the presence of antiphospholipid autoantibodies, arterial and venous thrombosis, recurrent pregnancy loss and thrombocytopenia. Cardiac manifestations are also common which include coronary artery disease (CAD), non rheumatic valvular heart disorders (NRVHD), myocardial dysfunction, intracardiac thrombi and pulmonary hypertension. Valvular lesions occur likely due to immune complex deposition on the valves, causing fibrosis, calcification and subsequently valvular deformities. Literature review suggests prevalence of NRVHD in APS population is 30% and left sided valves are more involved than right. An increased risk of stroke has also been seen in APS patients with valvular disorders. Purpose Studies report variations in incidence of NRVHD in association with APS. To estimate the prevalence of NRVHD and their correlation with APS, we conducted a retrospective database analysis of hospitalizations across the United States. Additionally we investigated whether this association indicates a increased risk of ischemic stroke in this specific subpopulation. Methods The national inpatient sample (NIS) from 2017-2019 was queried for adult patients (age>18 yrs) admitted with a primary or secondary diagnosis of APS. These patients were stratified for different NRVHD including tricuspid stenosis, tricuspid insufficiency, pulmonary stenosis, pulmonary regurgitation, mitral stenosis, mitral insufficiency (MI), aortic stenosis (AS), and aortic regurgitation. Baseline risk factors and cardiac complications were compared. Multiple regression analysis was performed to study the association of NRVHD with stroke as the primary outcome in the subpopulation of APS hospitalizations. Results A total of 567600 adult patients hospitalized with diagnosis of APS were identified from the NIS 2017-2019 database. Among those, 33,095 had NRVHD with a mean age of 69 years. Of these, prevalence of males was 52.41% compared to females of 47.59%. In the cohort of APS, patients with NRVHD had a higher prevalence of coronary artery disease (43.78% vs 20.41%), diabetes mellitus (30.65% vs 27.56%), prior stroke (10.42% vs 7.78%) than those without valvular disorders. Among the APS population the most prevalent NRVHD were mitral insufficiency (MI), 2.45% and aortic stenosis (AS), 2.13%. In the cohort of NRVHD in APS hospitalizations, the odds of stroke was found to be 1.3 times higher with statistical significance (confidence interval (CI): 1.13-1.48, p <0.001) adjusted for relevant clinical and demographic risk factors such as tobacco abuse, CAD, diabetes mellitus, prior stroke. Conclusion This study shows 6.2% prevalence of NRVHD in APS population, of which MI and AS were common. NRVHD is also associated with higher odds of stroke in APS. Further studies are warranted in identifying the risk of stroke with NRVHD in APS population and emphasizing the need for early detection.

Global burden of high-risk cardiovascular patients without prior myocardial infarction or stroke: VESALIUS-REAL - preliminary results from Germany

Abstract Background Clinical trial data has shown that low-density lipoprotein cholesterol (LDL-C) lowering with PCSK9-inhibitors reduced cardiovascular (CV) endpoints in patients with established atherosclerotic cardiovascular disease (ASCVD). Intervening early in patients with high CV risk prior to myocardial infarction (MI) or stroke, while perceived to be less urgent, may result in larger public health benefits. The effect of evolocumab in this population is investigated in a phase-3 clinical trial (NCT03872401: Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke [VESALIUS-CV]). This observational study examines the global burden of VESALIUS-CV-like population in the REAL-World ("VESALIUS-REAL") in eight regions (Germany, Hong Kong, Japan, South Korea, Sweden, Taiwan, UK and US) using a unified protocol across multiple databases. The multi-database study is ongoing, and the current analysis focuses on characteristics of VESALIUS-CV like patients in Germany. Methods Eligibility criteria are shown in the Figure. Data were obtained from the German Disease Analyzer (2013-2022), a representative claims database from Germany. Criteria were aligned with the clinical trial, and real-world definitions were created using diagnosis and procedure codes. Results A total of 195,621 patients were included in the present analysis (Table). At baseline, the median age was 71 years (Q1-Q3: 64-79) and 48% of patients were women. Approximately two-thirds of patients had atherosclerosis (48.5% had coronary artery disease, 13.8% had cerebrovascular disease and 13.8% had peripheral artery disease) and 33.7% had high-risk diabetes mellitus (DM), defined as DM with microvascular complications or chronic insulin use. The median baseline LDL-C was 139 (Q1-Q3: 113-166) mg/dL [3.6 (2.9 - 4.3) mmol/L] and 110,867 patients (57%) had an LDL-C ≥130 mg/dL (≥3.4 mmol/L). Overall, 69% of VESALIUS-CV like patients were receiving no background LLT. Conclusions Despite having atherosclerosis and/or high-risk DM and LDL-C exceeding target thresholds, a large proportion of VESALIUS-CV like patients were not on any LLT in Germany. Final results from VESALIUS-REAL will be able to report if this treatment gap is also observed in other countries.

