Search

Background: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known., Objectives: The authors sought to determine which antithrombotic regimen best balances safety and efficacy., Methods: AUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y 12 inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint., Results: A total of 4,614 patients were enrolled. All patients were treated with a P2Y 12 inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death., Conclusions: In patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y 12 inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; NCT02415400)., Competing Interests: Funding Support and Author Disclosures The AUGUSTUS study and this analysis were funded by Bristol Myers Squibb and Pfizer. Dr Berwanger has received research grants from AstraZeneca, Pfizer, Bayer, Amgen, Novartis, Servier, and Boehringer Ingelheim. Dr Fanaroff has received research grants from the American Heart Association and National Institutes of Health; and has received consulting fees from Abbott Laboratories. Dr Granger has received research grants from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Armetheon, AstraZeneca, U.S. Food and Drug Administration, GlaxoSmithKline, The Medicines Company, Medtronic Foundation, Medtronic Inc, and Novartis; and has received consulting fees from Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Abbvie, Armetheon, AstraZeneca, Eli Lilly, Gilead, GlaxoSmithKline, Hoffmann-La Roche, The Medicines Company, National Institutes of Health, Novartis, Sirtex, Verseon, Apple, Medscape, LLC, Merck, Novo Nordisk, Roche Diagnostics, and Rho Pharmaceuticals. Dr Mehran has received institutional research grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb/Sanofi, CSL Behring, Eli Lilly/Daiichi-Sankyo, Medtronic, Novartis, and OrbusNeich; has received consulting fees from Boston Scientific, Abbott Vascular, Medscape, Siemens Medical Solutions, Roivant Sciences Inc, and Sanofi; has consulted (no fees) for Regeneron Pharmaceuticals Inc; has received institutional consulting fees from Abbott Vascular, Spectranetics/Phillips/Volcano Corporation, Bristol Myers Squibb, Novartis, and Watermark Research; is an executive committee member for Janssen Pharmaceuticals and Bristol Myers Squibb; and has <1% equity in Claret Medical and Elixir Medical. Dr Aronson is an employee of Bristol Myers Squibb. Dr Windecker has received institutional research and educational grants from Abbott, Amgen, Bayer, Bristol Myers Squibb, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. Dr Goodman has received research grant support and/or speaker/consulting honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo, Eli Lilly, Esperion, Fenix Group International, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, Janssen/Johnson and Johnson, Luitpold Pharmaceuticals, Matrizyme, Merck, Novartis, Novo Nordisk A/C, Pfizer, Regeneron, Sanofi, Servier, Tenax Therapeutics, Heart and Stroke Foundation of Ontario/University of Toronto, Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Duke Clinical Research Institute, and PERFUSE. Dr Alexander has received research grants from Bristol Myers Squibb, Boehringer Ingelheim, AstraZeneca, CryoLife, CSL Behring, U.S. Food and Drug Administration, National Institutes of Health, Sanofi, and VoluMetrix; and has received consulting fees from Pfizer, Bristol Myers Squibb, AbbVie Pharmaceuticals, CSL Behring, Novo Nordisk, Portola Pharmaceuticals, Quantum Genomics, Teikoku Pharmaceuticals, VA Cooperative Studies, and Zafgen. Dr Lopes has received research grants or contracts from Amgen, Bristol Myers Squibb, GlaxoSmithKline, Medtronic, Pfizer, and Sanofi; has received funding for educational activities or lectures from Pfizer, Daiichi-Sankyo, and Novo Nordisk; and has received funding for consulting or other services from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, and Novo Nordisk. 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. Published by Elsevier Inc. All rights reserved.)

Background: In patients with or at risk for atherosclerotic vascular disease, statins reduce the incidence of major adverse cardiovascular events, but the majority of US adults with an indication for statin therapy are not prescribed statins at guideline-recommended intensity. Clinicians' limited time to address preventative care issues is cited as one factor contributing to gaps in statin prescribing. Centralized pharmacy services can fulfill a strategic role for population health management through outreach, education, and statin prescribing for patients at elevated ASCVD risk, but best practices for optimizing referrals of appropriate patients are unknown., Study Design and Objectives: SUPER LIPID (NCT05537064) is a program consisting of two pragmatic clinical trials testing the effect of nudges in increasing referrals of appropriate patients to a centralized pharmacy service for lipid management, conducted within 11 primary care practices in a large community health system. In both trials, patients were eligible for inclusion if they had an assigned primary care provider (PCP) in a participating practice and were not prescribed a high- or moderate-intensity statin despite an indication, identified via an electronic health record (EHR) algorithm. Trial #1 was a stepped wedge trial, conducted at a single practice with randomization at the PCP level, of an interruptive EHR message that appeared during eligible patients' visits and facilitated referral to the pharmacy service. For the first 3 months, no PCPs received the message; for the second 3 months, half were randomly selected to receive the message; and for the last 3 months, all PCPs received the message. Trial #2 was a cluster-randomized trial conducted at 10 practices, with randomization at the practice level. Practices were randomized to usual care or to have eligible patients automatically referred to centralized pharmacy services via a referral order placed in PCPs EHR inboxes for co-signature. In both trials, when a patient was referred to centralized pharmacy services, a pharmacist reviewed the patient's chart, contacted the patient, and initiated statin therapy if the patient agreed. The primary endpoint of both trials was the proportion of patients prescribed a statin; secondary endpoints include the proportion of patients prescribed a statin at guideline-recommended intensity, the proportion of patients filling a statin prescription, and serum low-density lipoprotein level., Conclusions: SUPER LIPID is a pair of pragmatic clinical trials assessing the effectiveness of two strategies to encourage referral of appropriate patients to a centralized pharmacy service for lipid management. The trial results will develop the evidence base for simple, scalable, EHR-based strategies to integrate clinical pharmacists into population health management and increase appropriate statin prescribing., Clinical Trial Registration: clinicaltrials.gov; NCT05537064., Competing Interests: Conflicts of interest Dr. Fanaroff reports a career development grant from the American Heart Association. Dr. Adusumalli is an employee of CVS Health. Dr. Volpp is a co-owner of a behavioral economics consulting firm, VAL Health and receives unrelated research funding from Independence Blue Cross and the American Heart Association. All other authors report no relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Randomized clinical trials (RCTs) often suffer from a lack of representation from historically marginalized populations, and it is uncertain whether virtual RCTs (vRCTs) enhance representativeness or if elements of their consent and enrollment processes may instead contribute to underrepresentation of these groups. In this study, we aimed to identify disparities in enrollment demographics in a vRCT, the BE ACTIVE study, which recruited patients within a single health system. We discovered that the proportions of eligible patients who were randomized differed significantly by gender and race/ethnicity (men 1.2%, women 2.0%, P < .001; White 1.8%, Black 1.3%, Hispanic 0.7%, Asian 0.9%; P < .001), and compared with White patients, non-White patients were less likely to have a valid email address on file and were less likely to click on the email link to the study webpage and begin enrollment., Competing Interests: Conflict of Interest Dr. Volpp is a co-owner of a behavioral economics consulting firm, VAL Health. All other authors report no relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Physical activity is associated with a lower risk of major adverse cardiovascular events, but few individuals achieve guideline-recommended levels of physical activity. Strategies informed by behavioral economics increase physical activity, but their longer-term effectiveness is uncertain. We sought to determine the effect of behaviorally designed gamification, loss-framed financial incentives, or their combination on physical activity compared with attention control over 12-month intervention and 6-month postintervention follow-up periods., Methods: Between May 2019 and January 2024, participants with clinical atherosclerotic cardiovascular disease or a 10-year risk of myocardial infarction, stroke, or cardiovascular death of ≥7.5% by the Pooled Cohort equation were enrolled in a pragmatic randomized clinical trial. Participants received a wearable device to track daily steps, established a baseline, selected a step goal increase, and were randomly assigned to control (n=151), behaviorally designed gamification (n=304), loss-framed financial incentives (n=302), or gamification+financial incentives (n=305). The primary outcome of the trial was the change in mean daily steps from baseline through the 12-month intervention period., Results: A total of 1062 patients (mean±SD age, 67±8; 61% female; 31% non-White) were enrolled. Compared with control subjects, participants had significantly greater increases in mean daily steps from baseline during the 12-month intervention in the gamification arm (adjusted difference, 538.0 [95% CI, 186.2-889.9]; P =0.0027), financial incentives arm (adjusted difference, 491.8 [95% CI, 139.6-844.1]; P =0.0062), and gamification+financial incentives arm (adjusted difference, 868.0 [95% CI, 516.3-1219.7]; P <0.0001). During the 6-month follow-up, physical activity remained significantly greater in the gamification+financial incentives arm than in the control arm (adjusted difference, 576.2 [95% CI, 198.5-954]; P =0.0028), but it was not significantly greater in the gamification (adjusted difference, 459.8 [95% CI, 82.0-837.6]; P =0.0171) or financial incentives (adjusted difference, 327.9 [95% CI, -50.2 to 706]; P =0.09) arms after adjustment for multiple comparisons., Conclusions: Behaviorally designed gamification, loss-framed financial incentives, and the combination of both increased physical activity compared with control over a 12-month intervention period, with the largest effect in gamification+financial incentives. These interventions could be a useful component of strategies to reduce cardiovascular risk in high-risk patients., Registration: URL: https://clinicaltrials.gov; Unique Identifier: NCT03911141., Competing Interests: Disclosures Dr Volpp is a co-owner of a behavioral economics consulting firm, VAL Health. All other authors report no conflicts.

