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Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head clinical trials., Objectives: The aim of this study was to compare the cardiovascular effectiveness of SGLT2is, GLP-1 RAs, dipeptidyl peptidase-4 inhibitors (DPP4is), and clinical sulfonylureas (SUs) as second-line antihyperglycemic agents in T2DM., Methods: Across the LEGEND-T2DM (Large-Scale Evidence Generation and Evaluation Across a Network of Databases for Type 2 Diabetes Mellitus) network, 10 federated international data sources were included, spanning 1992 to 2021. In total, 1,492,855 patients with T2DM and cardiovascular disease (CVD) on metformin monotherapy were identified who initiated 1 of 4 second-line agents (SGLT2is, GLP-1 RAs, DPP4is, or SUs). Large-scale propensity score models were used to conduct an active-comparator target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, on-treatment Cox proportional hazards models were fit for 3-point MACE (myocardial infarction, stroke, and death) and 4-point MACE (3-point MACE plus heart failure hospitalization) risk and HR estimates were combined using random-effects meta-analysis., Results: Over 5.2 million patient-years of follow-up and 489 million patient-days of time at risk, patients experienced 25,982 3-point MACE and 41,447 4-point MACE. SGLT2is and GLP-1 RAs were associated with lower 3-point MACE risk than DPP4is (HR: 0.89 [95% CI: 0.79-1.00] and 0.83 [95% CI: 0.70-0.98]) and SUs (HR: 0.76 [95% CI: 0.65-0.89] and 0.72 [95% CI: 0.58-0.88]). DPP4is were associated with lower 3-point MACE risk than SUs (HR: 0.87; 95% CI: 0.79-0.95). The pattern for 3-point MACE was also observed for the 4-point MACE outcome. There were no significant differences between SGLT2is and GLP-1 RAs for 3-point or 4-point MACE (HR: 1.06 [95% CI: 0.96-1.17] and 1.05 [95% CI: 0.97-1.13])., Conclusions: In patients with T2DM and CVD, comparable cardiovascular risk reduction was found with SGLT2is and GLP-1 RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of SGLT2is and GLP-1 RAs should be prioritized as second-line agents in those with established CVD., Competing Interests: Funding Support and Author Disclosures This study was partially funded through National Institutes of Health grants R01 HL167858, K23 HL153775, R01 LM006910, R01 HG006139, and R01 HL169954 and the U.S. Department of Veterans Affairs under the research priority to “Put VA Data to Work for Veterans” (VA ORD 22-D4V). The funders had no role in the design and conduct of the protocol; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Dr Khera is an associate editor at JAMA; and has received support from the National Heart, Lung, and Blood Institute of the National Institutes of Health (awards R01 HL167858 and K23 HL153775) and the Doris Duke Charitable Foundation (award 2022060); has received research support, through Yale University, from Bristol Myers Squibb, Novo Nordisk, and BridgeBio; is a coinventor of U.S. provisional patent applications WO2023230345A1, US20220336048A1, 63/346,610, 63/428,569, 63/484,426, 63/508,315, 63/580,137, 63/606,203, 63/619,241, and 63/562,335, unrelated to the present work; and is a cofounder of Evidence2Health and Ensight-AI, precision health platforms to improve evidence-based cardiovascular care and cardiovascular diagnostics. Dr DuVall has received grants from Alnylam Pharmaceuticals, AstraZeneca Pharmaceuticals, Biodesix, Celgene, Cerner Enviza, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis International, and Parexel International through the University of Utah or the Western Institute for Veteran Research (outside the submitted work). Dr Man has received support from the C.W. Maplethorpe Fellowship, the National Institute of Health Research, European Commission Framework Horizon 2020, the Hong Kong Research Grant Council, and the Innovation and Technology Commission of the Hong Kong Special Administration Region Government outside the submitted work). Dr Morales is supported by a Wellcome Trust Clinical Research Fellowship (214588/Z/18/Z). In the past 3 years, Dr Krumholz has received expenses and/or personal fees from UnitedHealth, Element Science, Aetna, Reality Labs, Tesseract/4Catalyst, F-Prime, the Siegfried and Jensen Law Firm, the Arnold and Porter Law Firm, and the Martin/Baughman Law Firm; is a cofounder of Refactor Health, HugoHealth, and Ensight-AI; and is associated with contracts, through Yale New Haven Hospital, from the Centers for Medicare and Medicaid Services and, through Yale University, from Johnson & Johnson. Dr You is chief technology officer of PHI Digital Healthcare. Dr Ross has received research support through Yale University from Johnson & Johnson to develop methods of clinical trial data sharing, from the Food and Drug Administration for the Yale-Mayo Clinic Center for Excellence in Regulatory Science and Innovation program (grant U01 FD005938), from the Agency for Healthcare Research and Quality (grant R01 HS022882), and from Arnold Ventures; has received research support from the Medical Device Innovation Consortium as part of the National Evaluation System for Health Technology and from the National Heart, Lung, and Blood Institute of the National Institutes of Health (grants R01 HS025164 and R01 HL144644); and was an expert witness at the request of the relator’s attorneys, the Greene Law Firm, in a qui tam suit alleging violations of the False Claims Act and Anti-Kickback Statute against Biogen that was settled September 2022. Dr Thangaraj is a coinventor on provisional patent 63/606,203, unrelated to the present work, and is funded by grant 5T32 HL155000-03. Ms Blacketer, Dr Ostropolets, and Dr Ryan are employees of Johnson & Johnson. Dr Schuemie is an employee and shareholder of Johnson & Johnson. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. All rights reserved.)