Predictors and outcomes of intracranial hemorrhage in 58,000 patients with atrial fibrillation on oral anticoagulation: insights from COMBINE-AF

Abstract Background Among anticoagulated patients with atrial fibrillation (AF), intracranial hemorrhage (ICH) is the leading cause of bleeding-related death and disability. The COMBINE-AF database has patient-level data from four major randomized-controlled trials [ROCKET-AF (rivaroxaban), RE-LY (dabigatran), ENGAGE-TIMI 48 (edoxaban), ARISTOTLE (apixaban)] of direct oral anticoagulants (DOACs) versus warfarin in patients with AF. Purpose/Methods We investigated the rates, predictors, and mortality of ICH in patients randomized to DOAC (rivaroxaban, dabigatran, edoxaban, apixaban) or warfarin. ICH was subclassified as subdural or non-subdural (intracerebral, intraventricular, subarachnoid, epidural). Multivariable Cox models were used to identify predictors of ICH. Frequencies and fatality rates of ICH were calculated and displayed as Kaplan-Meier curves. Results In COMBINE-AF, there were 58,634 patients randomized to either DOAC (n=29,362) or warfarin (n=29,272). The mean age was 70.5 years, 37% were female, and 81% were White. The mean CHA2DS2-VASc score was 2.6, 43% of patients had a history of smoking, 31% had diabetes, and 29% had prior stroke/TIA. After a mean of 32 months, ICH occurred in 593 patients (1.01%, 0.58 per 100-patient years, 95% CI [0.54, 0.63]). The most significant independent predictors of ICH in order of importance were: treatment with warfarin, older age, prior stroke/TIA, enrollment in Asia, antiplatelet use at randomization, and history/risk of falls (Figure 1). Mortality after ICH was 48.4% (287/593 participants), with a majority of deaths (82%) occurring within 30 days of ICH event. Non-subdural ICH was more common than subdural ICH (73% vs 25%) and had a higher risk of death (Figure 2). Participants randomized to DOAC had a lower risk of both subdural and non-subdural ICH than those treated with warfarin; however, mortality rates after ICH were similar regardless of anticoagulant type. Conclusion ICH is an uncommon but devastating complication of oral anticoagulation in patients with atrial fibrillation. The mortality rate following ICH is high, particularly following non-subdural ICH. To reduce the risk of ICH, clinicians should consider using DOACs over warfarin and carefully evaluate the need for antiplatelet therapy, particularly in patients with other significant predictors of ICH such as prior stroke, advanced age, residence in Asia, and history of falls.Predictors of Intracranial Hemorrhage90-Day Mortality after ICH

Anticoagulation status and left atrial appendage occlusion indications in hospitalized cardiology patients with atrial fibrillation: a Hellenic Cardiorenal Morbidity Snapshot (HECMOS) sub-study

Abstract Background Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (NVAF) patients. Left atrial appendage occlusion (LAAC) may be considered for stroke prevention in patients with NVAF and contraindications for long-term anticoagulant treatment. Purpose We aimed to assess the anticoagulation status and LAAC indications in patients with NVAF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Methods HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with poor adherence to anticoagulants, high bleeding risk, previous major bleeding, and previous stroke were considered candidates for LAAC. Results Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA 2 DS 2 - VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA 2 DS 2 -VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA 2 DS 2 -VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA 2 DS 2 -VASc > 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 77 patients with NVAF (53 had only one risk factor, while 22 had two and 2 patients had three concurrent risk factors). In detail, 15 reported poor or no adherence to the anticoagulant therapy, 17 patients had a history of major bleeding, 36 had a prior stroke and 35 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusion Αnticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. Three out of ten AF patients should be screened for LAAC.Anticoagulation by thrombotic riskPotential LAAC candidates

The association of obesity and in-hospital outcomes among patients undergoing ablation for atrial fibrillation: a propensity-score matched analysis

