Publications

2016

Collaborators, GBD 2015 Risk Factors. (2016) 2016. “Global, Regional, and National Comparative Risk Assessment of 79 Behavioural, Environmental and Occupational, and Metabolic Risks or Clusters of Risks, 1990-2015: A Systematic Analysis for the Global Burden of Disease Study 2015.”. Lancet (London, England) 388 (10053): 1659-1724. https://doi.org/10.1016/S0140-6736(16)31679-8.
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BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context.

METHODS: We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI).

FINDINGS: Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6-58·8) of global deaths and 41·2% (39·8-42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa.

INTERPRETATION: Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden.

FUNDING: Bill & Melinda Gates Foundation.

Chen, Shu, Enying Gong, Dhruv S Kazi, Ann B Gates, Kamilu Musa Karaye, Nicolas Girerd, Rong Bai, et al. (2016) 2016. “Development of a Mobile Phone-Based Intervention to Improve Adherence to Secondary Prevention of Coronary Heart Disease in China.”. Journal of Medical Engineering & Technology 40 (7-8): 372-82.
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Coronary heart disease (CHD) is a major disease burden globally and in China, but secondary prevention among CHD patients remains insufficient. Mobile health (mHealth) technology holds promise for improving secondary prevention but few previous studies included both provider-facing and patient-directed measures. We conducted a physician needs assessment survey (n = 59), physician interviews (n = 6), one focus group and a short cellphone message validation survey (n = 14) in Shanghai and Hainan, China. Based on these results, we developed a multifaceted mHealth intervention that includes: (1) a provider-facing bilingual mobile app guiding prescription of evidence-based medications for secondary prevention and (2) a patient-directed short messaging system automatically sending reminders to patients regarding medication adherence and lifestyle changes (4-5 messages per week for 12 weeks). This combined intervention has the potential to improve secondary prevention of CHD and to be adapted to other countries and healthcare conditions.

Collaborators, GBD 2015 DALYs and HALE. (2016) 2016. “Global, Regional, and National Disability-Adjusted Life-Years (DALYs) for 315 Diseases and Injuries and Healthy Life Expectancy (HALE), 1990-2015: A Systematic Analysis for the Global Burden of Disease Study 2015.”. Lancet (London, England) 388 (10053): 1603-58. https://doi.org/10.1016/S0140-6736(16)31460-X.
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BACKGROUND: Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development.

METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate.

FINDINGS: Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2·9 years (95% uncertainty interval 2·9-3·0) for men and 3·5 years (3·4-3·7) for women, while HALE at age 65 years improved by 0·85 years (0·78-0·92) and 1·2 years (1·1-1·3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs.

INTERPRETATION: Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum.

FUNDING: Bill & Melinda Gates Foundation.

Collaborators, GBD 2015 Maternal Mortality. (2016) 2016. “Global, Regional, and National Levels of Maternal Mortality, 1990-2015: A Systematic Analysis for the Global Burden of Disease Study 2015.”. Lancet (London, England) 388 (10053): 1775-1812. https://doi.org/10.1016/S0140-6736(16)31470-2.
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BACKGROUND: In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015.

METHODS: We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specific reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility.

FINDINGS: Only ten countries achieved MDG 5, but 122 of 195 countries have already met SDG 3.1. Geographical disparities widened between 1990 and 2015 and, in 2015, 24 countries still had a maternal mortality ratio greater than 400. The proportion of all maternal deaths occurring in the bottom two SDI quintiles, where haemorrhage is the dominant cause of maternal death, increased from roughly 68% in 1990 to more than 80% in 2015. The middle SDI quintile improved the most from 1990 to 2015, but also has the most complicated causal profile. Maternal mortality in the highest SDI quintile is mostly due to other direct maternal disorders, indirect maternal disorders, and abortion, ectopic pregnancy, and/or miscarriage. Historical patterns suggest achievement of SDG 3.1 will require 91% coverage of one antenatal care visit, 78% of four antenatal care visits, 81% of in-facility delivery, and 87% of skilled birth attendance.

INTERPRETATION: Several challenges to improving reproductive health lie ahead in the SDG era. Countries should establish or renew systems for collection and timely dissemination of health data; expand coverage and improve quality of family planning services, including access to contraception and safe abortion to address high adolescent fertility; invest in improving health system capacity, including coverage of routine reproductive health care and of more advanced obstetric care-including EmOC; adapt health systems and data collection systems to monitor and reverse the increase in indirect, other direct, and late maternal deaths, especially in high SDI locations; and examine their own performance with respect to their SDI level, using that information to formulate strategies to improve performance and ensure optimum reproductive health of their population.

