Effect of Gamification, Financial Incentives, or Both to Increase Physical Activity Among Patients at High Risk of Cardiovascular Events: The BE ACTIVE Randomized Controlled Trial.

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.

Association Between Diagnosis-to-Limb Revascularization Time and Clinical Outcomes in Outpatients With Chronic Limb-Threatening Ischemia: Insights From the CLIPPER Cohort.

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.

Two randomized controlled trials of nudges to encourage referrals to centralized pharmacy services for evidence-based statin initiation in high-risk patients: Rationale and design of the SUPER LIPID program.

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.

Optimal Medical Therapy for Chronic Coronary Disease in 2024: Focus on Antithrombotic Therapy.

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.

Gamification-augmented home-based exercise for peripheral artery disease: Rationale and design of the GAMEPAD Study.

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.

Enrollment of Older Patients, Women, and Racial and Ethnic Minority Individuals in Valvular Heart Disease Clinical Trials: A Systematic Review.

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.

Association between racial residential segregation and Black-White disparities in cardiovascular disease mortality.

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.

Racial Differences in Presentation and Outcomes After Peripheral Arterial Interventions: Insights From the NCDR-PVI Registry.

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.

A randomized controlled trial of gamification, financial incentives, or both to increase physical activity among patients with elevated risk for cardiovascular disease: rationale and design of the be active study.

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.

Racial, Ethnic, and Socioeconomic Inequities in Access to Left Atrial Appendage Occlusion.

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.

Feasibility and outcomes from using a commitment device and text message reminders to increase adherence to time-restricted eating: A randomized trial.

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/m2. 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.

Characteristics of Clinical Trial Sites for Novel Transcatheter Mitral and Tricuspid Valvular Therapies.

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.

COVID-19 Thrombotic Complications and Therapeutic Strategies.

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.