Abstract Background Obesity is a strong risk factor for atrial fibrillation (AF), and it can affect the prognosis of AF. However, the impact of obesity (BMI≥30 kg/m²) on postoperative complications after AF ablation has not been extensively studied. We aimed to evaluate the association of obesity with in-hospital outcomes among patients with AF who ablation procedures. Methods The study utilized the National Inpatient Sample (NIS) database 2016-2020. Patients were divided into obese and non-obese groups and matched with propensity score matching (1:1). This matching involved adjusting for baseline variables (including age, gender, primary expected payer, race, and median household income) and comorbidities (including diabetes, hypertension, hyperlipidemia, history of coronary artery bypass grafting (CABG), chronic kidney disease, hyperthyroidism, cardiomyopathy, prior stroke or transient ischemic attack, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF), heart valve disease, coronary artery disease, chronic obstructive pulmonary disease (COPD), alcohol misuse, anemia, and smoking). Furthermore, a weighted analysis was conducted utilizing weights provided by the NIS, and multivariate logistic regression was used to calculate the odds ratio. Results A total of 29,440 patient with AF who underwent ablation were included. After propensity matching, (8,110 in obese and 8,110 in non-obese group) the baseline characteristics were not significantly different between the two groups. Obesity was independently associated with higher risk of pseudoaneurysm, hematoma, postoperative anemia, acute kidney injury, vasopressor need, mechanical ventilation, pulmonary embolism, and ischemic stroke in patients who underwent ablation for AF (Figure 1). In addition, obese group had significantly higher length of stay (median and IQR 2 [1-3] vs 2 [1-4]) and total charges (median and IQR: 131,248$ [95,303-197,784] vs 143,693$ [102,720-206728]) compared to non-obese group (p<0.001). However, in-hospital mortality was not significantly different between the two groups. Conclusion In patients who underwent AF ablation, obesity is associated with significantly higher risk of post-operative complications, as well as increased LOS and total hospital charges.

Usefulness of left ventricular mechanical dyssynchrony for predicting atrial fibrillation and adverse outcomes following first atrial fibrillation event

Abstract Background Left ventricular mechanical dyssynchrony (LVMD) has shown to predict many cardiovascular outcomes including ventricular arrhythmias. Our hypothesis is that LVMD can reveal early atrial dysfunction. Purpose The aim of this study was to investigate whether LVMD can be used to predict atrial fibrillation (AF) and adverse outcomes following first AF event in individuals from the general population. Methods A total of 3785 individuals (mean age 55±17 years, 57% women) from the general population free of AF, heart failure (HF) and prior stroke had an echocardiographic examination performed including two-dimensional speckle tracking echocardiography. LVMD was calculated as the standard deviation of the regional time-to-peak strain from the three apical views. The primary endpoint was AF, and the secondary endpoint was complicated AF as assessed by the occurrence of either stroke or HF after the diagnosis of AF. Results During a median follow-up of 5 years (interquartile range, 4.4-6.2 years), 142 (4%) individuals were diagnosed with AF, and of these 22 (15%) individuals developed HF or stroke. LVMD was a univariable predictor of AF (per 10ms increase: HR 1.03; 95% CI (1.02-1.05), p<0.001, Figure). The association remained significant even after multivariable adjustment for age, sex, body mass index, diabetes, hypertension, heart rate, previous ischaemic heart disease, systolic blood pressure, diastolic blood pressure, smoking, left ventricular ejection fraction, global longitudinal strain, left atrial volume index (LAVI), and E/e’ (per 10ms increase: HR 1.02; 95% CI (1.00-1.04), p=0.042). LVMD also predicted complicated AF, and the association remained significant even after multivariable adjustment (per 10ms increase: HR 1.05; 95% CI (1.01-1.09), p=0.026). Furthermore, LVMD provided incremental prognostic information over the LAVI with regard to predicting AF (Harrell’s C-statistics 0.66 vs. 0.70, p=0.012). Conclusion In a low-risk general population, LVMD provides prognostic information on the risk of AF. Additionally, LVMD can identify individuals with complicated AF defined as occurrence of either stroke or HF following the diagnosis of incident AF. Furthermore, LVMD provides incremental prognostic information over the LAVI in predicting AF.