Background: The extent and consequences of ischemia in patients with chronic limb-threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis-to-limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI., Methods and Results: In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk-adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time <30 days, there was no association between D2L time and all-cause death or major lower extremity amputation. However, among patients with D2L time >30 days, each additional 10-day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014-1.036]). There was no association between D2L time and all-cause death., Conclusions: A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.

Antiplatelet therapy is the cornerstone of the secondary prevention of cardiovascular disease. Aspirin is indicated for all patients with chronic coronary disease to prevent recurrent ischemic events. A more potent antithrombotic therapy-including P2Y12 inhibitor monotherapy, dual antiplatelet therapy, or vascular dose anticoagulation-reduces the risk of ischemic events but also increases bleeding risk. Clinicians must weigh both ischemic risks and bleeding risks when determining an optimal antithrombotic therapy for patients with chronic coronary disease, and soliciting patient involvement in shared decision-making is critical., Competing Interests: Disclosure The authors report no disclosures relevant to the content of this manuscript., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Supervised exercise therapy improves walking performance, functional capacity, and quality of life in patients with peripheral artery disease (PAD). However, few patients with PAD are enrolled in supervised exercise programs, and there are a number of logistical and financial barriers to their participation. A home-based walking intervention is likely to be more accessible to patients with PAD, but no fully home-based walking program has demonstrated efficacy. Concepts from behavioral economics have been used to design scalable interventions that increase daily physical activity in patients with atherosclerotic vascular disease, but whether a similar program would be effective in patients with PAD is uncertain., Study Design and Objectives: GAMEPAD (NCT04536012) is a pragmatic, virtual, randomized controlled trial designed to evaluate the effectiveness of a gamification strategy informed by concepts from behavioral economics to increase daily physical activity in patients with PAD who are seen in cardiology and vascular surgery clinics affiliated with the University of Pennsylvania Health System. Patients are contacted by email or text message, and complete enrollment and informed consent on the Penn Way to Health online platform. A GAMEPAD substudy will evaluate the effectiveness of opt-in versus opt-out framing when approaching patients for study participation. Patients are then provided with a wearable fitness tracker, establish a baseline daily step count, set a goal to increase daily step count by 33%-50%, and are randomized 1:1 to the gamification or control arms. Interventions continue for 16 weeks, including a 4-week period during which goal step count is gradually increased in the gamification arm, with follow-up for an additional 8 weeks to evaluate the durability of behavior change. The trial has met its enrollment goal of 102 participants, with a primary endpoint of change from baseline in daily steps over the 16-week intervention period. Key secondary endpoints include change from baseline in daily steps over the 8-week postintervention follow-up period and changes in patient-reported measures of PAD symptoms and quality of life over the intervention and follow-up periods., Conclusions: GAMEPAD is a virtual, pragmatic randomized clinical trial of a novel, fully home-based walking intervention informed by concepts from behavioral economics to increase physical activity and PAD-specific quality of life in patients with PAD. Its results will have important implications for the application of behavioral economic concepts to scalable home-based strategies to promote physical activity in patients with PAD and other disease processes where physical activity is limited by exertional symptoms., Clinical Trial Registration: clinicaltrials.gov; NCT04536012., Competing Interests: Conflict of Interest Dr. Fanaroff reports research funding to the institution from Abbott. Dr. Damrauer reports research funding to the institution from RenalytixAI and in-kind research support from Novo Nordisk. Dr. Patel reported receiving personal fees as the owner of Catalyst Health LLC. All other authors report no relevant conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Racial residential segregation is associated with racial health inequities, but it is unclear if segregation may exacerbate Black-White disparities in cardiovascular disease (CVD) mortality. This study aimed to assess associations between Black-White residential segregation, CVD mortality rates among non-Hispanic (NH) Black and NH White populations, and Black-White disparities in CVD mortality., Methods: This cross-sectional study analyzed Black-White residential segregation, as measured by county-level interaction index, of US counties, county-level CVD mortality among NH White and NH black adults aged 25 years and older, and county-level Black-White disparities in CVD mortality in years 2014 to 2017. Age-adjusted, county-level NH Black CVD mortality rates and NH White cardiovascular disease mortality rates, as well as group-level relative risk ratios for Black-White cardiovascular disease mortality, were calculated. Sequential generalized linear models adjusted for county-level socioeconomic and neighborhood factors were used to estimate associations between residential segregation and cardiovascular mortality rates among NH Black and NH White populations. Relative risk ratio tests were used to compare Black-White disparities in the most segregated counties to disparities in the least segregated counties., Results: We included 1,286 counties with ≥5% Black populations in the main analysis. Among adults aged ≥25 years, there were 2,611,560 and 408,429 CVD deaths among NH White and NH Black individuals, respectively. In the unadjusted model, counties in the highest tertile of segregation had 9% higher (95% CI, 1%-20% higher, P = .04) rates of NH Black CVD mortality than counties in the lowest tertile of segregation. In the multivariable adjusted model, the most segregated counties had 15% higher (95% CI, 0.5% to 38% higher, P = .04) rates of NH Black CVD mortality than the least segregated counties. In the most segregated counties, NH Black individuals were 33% more likely to die of CVD than NH White individuals (RR 1.33, 95% CI 1.32 to 1.33, P < .001)., Conclusions: Counties with increased Black-White residential segregation have higher rates of NH Black CVD mortality and larger Black-White disparities in CVD mortality. Identifying the causal mechanisms through which racial residential segregation widens disparities in CVD mortality requires further study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: Inadequate representation of older patients, women, and racial minority individuals in cardiovascular clinical trials limits both the generalizability of trial findings and inclusivity in access to novel therapies and therapeutic strategies., Objective: To report on temporal trends in the representation of older patients, women, and racial and ethnic minority individuals in clinical trials studying treatments for valvular heart disease., Evidence Review: All published clinical trials enrolling more than 100 adults with any valvular heart disease published between 2005 and 2020 were included after searches with PubMed and ClinicalTrials.gov. Data on age, sex, race, and ethnicity reported in the included studies were collected. Trials were assigned to 4 time periods based on the publication date, and temporal trends were analyzed in the representation of older patients, women, and racial and ethnic minority individuals., Findings: A total of 139 clinical trials with 51 527 participants were identified. Of these trials, 103 (74%) investigated aortic valve disease and the remainder mitral valve disease. Overall, 63 trials (45.3%) enrolled patients only in Europe, 24 (17.3%) only in North America, and 19 (13.7%) in multiple geographical regions. The weighted mean (SD) age of enrolled patients was 68.4 (11.4) years, increasing nonsignificantly from 61.9 (5.9) years in 2005-2008 to 72.8 (9.6) years in 2017-2020 (P = .09 for trend). The overall proportion of women enrolled in valvular heart disease trials was 41.1%, with no significant changes over time. Data on race and ethnicity of trial participants were reported in 13 trials (9.4%), in which trial-level representation of American Indian/Alaska Native, Asian, Black/African American, Hispanic, and Native Hawaiian/Pacific Islander patients ranged from 0.27% to 43.9%. There were no significant temporal trends noted in the enrollment of racial and ethnic minority populations. The representation of women in clinical trials was positively associated with enrollment rates of older patients and underrepresented racial and ethnic groups., Conclusions and Relevance: This review found that over the past 2 decades, women and racial and ethnic minority individuals have remained underrepresented in North American valvular heart disease clinical trials. Further work is needed to improve the reporting of race and ethnicity data and address barriers to trial enrollment for older patients, women, and racial and ethnic minority individuals.