Aims: Despite notable population differences in high-income and low- and middle-income countries (LMICs), national guidelines in LMICs often recommend using US-based cardiovascular disease (CVD) risk scores for treatment decisions. We examined the performance of widely used international CVD risk scores within the largest Brazilian community-based cohort study (Brazilian Longitudinal Study of Adult Health, ELSA-Brasil)., Methods: All adults 40-75 years from ELSA-Brasil (2008-2013) without prior CVD who were followed for incident, adjudicated CVD events (fatal and non-fatal MI, stroke, or coronary heart disease death). We evaluated 5 scores-Framingham General Risk (FGR), Pooled Cohort Equations (PCEs), WHO CVD score, Globorisk-LAC and the Systematic Coronary Risk Evaluation 2 score (SCORE-2). We assessed their discrimination using the area under the receiver operating characteristic curve (AUC) and calibration with predicted-to-observed risk (P/O) ratios-overall and by sex/race groups., Results: There were 12 155 individuals (53.0±8.2 years, 55.3% female) who suffered 149 incident CVD events. All scores had a model AUC>0.7 overall and for most age/sex groups, except for white women, where AUC was <0.6 for all scores, with higher overestimation in this subgroup. All risk scores overestimated CVD risk with 32%-170% overestimation across scores. PCE and FGR had the highest overestimation (P/O ratio: 2.74 (95% CI 2.42 to 3.06)) and 2.61 (95% CI 1.79 to 3.43)) and the recalibrated WHO score had the best calibration (P/O ratio: 1.32 (95% CI 1.12 to 1.48))., Conclusion: In a large prospective cohort from Brazil, we found that widely accepted CVD risk scores overestimate risk by over twofold, and have poor risk discrimination particularly among Brazilian women. Our work highlights the value of risk stratification strategies tailored to the unique populations and risks of LMICs., Competing Interests: Competing interests: RK is an Associate Editor at JAMA. In addition to the funding listed above, he also receives research support, through Yale, from Bristol-Myers Squibb, Novo Nordisk and BridgeBio. He is a coinventor of Pending Patent Applications WO2023230345A1, US20220336048A1, 63/346 610, 63/484 426, 63/508 315, 63/580 137, 63/606 203, 63/619 241 and 63/562 335, unrelated to current work. He is also a co-founder of Evidence2Health and Ensight-AI, both representing precision health platforms to improve evidence-based cardiovascular care. The other authors declare no conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Despite efforts to improve the quality of care for patients with atherosclerotic cardiovascular disease (ASCVD), it is unclear whether the US has made progress in reducing racial and ethnic differences in utilization of guideline-recommended therapies for secondary prevention., Objective: To evaluate 21-year trends in racial and ethnic differences in utilization of guideline-recommended pharmacological medications and lifestyle modifications among US adults with ASCVD., Design, Setting, and Participants: This cross-sectional study includes data from the National Health and Nutrition Examination Survey between 1999 and 2020. Eligible participants were adults aged 18 years or older with a history of ASCVD. Data were analyzed between March 2022 and May 2023., Exposure: Self-reported race and ethnicity., Main Outcome and Measures: Rates and racial and ethnic differences in the use of guideline-recommended pharmacological medications and lifestyle modifications., Results: The study included 5218 adults with a history of ASCVD (mean [SD] age, 65.5 [13.2] years, 2148 women [weighted average, 44.2%]), among whom 1170 (11.6%) were Black, 930 (7.7%) were Hispanic or Latino, and 3118 (80.7%) were White in the weighted sample. Between 1999 and 2020, there was a significant increase in total cholesterol control and statin use in all racial and ethnic subgroups, and in angiotensin-converting enzyme inhibitor (ACEI) and angiotensin receptor blocker (ARB) utilization in non-Hispanic White individuals and Hispanic and Latino individuals (Hispanic and Latino individuals: 17.12 percentage points; 95% CI, 0.37-37.88 