Prognostic implications of p2y12 inhibitor pre-treatment in non-st segment elevation acute coronary syndromes undergoing late invasive strategy - a national registry analysis

Abstract Background Current guidelines recommend considering P2Y12 pre-treatment (PreT) in patients (pts) with non-ST segment elevation acute coronary syndrome (NSTE-ACS) expected to undergo a late invasive strategy, based on individual bleeding risk. Purpose Investigate in-hospital morbidity and mortality in NSTE-ACS pts undergoing a late invasive strategy (coronary angiography (CAG) performed >24h post-admission) comparing those receiving P2Y12 inhibitors (P2Y12i) PreT with those who did not. Methods Retrospective multicenter analysis of NSTE-ACS pts from the Portuguese Registry on Acute Coronary Syndromes (ProACS) undergoing a late invasive strategy from October 2010 to October 2023. Exclusion criteria: previous treatment with P2Y12i or anticoagulants; atrial fibrillation. Two cohorts were defined: pts receiving PreT with P2Y12i before undergoing CAG (group 1) and pts without PreT (group 2). Comparative analyses included baseline characteristics, clinical findings, CAG findings and treatment. Primary outcome was in-hospital major adverse cardiovascular events (MACE), a composite of all-cause mortality, re-infarction, stroke and congestive heart failure. The secondary outcome included individual events and major bleeding. Results 3776 pts were included (mean age:66±12 yrs,29% female), 1530 in group 1 and 2246 in group 2. Group 1 had lower prevalence of dyslipidemia (60 vs 66%, p<0.001), prior stroke (7 vs 5%, p=0.003), myocardial infarction (16 vs 21%) and percutaneous coronary intervention (12 vs 15%) (both p=0.001). On admission, there were no differences regarding Killip-Kimball class (class I - 90 vs 90%,p=0.501) and pts in group 1 less frequently had left ventricular disfunction (left ventricular ejection fraction <50% - 20 vs 24%,p=0.032). Group 1 had higher incidence of obstructive CAD (84 vs 77%,p<0.001), more frequently required more than 1 CAG during admission (8 vs 4%,p<0.001), but multivessel disease did not significantly differ (52 vs 52%,p=0.667). Coronary angioplasty was more frequent in group 1 (63 vs 60%,p=0.019) as was coronary artery bypass graft (13 vs 10%,p=0.002). Regarding anti-thrombotics, group 1 had higher prescription rates of clopidogrel (68 vs 56%), aspirin (99 vs 81%), unfractionated heparin (21 vs 8%), enoxaparin (80 vs 56%), but lower of fondaparinux (12 vs 41%) (all p<0.001). There were no differences in the primary outcome (9 vs 9%,p=0.906) and secondary outcomes: in-hospital mortality (1 vs 1%), re-infarction (1 vs 1%), ischemic stroke (1% vs 0,4%) and congestive heart failure (7% vs 8%) (all p>0.05). Group 1 had higher rates of major bleeding (0.8 vs 0.2%, OR 3.48, CI 95% 1.22-9.89, p=0.013). Conclusions In patients with NSTE-ACS undergoing a late invasive strategy, PreT with P2Y12i showed no statistically significant differences in MACE, despite association with higher rates of major bleeding.Baseline characteristicsPrimary and secondary outcomes

Racial and ethnic disparities in the incidence of stroke and mortality in atrial fibrillation: a US nationwide study