Background: We assess the rates of device use and outcomes by race among patients undergoing lower extremity peripheral arterial intervention using the American College of Cardiology National Cardiovascular Data Registry-Peripheral Vascular Intervention (PVI) registry., Methods: Patients who underwent PVI between April 2014 and March 2019 were included. Socioeconomic status was evaluated using the Distressed Community Index score for patients' zip codes. Multivariable logistic regression was used to assess factors associated with utilization of drug-eluting technologies, intravascular imaging, and atherectomy. Among patients with Centers for Medicare and Medicaid Services data, we compared 1-year mortality, rates of amputation, and repeat revascularizations., Results: Of 63 150 study cases, 55 719 (88.2%) were performed in White patients and 7431 (11.8%) in Black patients. Black patients were younger (67.9 versus 70.0 years), had higher rates of hypertension (94.4% versus 89.5%), diabetes (63.0% versus 46.2%), less likely to be able to walk 200 m (29.1% versus 24.8%), and higher Distressed Community Index scores (65.1 versus 50.6). Black patients were provided drug-eluting technologies at a higher rate (adjusted odds ratio, 1.14 [95% CI, 1.06-1.23]) with no difference in atherectomy (adjusted odds ratio, 0.98 [95% CI, 0.91-1.05]) or intravascular imaging (adjusted odds ratio, 1.03 [95% CI, 0.88-1.22]) use. Black patients experienced a lower rate of acute kidney injury (adjusted odds ratio, 0.79 [95% CI, 0.72-0.88]). In Centers for Medicare and Medicaid Services-linked analyses of 7429 cases (11.8%), Black patients were significantly less likely to have surgical (adjusted hazard ratio, 0.40 [95% CI, 0.17-0.96]) or repeat PVI revascularization (adjusted hazard ratio, 0.42 [95% CI, 0.30-0.59]) at 1 year compared with White patients. There was no difference in mortality (adjusted hazard ratio [0.8-1.4]) or major amputation (adjusted hazard ratio, 2.5 [95% CI, 0.8-7.6]) between Black and White patients., Conclusions: Black patients presenting for PVI were younger, had higher prevalence of comorbidities and lower socioeconomic status. After adjustment, Black patients were less likely to have surgical or repeat PVI revascularization after the index PVI procedure., Competing Interests: Disclosures Dr Julien discloses equity in Johnson and Johnson and Shockwave Medical stock. Dr Curtis has an institutional contract with the American College of Cardiology for his role as Senior Scientific Advisor of the National Cardiovascular Data Registry; has received salary support from the American College of Cardiology and Centers for Medicaid & Medicare Services; and has equity in Medtronic. Dr Fanaroff has reports a career development award from the American Heart Association, research funding to his institution from Boston Scientific, and consulting fees from the American Heart Association. Dr Khatana has received grant support from under National Heart, Lung, and Blood Institute (5K23 HL153772-02) and the American Heart Association (20CDA35320251). Dr Secemsky has Research grants to Beth Israel Deaconess Medical Center: NIH/National Heart Lung and Blood Institute K23HL150290, Harvard Medical School’s Shore Faculty Development Award, AstraZeneca, Becton Dickinson, Boston Scientific, Cook, CSI, Laminate Medical, Medtronic and Philips. Consulting/Speaking: Abbott, Asahi, Bayer, BD, Boston Scientific, Cook, Cardiovascular Systems Incorporated, Inari, Janssen, Medtronic, Philips, and VentureMed. Dr Vora has received education and research funding from Medtronic. Dr Armstrong has consulted for Abbott Vascular, Boston Scientific, Cardiovascular Systems, Medtronic, and Spectranetics. Dr Jaff is employed on a part time basis by Boston Scientific and shareholder of Boston Scientific Corporation. Dr Giri has served on advisory boards for Astra Zeneca, Philips Medical, Boston Scientific and Inari Medical, and received research funds to the institution from St. Jude Medical, Boston Scientific, Inari Medical, and Recor Medical. The other authors report no conflicts.

Background: Higher levels of physical activity are associated with improvements in cardiovascular health, and consensus guidelines recommend that individuals with or at risk for atherosclerotic cardiovascular disease (ASCVD) participate in regular physical activity. However, most adults do not achieve recommended levels of physical activity. Concepts from behavioral economics have been used to design scalable interventions that increase physical activity over short time periods, but the longer-term efficacy of these strategies is uncertain., Study Design and Objectives: BE ACTIVE (NCT03911141) is a pragmatic, virtual, randomized controlled trial designed to evaluate the effectiveness of 3 strategies informed by behavioral economic concepts to increase daily physical activity in patients with established ASCVD or 10-year ASCVD risk > 7.5% who are seen in primary care and cardiology clinics affiliated with the University of Pennsylvania Health System. Patients are contacted by email or text message, and complete enrollment and informed consent on the Penn Way to Health online platform. Patients are then provided with a wearable fitness tracker, establish a baseline daily step count, set a goal to increase daily step count by 33% to 50%, and are randomized 1:2:2:2 to control, gamification, financial incentives, or both gamification and financial incentives. Interventions continue for 12 months, with follow-up for an additional 6 months to evaluate the durability of behavior change. The trial has met its enrollment goal of 1050 participants, with a primary endpoint of change from baseline in daily steps over the 12-month intervention period. Key secondary endpoints include change from baseline in daily steps over the 6-month post-intervention follow-up period and change in moderate to vigorous physical activity over the intervention and follow-up periods. If the interventions prove effective, their effects on life expectancy will be compared with their costs in cost-effectiveness analysis., Conclusions: BE ACTIVE is a virtual, pragmatic randomized clinical trial powered to demonstrate whether gamification, financial incentives, or both are superior to attention control in increasing physical activity. Its results will have important implications for strategies to promote physical activity in patients with or at risk for ASCVD, as well as for the design and implementation of pragmatic virtual clinical trials within health systems., Competing Interests: Conflict of interest Dr. Fanaroff reports a career development grant from the American Heart Association. Dr. Patel is an employee of Ascension Health. Dr. Volpp is a co-owner of a behavioral economics consulting firm, VAL Health. All other authors report no relevant conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Chronic limb-threatening ischemia (CLTI) is a common condition with high rates of morbidity and mortality. Despite extensive literature documenting poor outcomes in patients with CLTI, as well as racial, ethnic, socioeconomic, and geographic disparities in these outcomes, process measures for high-quality CLTI care have not been developed. We developed the Chronic Limb threatening Ischemia Process PERformace (CLIPPER) cohort to develop and test the validity of CLTI care quality measures., Methods: Using inpatient and outpatient claims data from patients with fee-for-service Medicare from 2010 to 2019, we created a coding algorithm to identify patients with CLTI. To qualify for a CLTI diagnosis, patients had to have either diagnostic codes for peripheral artery disease and for ulceration, infection, or gangrene on the same inpatient or outpatient claim or a CLTI-specific diagnostic code. Patients were also required to have a procedural code indicating arterial vascular testing within 6 months before or after the earliest qualifying CLTI diagnostic code(s). We describe baseline characteristics and long-term outcomes of this cohort., Results: The final cohort comprised 1,130,065 patients diagnosed with CLTI between 2010 and 2019. Mean (±SD) age of the cohort was 75 ± 5.8 years; 48.4% were women, and 14.6% were Black. Within 30 days of CLTI diagnosis, 20.4% of patients underwent either percutaneous or surgical revascularization. Within 6 months, 3.3% of patients underwent major amputation; 16.7% of patients died within 1 year and 50.3% within 5 years., Conclusions: We described the development of a cohort of fee-for-service Medicare patients with CLTI using inpatient and outpatient Medicare claims data. CLIPPER will be a resource for developing a set of process measures that can be captured from administrative claims data, with plans to describe their association with limb outcomes and corresponding racial, ethnic, socioeconomic, sex-based, and geographic variability., (© 2023 The Author(s).)