percentage points; P = .046; non-Hispanic White individuals: 12.14 percentage points; 95% CI, 6.08-18.20 percentage points; P < .001), as well as smoking cessation within the Hispanic and Latino population (-27.13 percentage points; 95% CI, -43.14 to -11.12 percentage points; P = .002). During the same period, the difference in smoking cessation between Hispanic and Latino individuals and White individuals was reduced (-24.85 percentage points; 95% CI, -38.19 to -11.51 percentage points; P < .001), but racial and ethnic differences for other metrics did not change significantly. Notably, substantial gaps persisted between current care and optimal care throughout the 2 decades of data analyzed. In the period of 2017 to 2020, optimal regimens were observed in 47.4% (95% CI, 39.3%-55.4%), 48.7% (95% CI, 36.7%-60.6%), and 53.0% (95% CI, 45.6%-60.4%) of Black, Hispanic and Latino, and White individuals, respectively., Conclusions and Relevance: In this cross-sectional study of US adults with ASCVD, significant disparities persisted between current care and optimal care, surpassing any differences observed among demographic groups. These findings highlight the critical need for sustained efforts to bridge these gaps and achieve better outcomes for all patients, regardless of their racial and ethnic backgrounds.

Importance: Wearable devices may be able to improve cardiovascular health, but the current adoption of these devices could be skewed in ways that could exacerbate disparities., Objective: To assess sociodemographic patterns of use of wearable devices among adults with or at risk for cardiovascular disease (CVD) in the US population in 2019 to 2020., Design, Setting, and Participants: This population-based cross-sectional study included a nationally representative sample of the US adults from the Health Information National Trends Survey (HINTS). Data were analyzed from June 1 to November 15, 2022., Exposures: Self-reported CVD (history of heart attack, angina, or congestive heart failure) and CVD risk factors (≥1 risk factor among hypertension, diabetes, obesity, or cigarette smoking)., Main Outcomes and Measures: Self-reported access to wearable devices, frequency of use, and willingness to share health data with clinicians (referred to as health care providers in the survey)., Results: Of the overall 9303 HINTS participants representing 247.3 million US adults (mean [SD] age, 48.8 [17.9] years; 51% [95% CI, 49%-53%] women), 933 (10.0%) representing 20.3 million US adults had CVD (mean [SD] age, 62.2 [17.0] years; 43% [95% CI, 37%-49%] women), and 5185 (55.7%) representing 134.9 million US adults were at risk for CVD (mean [SD] age, 51.4 [16.9] years; 43% [95% CI, 37%-49%] women). In nationally weighted assessments, an estimated 3.6 million US adults with CVD (18% [95% CI, 14%-23%]) and 34.5 million at risk for CVD (26% [95% CI, 24%-28%]) used wearable devices compared with an estimated 29% (95% CI, 27%-30%) of the overall US adult population. After accounting for differences in demographic characteristics, cardiovascular risk factor profile, and socioeconomic features, older age (odds ratio [OR], 0.35 [95% CI, 0.26-0.48]), lower educational attainment (OR, 0.35 [95% CI, 0.24-0.52]), and lower household income (OR, 0.42 [95% CI, 0.29-0.60]) were independently associated with lower use of wearable devices in US adults at risk for CVD. Among wearable device users, a smaller proportion of adults with CVD reported using wearable devices every day (38% [95% CI, 26%-50%]) compared with overall (49% [95% CI, 45%-53%]) and at-risk (48% [95% CI, 43%-53%]) populations. Among wearable device users, an estimated 83% (95% CI, 70%-92%) of US adults with CVD and 81% (95% CI, 76%-85%) at risk for CVD favored sharing wearable device data with their clinicians to improve care., Conclusions and Relevance: Among individuals with or at risk for CVD, fewer than 1 in 4 use wearable devices, with only half of those reporting consistent daily use. As wearable devices emerge as tools that can improve cardiovascular health, the current use patterns could exacerbate disparities unless there are strategies to ensure equitable adoption.