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia globally and is associated with increased risks of cardiovascular mortality and ischemic stroke. Prior research has demonstrated racial/ethnic disparities in AF outcomes yet this work has been limited to small cohorts and did not adjust for anticoagulant therapy. Purpose We compared incidence of ischemic stroke and death by race/ethnicity for patients with AF in the Veterans Health Administration (VA), the largest integrated, low-cost, national healthcare system in the US. Methods In this retrospective cohort study we identified those with an outpatient diagnosis of AF and a confirmatory diagnosis ≦ 180 days of their index AF diagnosis enrolled in VA from January 1, 2014 to December 31, 2021, with follow-up for outcomes from the index AF diagnosis date until May 31, 2022. To create a cohort of incident AF cases, we excluded patients with an AF diagnosis or anticoagulant therapy in the 2 years prior to their index AF diagnosis. We also excluded patients with pre-existing valvular heart disease, prior stroke, receiving hospice care or who died within 180 days of index AF diagnosis. We categorized our independent variable as race (i.e., non-Hispanic American Indian / Alaska Native [AI/AN], Asian, Black, or White [reference group]), and ethnicity (i.e., Hispanic). Our primary outcomes were incidence of stroke or death at any point within the study follow-up period. To compare these outcomes by race/ethnicity we conducted a survival analysis, adjusting for anticoagulant use as a time-varying covariate along with sociodemographic factors (age, sex, region, area deprivation index), clinical factors (CHADS2VA2Sc stroke risk and HAS-BLED bleeding risk), and facility type. Results There were 187,080 patients in the final cohort including 0.5% AI/AN, 1% Asian, 9% Black, 4% Hispanic, 85% White; mean age was 73 years. Over a mean study follow-up period of 4.43 years, 65,375 (34.9%) patients died and 24,910 (13.3%) developed stroke. The adjusted hazard ratio [95% CI] for death was lower for Hispanic (0.84 [0.78, 0.91]) and Black (0.94 [0.91, 0.97]) patients than White patients. In contrast, the adjusted hazard ratio for stroke incidence was higher for Black (1.21 [1.16, 1.27]) and Hispanic (1.10 [1.03, 1.17]) patients than White patients. There was no difference observed between AI/AN or Asian and White patients in either outcome. Conclusions In a national cohort of patients with incident AF, we identified significantly higher rates of stroke in Black and Hispanic than White patients even controlling for myriad factors including anticoagulant use. Conversely, racial/ethnic disparities in mortality appear to be eliminated in VA, counter to prior data. Understanding the factors, beyond anticoagulation, driving disparities in stroke outcomes and identifying factors reducing mortality among minority groups is critical to improving overall AF care in the largest integrated US health system.Adjusted Hazard Ratios of Study Outcomes

Pathogenic cardiomyopathy gene variants inform prognosis in atrial fibrillation: results from exome sequencing in over 17,000 patients in TIMI trials

Abstract Background Rare genetic variants in cardiomyopathy genes are associated with risk of atrial fibrillation (AF), even in the absence of overt ventricular dysfunction. Data on clinical outcomes for rare genetic variant carriers among patients with AF remain sparse. Purpose We aimed to study the prognostic implication of rare pathogenic/likely pathogenic (PLP) variants for dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with AF from large, well-phenotyped randomized clinical trials. Methods and results Rare variants were called using exome sequencing data in 5 large clinical trials from the TIMI study group (ENGAGE-AF, FOURIER, SAVOR, PEGASUS, DECLARE). PLP variants for cardiomyopathy were identified using phenotype- and gene-specific curation of protein-truncating variants and high-confidence variant classifications from the ClinVar database. In 17,190 patients with a history of AF, we identified 421 (2.4%) PLP variant carriers (age 67±10, 35% women) and 16,769 (97.6%) pts without PLP variants (age 70±9, 36% women). Among these individuals, we identified 265 DCM carriers (1.5%), 106 (0.6%) HCM carriers and 54 (0.3%) ARVC carriers. In this cohort, 9,275 (54%) had a history of heart failure (HF) and 2,991 (17.4%) prior ischemic stroke. Over 2.5 years median follow-up, 1,365 pts (7.9%) were hospitalized for HF, 599 (3.5%) had an ischemic stroke, and 1147 (6.7%) died of cardiovascular causes. In logistic regression analyses adjusting for age, sex, trial, and principal components of ancestry, PLP variants were significantly associated with a history of HF (OR 1.66, p<0.0001), most notably for DCM variants (OR 1.97, 1.48-2.62, p<0.0001). PLP variants were independently associated with incident HF admissions (adj HR 1.75, 1.39-2.29, p<0.0001), most notably for HCM (adj HR 2.59, 1.68-3.99, p<0.0001) and ARVC variants (adj HR 2.50, 1.34-4.66, p=0.004). The increased risk of HF admissions remained consistent in patients with (adj HR 1.49, 1.11-2.00, p=0.009) and those without (adj HR 1.88, 1.00-3.54, p=0.049) a history of HF. PLP variants were also associated with higher risk of cardiovascular death (adj HR 1.46, 1.06-2.02, p=0.02), most notably for DCM variants (adj HR 1.77, 1.21-2.58, p=0.003). In contrast, PLP variants were not associated with history of ischemic stroke at baseline (adj OR 0.99, p=0.96) nor with incident ischemic stroke (adj HR 0.95, p=0.84). Conclusion In patients with AF, rare cardiomyopathy gene variants are associated with increased risks of HF and of cardiovascular death, but not stroke. These results, collected from large well-phenotyped randomized clinical trials, demonstrate an important prognostic implication for rare genetic variants for CMP in pts with AF.