Background: Obesity is strongly associated with cardiovascular disease, particularly through its effects on blood pressure. Though maintaining a negative caloric balance leads to weight loss, many patients struggle to adhere to low calorie diets over the long term. Time-restricted eating, a subtype of intermittent fasting (IF), may be an easier dietary pattern for patients to initiate and maintain. We tested the feasibility of a bidirectional texting strategy to help patients with obesity and hypertension initiate and maintain time-restricted eating, and whether a commitment device, a pledge to behave in a certain way in the future while making nonadherence costlier, would increase adherence beyond bidirectional texting., Methods: Patients with obesity and hypertension seen in cardiology clinics were provided education on time-restricted eating and randomized to a commitment device versus attention control. Attention control consisted of daily bidirectional text messages asking whether patients adhered to IF and weekly text messages asking participants to send their weight and blood pressure. The commitment device involved the same text messages as attention control, plus a commitment contract, setting of implementation intentions with respect to details of time-restricted eating, and involvement of a support partner who received weekly updates on the participant's adherence to time-restricted eating. The intervention lasted 12 weeks, followed by a 6-week follow-up period. The primary outcome was days per week adherent to time-restricted eating over the 18-week study period, measured by daily self-report. We also compared change from baseline weight and blood pressure between randomized groups., Results: A total of 37 patients were randomized and started the study-20 to attention control and 17 to the commitment device. Mean age was 60 years old, and mean BMI was 38.4 kg/m 2 . Over the 18-week study period, the mean ± standard deviation (SD) number of days per week adherent to time-restricted eating was 4.7 ± 1.9 in the control arm and 5.4 ± 1.7 in the intervention arm (P = .23). Mean systolic blood pressure declined from 135 to 128 mm Hg among all participants (P = .006) with no difference between groups in change from baseline blood pressure (P = .74). Weight decreased from 229 to 223 pounds among all participants (P = .25) with no significant difference between groups in change from baseline weight (P = .84)., Conclusions: A bidirectional texting strategy was feasible for helping patients with obesity and hypertension initiate and adhere to time-restricted eating. Adding a commitment device to bidirectional texting did not increase adherence to time-restricted eating compared with attention control, nor were there significant between group changes in blood pressure or weight, but these comparisons were underpowered. A larger randomized trial of the effect of this scalable intervention, compared with usual care, on blood pressure and weight among patients with obesity and hypertension is warranted., Clinical Trials Registration: clinicaltrials.gov; unique identifier: NCT04836312., Competing Interests: Disclosures Dr Fanaroff reports research grants from the American Heart Association and National Institutes of Health. Dr Adusumalli reports full-time employment by CVS Health Corporation. Dr Chokshi reports research grants from Independence Blue Cross and National Institutes of Health. Dr Patel reports full-time employment by Ascension Health. All other authors report no relevant disclosures., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background Inequitable access to high-technology therapeutics may perpetuate inequities in care. We examined the characteristics of US hospitals that did and did not establish left atrial appendage occlusion (LAAO) programs, the patient populations those hospitals served, and the associations between zip code-level racial, ethnic, and socioeconomic composition and rates of LAAO among Medicare beneficiaries living within large metropolitan areas with LAAO programs. Methods and Results We conducted cross-sectional analyses of Medicare fee-for-service claims for beneficiaries aged 66 years or older between 2016 and 2019. We identified hospitals establishing LAAO programs during the study period. We used generalized linear mixed models to measure the association between zip code-level racial, ethnic, and socioeconomic composition and age-adjusted rates of LAAO in the most populous 25 metropolitan areas with LAAO sites. During the study period, 507 candidate hospitals started LAAO programs, and 745 candidate hospitals did not. Most new LAAO programs opened in metropolitan areas (97.4%). Compared with non-LAAO centers, LAAO centers treated patients with higher median household incomes (difference of $913 [95% CI, $197-$1629], P =0.01). Zip code-level rates of LAAO procedures per 100 000 Medicare beneficiaries in large metropolitan areas were 0.34% (95% CI, 0.33%-0.35%) lower for each $1000 zip code-level decrease in median household income. After adjustment for socioeconomic markers, age, and clinical comorbidities, LAAO rates were lower in zip codes with higher proportions of Black or Hispanic patients. Conclusions Growth in LAAO programs in the United States had been concentrated in metropolitan areas. LAAO centers treated wealthier patient populations in hospitals without LAAO programs. Within major metropolitan areas with LAAO programs, zip codes with higher proportions of Black and Hispanic patients and more patients experiencing socioeconomic disadvantage had lower age-adjusted rates of LAAO. Thus, geographic proximity alone may not ensure equitable access to LAAO. Unequal access to LAAO may reflect disparities in referral patterns, rates of diagnosis, and preferences for using novel therapies experienced by racial and ethnic minority groups and patients experiencing socioeconomic disadvantage.

Importance: Racial and ethnic minority and socioeconomically disadvantaged patients have been underrepresented in randomized clinical trials. Efforts have focused on enhancing inclusion of minority groups at sites participating at clinical trials; however, there may be differences in the patient populations of the sites that participate in clinical trials., Objective: To identify any differences in the racial, ethnic, and socioeconomic composition of patient populations among candidate sites in the US that did vs did not participate in trials for novel transcatheter therapies., Design, Setting, and Participants: This cross-sectional analysis used Medicare Provider Claims from 2019 for patients admitted to hospitals in the US. All clinical trials for transcatheter mitral and tricuspid valve therapies and the hospitals participating in each of the trials were identified using ClinicalTrials.gov. Hospitals with active cardiac surgical programs that did not participate in the trials were also identified. Data analysis was performed between July 2021 and July 2022., Exposures: Multivariable linear regression models were used to identify differences in racial, ethnic, and socioeconomic characteristics among patients undergoing cardiac surgery or transcatheter aortic valve replacement at trial vs nontrial hospitals., Main Outcome and Measures: The main outcome of the study was participation in a clinical trial for novel transcatheter mitral or tricuspid valve therapies., Results: A total of 1050 hospitals with cardiac surgery programs were identified, of which 121 (11.5%) participated in trials for transcatheter mitral or tricuspid therapies. Patients treated in trial hospitals had a higher median zip code-based household income (difference of $5261; 95% CI, $2986-$7537), a lower Distressed Communities Index score (difference of 5.37; 95% CI, 2.59-8.15), and no significant difference in the proportion of patients dual eligible for Medicaid (difference of 0.86; 95% CI, -2.38 to 0.66). After adjusting for each of the socioeconomic indicators separately, there was less than 1% difference in the proportion of Black and Hispanic patients cared for at hospitals participating vs not participating in clinical trials., Conclusions and Relevance: In this cohort study among candidate hospitals for clinical trials for transcatheter mitral or tricuspid valve therapies, trial hospitals took care of a more socioeconomically advantaged population than nontrial hospitals, with a similar proportion of Black and Hispanic patients. These data suggest that site selection efforts may improve enrollment of socioeconomically disadvantaged patients but may not improve the enrollment of Black and Hispanic patients.

Shortly after the emergence of coronavirus disease 2019 (COVID-19) in late 2019, clinicians rapidly recognized an apparent association between the disease and both arterial and venous thrombotic complications, which was confirmed in epidemiologic studies. Based on these data, hospitals empirically developed and implemented protocols with different strategies for anticoagulation of hospitalized COVID-19 patients. Subsequent randomized controlled trials (RCTs) clarified the role of anticoagulation in patients hospitalized with COVID-19 and recently discharged from the hospital. In this review, we discuss the epidemiology and pathophysiology of thrombosis in patients with COVID-19, observational comparative effectiveness analyses that provided hints of a benefit from anticoagulation, and finally the RCTs that established which patients with COVID-19 benefit from treatment-dose anticoagulation. These RCTs have demonstrated that hospitalized, noncritically ill patients with COVID-19 benefit from treatment-dose anticoagulation, but patients who are hospitalized and critically ill, discharged from the hospital, or not hospitalized do not benefit.

Background: Randomized clinical trials are the gold standard to assess the causal relationship between an intervention and subsequent outcomes, also known as clinical endpoints. In order to limit bias, central clinical events committees (CEC) are established to ensure consistent event reporting across participating centers, as well as complete and accurate ascertainment of endpoints. However, defining independence is challenging., Methods: This consensus statement was generated by teleconferences and electronic communications among clinical research organizations from the United States, Europe and Australia. This document does not constitute regulatory guidance., Results: An independent CEC is defined when the adjudicators are not primarily involved in designing, funding, sponsoring, organizing, conducting, analyzing or regulating the clinical trial for which they serve as an adjudicator, beyond their role as CEC member. Moreover, independence requires absence of conflicts of interest with the steering committee, sponsor, grant giver, manufacturer, coordinating center, other independent committees, core laboratories, medical monitor, safety physician, participating clinical sites, statistician or data manager, regulatory agencies or authorities, which could influence (or be perceived to influence) a member's objectivity in evaluating trial data. Such conflicts of interest include financial benefits, directing or advisory role (paid or unpaid), decision-making position, as well as being a direct relative. An independent adjudicator has no other role within a clinical trial., Conclusions: This consensus statement presents a standardized definition of an independent CEC to be considered by clinical research organizations, manufacturers, and investigators. In addition, it provides recommendations on best practices for implementation of an independent CEC., (Copyright © 2022. Published by Elsevier Inc.)

Competing Interests: Competing interests: We have read and understood BMJ policy on declaration of interests and have no relevant interests to declare.

Background: Novel P2Y12 inhibitors prasugrel and ticagrelor were approved for patients with acute coronary syndrome (ACS) in 2009 and 2011, respectively. We assessed the association of racial, ethnic, and socioeconomic factors with initiation of and adherence to novel P2Y12 inhibitors in a commercially insured population., Methods: We performed a retrospective cohort analysis of adults undergoing percutaneous coronary intervention with placement of a drug-eluting stent, stratified by ACS status, between January 2008 and December 2016 using Clinformatics Data Mart (OptumInsight). We estimated multivariable logistic regression models to identify factors associated with the initiation of clopidogrel vs novel P2Y12 inhibitors as well as subsequent 6-month medication adherence, assessed via pharmacy records., Results: A total of 55,664 patients were included in the analysis. Hispanic ethnicity was independently associated with the initiation of clopidogrel compared with novel P2Y12 inhibitors among ACS patients (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.04-1.36; P<.01). ACS patients with an annual median household income of over $100,000 were less likely to be started on clopidogrel when compared with those who earned less than $40,000 (OR, 0.67; 95% CI, 0.61-0.75; P<.01). Black race, Hispanic ethnicity, and lower household income were each associated with significantly reduced odds of P2Y12 inhibitor adherence., Conclusion: Hispanic ethnicity and lower household income were associated with novel P2Y12 inhibitor initiation, and non-White race and ethnicity were associated with lower P2Y12 inhibitor adherence over 6-month follow-up. These findings highlight continued inequity of care, even in an insured population, and point to a need for new strategies to close these gaps.

The non-vitamin K antagonist oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, and edoxaban have transformed the management of atrial fibrillation (AF), but are only approved by regulatory authorities for stroke prophylaxis in patients with so-called "non-valvular AF." This terminology has spawned confusion about which patients with valvular heart disease benefit from NOACs and which should be treated with vitamin K antagonists (VKAs) instead. Patients with valvular heart disease other than mechanical prosthetic valves or severe mitral stenosis (including those with bioprosthetic valves) were included in pivotal trials demonstrating the benefit of NOACs over VKAs, and consensus guidelines recommend NOACs over VKAs in these patients. Subsequent devoted randomized controlled trials in patients with AF and bioprosthetic valves, including transcatheter valves, have confirmed the safety of NOACs in this population. In patients with rheumatic mitral stenosis, observational studies indicate that NOACs may be safe and effective, but randomized controlled trials are ongoing. By contrast, a randomized controlled trial showed that dabigatran is harmful in patients with mechanical prosthetic mitral valves; however, these data may not extrapolate to patients with mechanical valve prostheses in other locations or to other NOACs, and randomized controlled trials are ongoing. In this review, we discuss these data in greater depth, and make recommendations for the use of NOACs in patients with valvular heart disease., (Published on behalf of the European Society of Cardiology. © The Author(s) 2022.)

Background: The use of apixaban instead of vitamin K antagonists (VKA) as well as dropping aspirin results in less bleeding and comparable ischemic events in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention treated with a P2Y 12 inhibitor., Objectives: The authors assessed the safety and efficacy of antithrombotic regimens according to HAS-BLED and CHA 2 DS 2 -VASc scores in AUGUSTUS (The Open-Label, 2 × 2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention)., Methods: In AUGUSTUS, 4,614 patients were randomized in a 2-by-2 factorial design to open-label apixaban or VKA and blinded aspirin or placebo. The primary endpoint was major or clinically relevant nonmajor bleeding over 6 months of follow-up. Cox proportional hazards models were used to assess treatment effects by baseline HAS-BLED (≤2 vs ≥3) and CHA 2 DS 2 -VASc (≤2 vs ≥3) scores., Results: Of 4,386 (95.1%) patients with calculable scores, 66.8% had HAS-BLED ≥3 and 81.7% had CHA 2 DS 2 -VASc ≥3. Bleeding rates were lower with apixaban than VKA irrespective of baseline risk (HR: 0.57; 95% CI: 0.41-0.78 [HAS-BLED ≤2]; HR: 0.72; 95% CI: 0.59-0.88 [HAS-BLED ≥3]; interaction P = 0.23). Aspirin increased bleeding irrespective of baseline risk (HR: 1.86; 95% CI: 1.36-2.56 [HAS-BLED ≤2]; HR: 1.81; 95% CI: 1.47-2.23 [HAS-BLED ≥3]; interaction P = 0.88). Apixaban resulted in a lower risk of death or hospitalization than VKA without a significant interaction with baseline stroke risk (HR: 0.92; 95% CI: 0.67-1.25 [CHA 2 DS 2 -VASc ≤2]; HR: 0.82; 95% CI: 0.73-0.94 [CHA 2 DS 2 -VASc ≥3]; interaction P = 0.53)., Conclusions: Our findings support the use of apixaban and a P2Y 12 inhibitor without aspirin for most patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention, irrespective of a patient's baseline bleeding and stroke risk (NCT02415400)., Competing Interests: Funding Support and Author Disclosures The AUGUSTUS trial and this analysis were supported by Bristol Myers Squibb and Pfizer. Dr Fanaroff has received research grants and consulting fees from the American Heart Association; and has received research grants from Boston Scientific. Dr Lopes has received institutional research grants and consulting fees from Bristol Myers Squibb, Pfizer, GlaxoSmithKline, Medtronic PLC, and Sanofi; and has received consulting fees from Amgen, Bayer, and Boehringer Ingelheim. Dr Goodman has received research grant support (eg, steering committee or data and safety monitoring committee) and/or speaker/consulting honoraria (eg, advisory boards) from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, GlaxoSmithKline, HLS Therapeutics, JAMP Pharma, Janssen/Johnson and Johnson, Merck, Novartis, Novo Nordisk A/C, Pendopharm, Pfizer, Regeneron, Sanofi, Servier, and Valeo Pharma; and has received salary support/honoraria from the Heart and Stroke Foundation of Ontario/University of Toronto (Polo) (Chair), Canadian Heart Research Centre and MD Primer, Canadian VIGOUR Centre, Cleveland Clinic Coordinating Centre for Clinical Research, Duke Clinical Research Institute, New York University Clinical Coordinating Centre, and PERFUSE Research Institute. Dr Thomas has received institutional research grants from Akili Interactive Labs Inc, Amgen Inc, Gilead, and Novartis. Dr Aronson is an employee of Bristol Myers Squibb. Dr Windecker has received Institutional research and educational grants from Abbott, Amgen, Bayer, Bristol Myers Squibb, CSL Behring, Boston Scientific, Biotronik, Edwards Lifesciences, Medtronic, Polares, and Sinomed. Dr Mehran has received institutional research grants from AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb/Sanofi, CSL Behring, Eli Lilly/Daiichi-Sankyo, Medtronic, Novartis, and OrbusNeich; has received consulting fees from Boston Scientific, Abbott Vascular, Medscape, Siemens Medical Solutions, Roivant Sciences Inc, and Sanofi; has performed consulting (no fees) for Regeneron Pharmaceuticals; has received institutional consulting fees from Abbott Vascular, Spectranetics/Phillips/Volcano Corporation, Bristol Myers Squibb, Novartis, and Watermark Research; has served as an executive committee member for Janssen Pharmaceuticals and Bristol Myers Squibb; and has <1% equity in Claret Medical and Elixir Medical. Dr Granger has received research grants from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Armetheon, AstraZeneca, the U.S. Food and Drug Administration, GlaxoSmithKline, The Medicines Company, Medtronic Foundation, Medtronic Inc, and Novartis; and has received consulting fees from Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Daiichi-Sankyo, Janssen, Pfizer, Abbvie, Armetheon, AstraZeneca, Eli Lilly, Gilead, GlaxoSmithKline, Hoffmann-La Roche, The Medicines Company, National Institutes of Health, Novartis, Sirtex, Verseon, Apple, Medscape, LLC, Merck, Novo Nordisk, Roche Diagnostics, and Rho Pharmaceuticals. Dr Alexander has received institutional research grants and consulting fees/honoraria from Bristol Myers Squibb and CSL Behring; has received institutional research grants from AstraZeneca, CryoLife, the U.S. Food and Drug Administration, National Institutes of Health, Sanofi, VoluMetrix, and Boehringer Ingelheim; and has received consulting fees/honoraria from Pfizer, AbbVie Pharmaceuticals, NovoNordisk, Portola Pharmaceuticals, Quantum Genetics, Teikoku Pharmaceuticals, VA Cooperative Studies Program, and Zafgen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of aortic stenosis, with the number of procedures and sites offering the procedure steadily rising over the past decade in the United States. Despite this, growth into certain markets has been limited as hospitals have to balance high TAVR costs with the ability to offer a complete array of state-of-the-art therapies for aortic stenosis. This trade-off often results in decreased access to TAVR services by patients cared for in hospitals that cannot afford these services or have difficulty meeting procedural requirements, recruiting skilled physicians, and initiating and then maintaining a functioning TAVR program. The lack of access is more common among patients of color or those who are socioeconomically disadvantaged. The purpose of this review is to describe the hospital-level economic considerations of TAVR in the United States and the resulting effects on geographic, racial, ethnic, and socioeconomic access for Americans.