Comparison of Lp(a) assessment in patients with atherosclerotic cardiovascular disease between office-based cardiologists and general practitioners

Abstract Background Elevated lipoprotein(a) (Lp(a)) levels are a major risk factor that contribute to the development of ASCVD. Different guidelines for the treatment of patients with hypercholesterolemia are available in Germany. The German Cardiac Society recognized the 2019 ESC/EAS guideline for the management of dyslipidemia and endorses the measurement of Lp(a) at least once in a lifetime to identify those with very high inherited Lp(a) levels >180 mg/dL (>430 nmol/L) . The Nationale Versorgungsleitlinie, however, does not recommend testing of Lp(a). Methods and Objectives LipidSnapshot is a joint research project consisting of two parts. Part 1 is a prospective, non-interventional multicenter research project at office-based cardiologists (OBCs). Data from 1500 adults with known coronary artery disease, peripheral artery disease, prior myocardial infarction and/or ischemic stroke are collected from selected 49 OBCs. The second part is a retrospective, aggregated analysis of anonymous electronic medical records of 82.375 adult outpatient ASCVD patients documented by general practices (GPs) obtained from the IQVIA Disease Analyzer (note: 54% do not provide information on Lp(a) data to IQVIA). Availability of Lp(a) tests and lipid-lowering therapies (LLTs) in ASCVD patients with available LDL-C values within a 12-month period (July 2022-June 2023) were assessed. One of the objectives of LipidSnapshot is to compare the proportion of Lp(a) assessments in ASCVD patients documented by OBCs and GPs and to evaluate gender-, age- and LLTs-related differences in Lp(a) availability in patients documented by OBCs compared to GPs. Results Patients treated by OBCs were on average 72.4 (standard deviation (SD) 10.0) years old and 75.8 % were male while patients in the IQVIA dataset were on average 73.0 (SD 13.2) years old and 60.5% were male. The age distribution was comparable between both specialties. OBCs documented Lp(a) in 20.3% of their ASCVD patients, while only 3.0% of ASCVD patients documented by GPs had Lp(a) values documented. The testing rates in male and female patients were comparable between both specialties (OBC: 19.5 vs. 22.9%; GPs: 3.4 vs. 2.5%). For both specialties, Lp(a) testing rate was higher in younger patients compared to older patients (Table 1) and in patients treated with PCSK9-inhibitors (monoclonal antibodies, inclisiran), either as monotherapy or in combination with statins and/or other LLTs (ezetimibe, bempedoic acid, bile acid sequestrants) (Table 2). Conclusion The first snapshot revealed differences in healthcare provision of GPs compared to selected OBCs with lower rates of identification of higher risk patients treated by GPs in Germany.Age-related differences in Lp(a)LLT-related differences in Lp(a)

Prediction of cardiovascular risk in patients type 2 diabetes using the SCORE2-Diabetes risk score

Abstract Background/Introduction The SCORE2-Diabetes risk score was developed to predict the risk of cardiovascular events (CV-death, non-fatal MI and non-fatal stroke) in patients with T2DM without known cardiovascular disease. Current ESC guidelines recommend the use of this risk score to tailor treatment strategies in this population. Purpose We sought to determine whether the SCORE2-Diabetes risk score was able to appropriately stratify an international cohort of patients from recent cardiovascular clinical outcomes trials. Furthermore, we sought to determine the accuracy and precision of the model including in patients with and without known cardiovascular disease. Methods Patients from 4 randomized cardiovascular outcome trials (DEVOTE, LEADER, PIONEER-6, SUSTAIN-6) were included (n=23,464). Mean follow-up was 2.6 years and outcomes were adjudicated. The SCORE2-Diabetes risk score was calculated using the uncalibrated version which does not account for risk-region. Patients were stratified into low (<5%), moderate (5-<10%), high (10-<20%), and very high risk (≥20%) groups. The SCORE2-Diabetes risk predication model was designed to predict 10-year risk; however, given the mean follow-up from the cohort, outcomes were reported at 36 months. The Brier score, which evaluates estimated risk, and c-index, which evaluates the ability to discriminate between participants, were used to evaluate the precision of the risk score. We further compared the risk score with an estimated risk of MACE calculated using a cause specific Cox model that accounts for competing risk. Results Most patients in the cohort did not have prior myocardial infarction or stroke (57.4%, n=13,467). The SCORE2-Diabetes risk score was able to stratify patients into low, moderate, high, and very high risk cohorts (Figure 1). Observed cardiovascular events at 36 months were higher than the SCORE2-Diabetes risk score predicted (Table 1). The risk score, when included in a regression model, independently predicted cardiovascular death, myocardial infarction, or stroke (HRadj 1.03, p<0.001) and non-cardiovascular death (HRadj 1.05, p<0.001). Including the score in models with only age and sex improved the discrimination and performance of the model. The c-index for the risk score in the overall cohort was 0.62 and was 0.66 in the cohort without known cardiovascular disease. When using the Brier score to evaluate the utility of the model, the Brier score of the SCORE2-D model was 0.08 which is no different than a null model which assumes a baseline risk of 10% in all patients. Conclusion In a cohort of patients that was older, more geographically diverse, and at higher risk of cardiovascular events, the SCORE2-D risk score appropriately stratified patients into categories of risk. However, the overall risk prediction underestimated the risk of cardiovascular events and the discrimination of the risk score was modest.Figure:CV events over timeTable:CV events by risk group

Body mass index and clinical outcomes in patients with diabetes and stable coronary artery disease in THEMIS

Abstract Background Physiologic changes due to extremes of body weight may affect the efficacy and tolerability of antiplatelet treatment. However, it remains unclear whether the risks and benefits of intensified antiplatelet therapy among patients with diabetes and stable coronary artery disease (CAD) are affected by body mass index (BMI). Purpose To assess the relationship between baseline BMI and major adverse cardiovascular (CV) events, and to determine if the effects of ticagrelor vs. placebo varied across the BMI spectrum, in patients with diabetes and stable CAD. Methods THEMIS was a randomized, controlled trial of 19,220 individuals aged ≥50 years with type 2 diabetes and stable CAD, randomly allocated to ticagrelor or placebo on top of aspirin. Patients with a prior myocardial infarction (MI) or stroke, or already on dual antiplatelet therapy, were excluded. The primary efficacy outcome was a composite of CV death, MI, or stroke. The primary safety outcome was TIMI major bleeding. We examined prognostic implications of BMI using 1) restricted cubic splines for the overall trends with outcomes; 2) Cox regression models with predefined BMI intervals (<25 kg/m2, 25-29.9 kg/m2, and ≥30 kg/m2) adjusted for demographic, clinical, and laboratory variables; and 3) Cox regression models for the effects of ticagrelor vs. placebo on outcomes across the spectrum of BMI values (test for interaction). A two-sided P-value <0.01 was considered statistically significant to control the overall chance of type I errors. Results BMI was available in 19,202 (99.9%) participants, with a median of 29 kg/m2 (interquartile range: 26-33). A total of 3352 (17.5%) individuals had a BMI <25 kg/m2, 7644 (39.8%) had a BMI 25-29.9 kg/m2, and 8206 (42.7%) had a BMI ≥30 kg/m2. Median follow-up was 39.9 months (range 0-57), with 1554 primary efficacy events and 306 primary safety events occurring over the course of the study. BMI was not associated with the primary efficacy or safety outcome, or with their individual components. However, BMI was significantly associated with hospitalization for heart failure (HHF) (BMI <25 kg/m2: reference; hazard ratio [HR] for BMI 25-29.9 kg/m2: 1.07, 95% confidence interval [CI], 0.82 to 1.40; HR for BMI ≥30 kg/m2: 1.41, 95% CI, 1.07 to 1.84) and with the composite of HHF or CV death (comparable estimates) after multivariable adjustment (Figure). BMI was also significantly, positively associated with serious adverse events (BMI <25 kg/m2: reference; HR for BMI 25-29.9 kg/m2: 0.99, 95% CI, 0.93 to 1.06; HR for BMI ≥30 kg/m2: 1.20, 95% CI, 1.12 to 1.29). BMI did not modify the risks and benefits of ticagrelor vs. placebo. Conclusions BMI was independently associated with the risk of HHF and the composite of HHF or CV death, but not with other efficacy or safety outcomes, in patients with stable CAD and type 2 diabetes. Ticagrelor was of similar benefit on the primary efficacy outcome vs. placebo across the full range of BMI.