Importance: Despite the benefits of high-technology therapeutics, inequitable access to these technologies may generate disparities in care., Objective: To examine the association between zip code-level racial, ethnic, and socioeconomic composition and rates of transcatheter aortic valve replacement (TAVR) among Medicare patients living within large metropolitan areas with TAVR programs., Design, Setting, and Participants: This multicenter, nationwide cross-sectional analysis of Medicare claims data between January 1, 2012, and December 31, 2018, included beneficiaries of fee-for-service Medicare who were 66 years or older living in the 25 largest metropolitan core-based statistical areas., Exposure: Receipt of TAVR., Main Outcomes and Measures: The association between zip code-level racial, ethnic, and socioeconomic composition and rates of TAVR per 100 000 Medicare beneficiaries., Results: Within the studied metropolitan areas, there were 7590 individual zip codes. The mean (SD) age of Medicare beneficiaries within these areas was 71.4 (2.0) years, a mean (SD) of 47.6% (5.8%) of beneficiaries were men, and a mean (SD) of 4.0% (7.0%) were Asian, 11.1% (18.9%) were Black, 8.0% (12.9%) were Hispanic, and 73.8% (24.9%) were White. The mean number of TAVRs per 100 000 Medicare beneficiaries by zip code was 249 (IQR, 0-429). For each $1000 decrease in median household income, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.2% (95% CI, 0.1%-0.4%) lower (P = .002). For each 1% increase in the proportion of patients who were dually eligible for Medicaid services, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 2.1% (95% CI, 1.3%-2.9%) lower (P < .001). For each 1-unit increase in the Distressed Communities Index score, the number of TAVR procedures performed per 100 000 Medicare beneficiaries was 0.4% (95% CI, 0.2%-0.5%) lower (P < .001). Rates of TAVR were lower in zip codes with higher proportions of patients of Black race and Hispanic ethnicity, despite adjusting for socioeconomic markers, age, and clinical comorbidities., Conclusions and Relevance: Within major metropolitan areas in the US with TAVR programs, zip codes with higher proportions of Black and Hispanic patients and those with greater socioeconomic disadvantages had lower rates of TAVR, adjusting for age and clinical comorbidities. Whether this reflects a different burden of symptomatic aortic stenosis by race and socioeconomic status or disparities in use of TAVR requires further study.

Importance: Randomized clinical trials have shown that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause significant weight loss and reduce cardiovascular events in patients with type 2 diabetes (T2D). Black patients have a disproportionate burden of obesity and cardiovascular disease and have a higher rate of cardiovascular-related mortality. Racial and ethnic disparities in health outcomes are largely attributable to the pervasiveness of structural racism, and patients who are marginalized by racism have less access to novel therapeutics., Objectives: To evaluate GLP-1 RA uptake among a commercially insured population of patients with T2D; identify associations of race, ethnicity, sex, and socioeconomic status with GLP-1 RA use; and specifically examine its use among the subgroup of patients with atherosclerotic cardiovascular disease (ASCVD) because of the known benefit of GLP-1 RA use for this population., Design Setting and Participants: This was a retrospective cohort analysis using data from OptumInsight Clinformatics Data Mart of commercially insured adult patients with T2D (with or without ASCVD) in the US. Data from October 1, 2015, to June 31, 2019, were included, and the analyses were performed in July 2020. We estimated multivariable logistic regression models to identify the association of race, ethnicity, sex, and socioeconomic status with GLP-1 RA use., Main Outcome and Measure: A prescription for a GLP-1 RA., Results: Of the 1 180 260 patients with T2D (median [IQR] age, 69 [59-76] years; 50.3% female; 57.7% White), 90 934 (7.7%) were treated with GLP-1 RA during the study period. From 2015 to 2019, the percentage of T2D patients treated with an GLP-1 RA increased from 3.2% to 10.7%. Among patients with T2D and ASCVD, use also increased but remained low (2.8%-9.4%). In multivariable analyses, lower rates of GLP-1 RA use were found among Asian (aOR, 0.59; 95% CI, 0.56-0.62), Black (adjusted odds ratio [aOR] 0.81; 95% CI, 0.79-0.83), and Hispanic (aOR, 0.91; 95% CI, 0.88-0.93) patients with T2D. Female sex (aOR, 1.22; 95% CI, 1.20-1.24) and higher zip code-linked median household incomes (>$100 000 [OR, 1.13; 95% CI, 1.11-1.16] and $50 000-$99 999 [OR, 1.07; 95% CI, 1.05-1.09] vs <$50 000) were associated with higher GLP-1 RA use. These results were similar to those found among patients with ASCVD., Conclusions and Relevance: In this cohort study of US patients with T2D, GLP-1 RA use increased, but remained low overall for treatment of T2D, particularly among patients with ASCVD who are likely to derive the most benefit. Asian, Black, and Hispanic patients and those with low income were less likely to receive treatment with a GLP-1 RA. Strategies to lower barriers to GLP-1 RA use, such as lower cost, are needed to prevent the widening of well-documented inequities in cardiovascular disease outcomes in the US., Competing Interests: Conflict of Interest Disclosures: Dr Essien reported grants from Department of Veterans Affairs (No. CDA-30-049) outside the submitted work. Dr Eneanya reported personal fees from Somatus and Davita outside the submitted work. Dr Luo reported grants from NCATS, NIDDK, and NIDA during the conduct of the study; and consulting fees from Health Action International and Alosa Health outside the submitted work. Dr Khatana reported grants from the National Heart, Lung, and Blood Institute (No. 5K23HL153772-02) and the American Heart Association (No. 20CDA35320251) during the conduct of the study. Dr Fanaroff reported grants from the American Heart Association and consulting fees from Intercept Pharmaceuticals outside the submitted work. Dr Giri reported consulting fees from AstraZeneca, Inari Medical, and Boston Scientific; and grants from Inari Medical and Boston Scientific, all outside the submitted work. No other disclosures were reported., (Copyright 2021 Eberly LA et al. JAMA Health Forum.)

Objective: We aimed to characterize outcomes associated with cangrelor administration used in an antiplatelet bridging strategy in real-world clinical scenarios within a large academic medical system., Background: Cangrelor has been used for antiplatelet bridging in perioperative settings or for patients unable to take oral medications. Prior studies in these settings have reported bleeding rates from 0%-40%., Methods: Patients were retrospectively identified via chart review and included if they were over 18 years old, had coronary or peripheral arterial stents, and had received at least 1 hour of cangrelor infusion during inpatient admission. The primary endpoint was Bleeding Academic Research Consortium (BARC) 3-5 bleeding during cangrelor infusion or within 48 hours of discontinuation; secondary endpoints were bleeding events defined by Thrombolysis in Myocardial Infarction (TIMI), Global Use of Strategies to Open Occluded Arteries (GUSTO), and International Society on Thrombosis and Hemostasis (ISTH) criteria, as well as BARC 2 bleeding., Results: Thirty-one patients met the inclusion criteria. Cangrelor indications were bridging to procedure in 22 patients (71.0%) and inability to take oral P2Y12 inhibitors in 9 patients (29.0%). Twenty-three patients (74.2%) were men, 11 patients (35.5%) were in cardiogenic shock, and 4 patients (12.9%) were on extracorporeal membrane oxygenation (ECMO) at the time of administration. No patients received cangrelor for routine percutaneous coronary intervention. Of the 31 patients, 13 (41.9%) had BARC 3-5 bleeding and 7 (22.6%) expired during hospitalization. All 4 patients on ECMO suffered BARC 3-5 bleeding., Conclusions: We reviewed the use of cangrelor for antiplatelet bridging in real-world clinical scenarios and observed higher rates of clinically significant bleeding than seen in other similar studies. Our study suggests careful consideration when using cangrelor in a sick patient population.

Background: Older adults with atrial fibrillation (AF) are often treated with the shortest possible duration of antiplatelet/anticoagulant therapy after myocardial infarction (MI) or percutaneous coronary intervention (PCI) due to concern for bleeding. However, the risk of recurrent MI or PCI prompting antiplatelet therapy extension is unknown in this population., Methods: Using the National Cardiovascular Data Registry linked to Medicare claims, we described the cumulative incidence of recurrent MI or PCI over a median of 7-year follow-up for patients ≥65 years old with AF discharged alive after acute MI between 2008 and 2017. We used pharmacy fill data to describe the proportion of patients filling prescriptions for both oral anticoagulants and P2Y 12 inhibitors for ≥50% of the indicated duration after MI or PCI., Results: Of 187 622 older patients discharged alive after MI, 50 539 (26.9%) had AF. Over a median of 7-year follow-up in patients with AF, the cumulative incidence was 14.5% for recurrent MI, 12.1% for PCI, 7.9% for stroke, and 9.5% for bleeding hospitalization. Among 7998 patients with AF and recurrent MI or PCI, 1668 (20.9%) had >1 MI or PCI during follow-up. Assuming each MI or PCI should be followed by 6 months of P2Y 12 inhibitor therapy, patients with AF who had a recurrent MI/PCI had a median estimated indication for antiplatelet/anticoagulant treatment of 287 days (194, 358), but filled both P2Y 12 inhibitor and oral anticoagulant for a median of 0 days (0, 21). In this cohort, 12.2% of patients filled prescriptions for both a P2Y 12 inhibitor and oral anticoagulant for ≥50% of the indicated duration., Conclusions: Older adults with AF and MI have high incidences of downstream recurrent MI or PCI requiring extended antiplatelet/anticoagulant therapy durations, yet many appear to be under-treated. These results highlight the need for better thrombosis prevention strategies in this group of patients.

Competing Interests: Funding Support and Author Disclosures This research was supported by the American College of Cardiology’s National Cardiovascular Data Registry. The National Cardiovascular Data Registry is an initiative of the American College of Cardiology Foundation. Dr Waldo has received unrelated investigator-initiated research support from Abiomed, Cardiovascular Systems Incorporated, Janssen, Merck Pharmaceuticals, National Institutes of Health, and Veterans Affairs Health Services Research and Development. Dr Yeh has received grants from AstraZeneca; has received consulting fees from Teleflex; and has served on advisory boards for Abbott, Boston Scientific, and Medtronic. Dr Fanaroff has received a career development grant and honoraria from the American Heart Association; and has received research funding from Boston Scientific. Dr Wang has received research grants to the Duke Clinical Research Institute from AstraZeneca, Bristol Myers Squibb, Cryolife, Portola, and Regeneron; and has received consulting honoraria from AstraZeneca. Dr Giri has served on advisory boards for Boston Scientific, Inari Medical, and AstraZeneca; and has received research funds to the institution from Boston Scientific, Recor Medical, and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objectives: The study sought to assess the proportion of patients in modern U.S. interventional practice that fulfilled criteria for enrollment in the ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial., Background: The ISCHEMIA trial, which enrolled patients with stable ischemic heart disease (SIHD), showed that revascularization improved angina symptoms with little effect on death or myocardial infarction., Methods: A cross-sectional analysis of the National Cardiovascular Data Registry CathPCI Registry (v5.0), including 1,662 hospitals, was performed. Patients undergoing percutaneous coronary intervention (PCI) for SIHD in routine clinical practice meeting ISCHEMIA trial inclusion criteria and those that did not were evaluated., Results: During the study period, 388,212 patients underwent PCI for SIHD, comprising 41.88% of all patients undergoing PCI during the study period. Of these, 125,302 (32.28%; 13.52% of all patients undergoing PCI) met criteria for enrollment in the ISCHEMIA trial. Among SIHD patients that did not meet criteria, 71,852 (18.51%) had SIHD with high-risk features (35.2% left main disease, 43.7% left ventricular systolic dysfunction, 16.8% end-stage renal disease), 67,159 (17.3%) had SIHD with negative or low-risk functional testing, and 123,899 (31.92%) either had no stress testing or did not have ischemic burden reported. At the median hospital, 32.1% (interquartile range: 23.5%-40.6%) of SIHD patients met criteria for enrollment in the ISCHEMIA trial, with these patients experiencing lower unadjusted in-hospital mortality rate than comparator groups who met exclusion criteria for the trial (0.11%) (P < 0.01 for all comparisons)., Conclusions: Among contemporary U.S. patients undergoing PCI for SIHD, 32.28% clearly met enrollment criteria for the ISCHEMIA trial. There was significant variation among individual centers in the proportion of SIHD patients meeting criteria for the ISCHEMIA trial., Competing Interests: Funding Support and Author Disclosures Dr Giri has received research funding to his institution from Inari Medical, Boston Scientific, and Recor Medical; and has served on the advisory board for Inari Medical, Boston Scientific, AstraZeneca, and Philips Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Despite the benefits of novel therapeutics, inequitable diffusion of new technologies may generate disparities. We examined the growth of transcatheter aortic valve replacement (TAVR) in the United States to understand the characteristics of hospitals that developed TAVR programs and the socioeconomic status of patients these hospitals served., Methods: We identified fee-for-service Medicare beneficiaries aged 66 years or older who underwent TAVR between January 1, 2012, and December 31, 2018, and hospitals that developed TAVR programs (defined as performing ≥10 TAVRs over the study period). We used linear regression models to compare socioeconomic characteristics of patients treated at hospitals that did and did not establish TAVR programs and described the association between core-based statistical area level markers of socioeconomic status and TAVR rates., Results: Between 2012 and 2018, 583 hospitals developed new TAVR programs, including 572 (98.1%) in metropolitan areas, and 293 (50.3%) in metropolitan areas with preexisting TAVR programs. Compared with hospitals that did not start TAVR programs, hospitals that did start TAVR programs treated fewer patients with dual eligibility for Medicaid (difference of -2.83% [95% CI, -3.78% to -1.89%], P ≤0.01), higher median household incomes (difference $2447 [95% CI, $1348-$3547], P =0.03), and from areas with lower distressed communities index scores (difference -4.02 units [95% CI, -5.43 to -2.61], P ≤0.01). After adjusting for the age, clinical comorbidities, race and ethnicity and socioeconomic status, areas with TAVR programs had higher rates of TAVR and TAVR rates per 100 000 Medicare beneficiaries were higher in core-based statistical areas with fewer dual eligible patients, higher median income, and lower distressed communities index scores., Conclusions: During the initial growth phase of TAVR programs in the United States, hospitals serving wealthier patients were more likely to start programs. This pattern of growth has led to inequities in the dispersion of TAVR, with lower rates in poorer communities.

Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel forms the backbone of secondary prevention in patients with acute coronary syndromes (ACS) or who undergo percutaneous coronary intervention (PCI), but in patients with atrial fibrillation (AF), oral anticoagulation (OAC) is superior to antiplatelet therapy for the prevention of stroke and systemic embolism. Patients with AF who undergo PCI or have an ACS event therefore have an indication for both OAC and DAPT, so-called triple antithrombotic therapy. However, observational analyses have shown that the annual rate of major bleeding on triple therapy exceeds 10%. For this reason, five major randomized clinical trials have compared double antithrombotic therapy with OAC and a P2Y 12 inhibitor versus triple therapy in patients with AF who underwent PCI or had an ACS event. Each of the trials showed that double antithrombotic therapy reduced the rate of major and clinically relevant non-major bleeding compared with triple therapy and was non-inferior for prevention of ischemic events, including cardiovascular death, myocardial infarction, or stroke. In the one trial that directly compared warfarin with a non-vitamin K antagonist oral anticoagulant (NOAC), apixaban reduced the rate of major or clinically relevant non-major bleeding compared with warfarin and was non-inferior with respect to prevention of ischemic events. As a result of these trials, consensus guidelines recommend that patients with AF who undergo PCI or have an ACS event should be treated with triple antithrombotic therapy (OAC + P2Y 12 inhibitor + aspirin) for 7 days or less, followed by double antithrombotic therapy (OAC + P2Y 12 inhibitor) for 6 to 12 months., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background Rates of major lower extremity amputation in patients with peripheral artery disease are higher in rural communities with markers of low socioeconomic status, but most Americans live in metropolitan areas. Whether amputation rates vary within US metropolitan areas is unclear, as are characteristics of high amputation rate urban communities. Methods and Results We estimated rates of major lower extremity amputation per 100 000 Medicare beneficiaries between 2010 and 2018 at the ZIP code level among ZIP codes with ≥100 beneficiaries. We described demographic characteristics of high and low amputation ZIP codes, and the association between major amputation rate and 3 ZIP code-level markers of socioeconomic status-the proportion of patients with dual eligibility for Medicaid, median household income, and Distressed Communities Index score-for metropolitan, micropolitan, and rural ZIP code cohorts. Between 2010 and 2018, 188 995 Medicare fee-for-service patients living in 31 391 ZIP codes with ≥100 beneficiaries had a major lower extremity amputation. The median (interquartile range) ZIP code-level number of amputations per 100 000 beneficiaries was 262 (75-469). Though nonmetropolitan ZIP codes had higher rates of major amputation than metropolitan areas, 78.2% of patients undergoing major amputation lived in metropolitan areas. Compared with ZIP codes with lower amputation rates, top quartile amputation rate ZIP codes had a greater proportion of Black residents (4.4% versus 17.5%, P <0.001). In metropolitan areas, after adjusting for clinical comorbidities and demographics, every $10 000 lower median household income was associated with a 4.4% (95% CI, 3.9-4.8) higher amputation rate, and a 10-point higher Distressed Communities Index score was associated with a 3.8% (95% CI, 3.4%-4.2%) higher amputation rate; there was no association between the proportion of patients eligible for Medicaid and amputation rate. These findings were comparable to the associations identified across all ZIP codes. Conclusions In metropolitan areas, where most individuals undergoing lower extremity amputation live, markers of lower socioeconomic status and Black race were associated with higher rates of major lower extremity amputation. Development of community-based tools for peripheral artery disease diagnosis and management targeted to communities with high amputation rates in urban areas may help reduce inequities in peripheral artery disease outcomes.

Background: Due to the high cost of left ventricular assist device (LVAD) therapy, payer type may be an important factor in determining eligibility. How payer type influences outcomes after LVAD implantation is unclear. We, therefore, aimed to study the association of health insurance payer type with outcomes after durable LVAD implantation., Methods: Using STS-INTERMACS (Society of Thoracic Surgeons-Interagency Registry for Mechanically Assisted Circulatory Support), we studied nonelderly adults receiving a durable LVAD from 2016 to 2018 and compared all-cause mortality and postindex hospitalization adverse event episode rate by payer type. Multivariable Fine-Gray and generalized linear models were used to compare the outcomes., Results: Of the 3251 patients included, 26.0% had Medicaid, 24.9% had Medicare alone, and 49.1% had commercial insurance. Compared with commercially insured patients, mortality did not differ for patients with Medicaid (subdistribution hazard ratio, 1.00 [95% CI, 0.75-1.34], P =0.99) or Medicare (subdistribution hazard ratio, 1.09 [95% CI, 0.84-1.41], P =0.52). Medicaid was associated with a significantly lower adjusted incidence rate (incidence rate ratio, 0.88 [95% CI, 0.78-0.99], P =0.041), and Medicare was associated with a significantly higher adjusted incidence rate (incidence rate ratio, 1.16 [95% CI, 1.03-1.30], P =0.011) of adverse event episodes compared with commercially insured patients., Conclusions: All-cause mortality after durable LVAD implantation did not differ significantly by payer type. Payer type was associated with the rate of adverse events, with Medicaid associated with a significantly lower rate, and Medicare with a significantly higher rate of adverse event episodes compared with commercially insured patients.

Importance: Sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduce deaths from cardiovascular conditions, hospitalizations for heart failure, and progression of kidney disease among patients with type 2 diabetes. Black individuals have a disproportionate burden of cardiovascular and chronic kidney disease (CKD). Adoption of novel therapeutics has been slower among Black and female patients and among patients with low socioeconomic status than among White or male patients or patients with higher socioeconomic status., Objective: To assess whether inequities based on race/ethnicity, gender, and socioeconomic status exist in SGLT2 inhibitor use among patients with type 2 diabetes in the US., Design, Setting, and Participants: This retrospective cohort study of commercially insured patients in the US was performed from October 1, 2015, to June 30, 2019, using the Optum Clinformatics Data Mart. Adult patients with a diagnosis of type 2 diabetes, including those with heart failure with reduced ejection fraction (HFrEF), atherosclerotic cardiovascular disease (ASCVD), or CKD, were evaluated in the analysis., Main Outcomes and Measures: Prescription of an SGLT2 inhibitor. Multivariable logistic regression models were used to assess the association of race/ethnicity, gender, and socioeconomic status with SGLT2 inhibitor use., Results: Of 934 737 patients with type 2 diabetes (mean [SD] age, 65.4 [12.9] years; 50.7% female; 57.6% White), 81 007 (8.7%) were treated with an SGLT2 inhibitor during the study period. Between 2015 and 2019, the percentage of patients with type 2 diabetes treated with an SGLT2 inhibitor increased from 3.8% to 11.9%. Among patients with type 2 diabetes and cardiovascular or kidney disease, the rate of SGLT2 inhibitor use increased but was lower than that among all patients with type 2 diabetes (HFrEF: 1.9% to 7.6%; ASCVD: 3.0% to 9.8%; CKD: 2.1% to 7.5%). In multivariable analyses, Black race (adjusted odds ratio [aOR], 0.83; 95% CI, 0.81-0.85), Asian race (aOR, 0.94; 95% CI, 0.90-0.98), and female gender (aOR, 0.84; 95% CI, 0.82-0.85) were associated with lower rates of SGLT2 inhibitor use, whereas higher median household income (≥$100 000: aOR, 1.08 [95% CI, 1.05-1.10]; $50 000-$99 999: aOR, 1.05 [95% CI, 1.03-1.07] vs <$50 000) was associated with a higher rate of SGLT2 inhibitor use. These results were similar among patients with HFrEF, ASCVD, and CKD., Conclusions and Relevance: In this cohort study, use of an SGLT2 inhibitor treatment increased among patients with type 2 diabetes from 2015 to 2019 but remained low, particularly among patients with HFrEF, CKD, and ASCVD. Black and female patients and patients with low socioeconomic status were less likely to receive an SGLT2 inhibitor, suggesting that interventions to ensure more equitable use are essential to prevent worsening of well-documented disparities in cardiovascular and kidney outcomes in the US.

Background: Patients with atrial fibrillation (AF) who have undergone mitral valve repair are at risk for thromboembolic strokes. Prior to 2019, only vitamin K antagonists were recommended for patients with AF who had undergone mitral valve repair despite the introduction of direct oral anticoagulants (DOAC) in 2010., Objective: To characterize the use of anticoagulants in patients with AF who underwent surgical mitral valve repair (sMVR) or transcatheter mitral valve repair (tMVR)., Methods: We performed a retrospective cohort analysis of patients with AF undergoing sMVR or tMVR between 04/2014 and 12/2018 using Optum's de-identified Clinformatics® Data Mart Database. We identified anticoagulants prescribed within 90 days of discharge from hospitalization., Results: Overall, 1997 patients with AF underwent valve repair: 1560 underwent sMVR, and 437 underwent tMVR. The mean CHA 2 DS 2 -VASc score among all patients was 4.1 (SD 1.9). The overall use of anticoagulation was unchanged between 2014 (72.2%) and 2018 (70.0%) (P = .49). Among patients who underwent sMVR or tMVR between April 2014 and December 2018, the use of VKA therapy decreased from 62.9% to 32.1% (P < .01 for trend) and the use of DOACs increased from 12.4% to 37.3% (P < .01 for trend)., Conclusions: Among patients with AF who underwent sMVR or tMVR between 2014 and 2018, roughly 30% of patients were not treated with any anticoagulant within 90 days of discharge, despite an elevated stroke risk in the cohort. The rate of DOAC use increased steadily over the study period but did not significantly increase the rate of overall anticoagulant use in this high-risk cohort., (Copyright © 2020 Elsevier Inc. All rights reserved.)