FUNDING: Bill & Melinda Gates Foundation.

Ben-Yehuda, Ori, Dhruv S Kazi, Machaon Bonafede, Sally W Wade, Susanne F Machacz, Leslie A Stephens, Mark A Hlatky, and John B Hernandez. (2016) 2016. “Angina and Associated Healthcare Costs Following Percutaneous Coronary Intervention: A Real-World Analysis from a Multi-Payer Database.”. Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions 88 (7): 1017-24. https://doi.org/10.1002/ccd.26365.
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OBJECTIVES: To study the contemporary, real-world clinical and economic burden associated with angina after percutaneous coronary intervention (PCI).

BACKGROUND: Angina adversely affects quality of life and medical costs, yet data on real-world prevalence of angina following PCI and its associated economic consequences are limited.

METHODS: In a multi-payer administrative claims database, we identified adults with incident inpatient PCI admissions between 2008 and 2011 who had at least 12 months of continuous medical and pharmacy benefits before and after the procedure. Patients were followed for up to 36 months. Using claims, we ascertained post-PCI outcomes: angina or chest pain, acute myocardial infarction, acute coronary syndrome, repeat PCI, healthcare service utilization, and costs.

RESULTS: Among 51,710 study patients (mean age 61.8, 72% male), post-PCI angina or chest pain was present in 28% by 12 months and 40% by 36 months. Compared with patients who did not experience chest pain, angina or ACS, total healthcare costs in the first year after the index PCI were 1.8 times greater for patients with angina or chest pain ($32,437 vs. $17,913, P < 0.001). These cost differentials continued to 36 months.

CONCLUSIONS: Angina after PCI is a frequent and expensive outcome. Further research is needed to identify risk factors and potentially improve outcomes for post-PCI angina. © 2016 Wiley Periodicals, Inc.

Balsari, Satchit, Gregg Greenough, Dhruv Kazi, Aaron Heerboth, Shraddha Dwivedi, and Jennifer Leaning. (2016) 2016. “Public Health Aspects of the World’s Largest Mass Gathering: The 2013 Kumbh Mela in Allahabad, India.”. Journal of Public Health Policy 37 (4): 411-27. https://doi.org/10.1057/s41271-016-0034-z.
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India's Kumbh Mela remains the world's largest and longest mass gathering. The 2013 event, where participants undertook a ritual bath, hosted over 70 million Hindu pilgrims during 55 days on a 1936 hectare flood plain at the confluence of the Yamuna and Ganga Rivers. On the holiest bathing days, the population surged. Unlike other religious, cultural, and sports mass gatherings, the Kumbh Mela's administration cannot estimate or limit the participant number. The event created serious and uncommon public health challenges: initiating crowd safety measures where population density and mobility directly contact flowing bodies of water; providing water, sanitation, and hygiene to a population that frequently defecates in the open; and establishing disease surveillance and resource use measures within a temporary health delivery system. We review the world's largest gathering by observing first-hand the public health challenges, plus the preparations for and responses to them. We recommend ways to improve preparedness.

2015

Collaborators, GBD 2013 Mortality and Causes of Death. (2015) 2015. “Global, Regional, and National Age-Sex Specific All-Cause and Cause-Specific Mortality for 240 Causes of Death, 1990-2013: A Systematic Analysis for the Global Burden of Disease Study 2013.”. Lancet (London, England) 385 (9963): 117-71. https://doi.org/10.1016/S0140-6736(14)61682-2.
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BACKGROUND: Up-to-date evidence on levels and trends for age-sex-specific all-cause and cause-specific mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries.

METHODS: We estimated age-sex-specific all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specific causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions.

FINDINGS: Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute differences between countries decreased but relative differences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative differences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100,000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions.

INTERPRETATION: For most countries, the general pattern of reductions in age-sex specific mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.

FUNDING: Bill & Melinda Gates Foundation.

  • Kazi, Dhruv S, Joshua A Beckman, Regina M Benjamin, Grace Firestone, Janay C Johnson, Mark B McClellan, Neil Meltzer, et al. (2026) 2026. “Health Care Affordability in the United States, From Crisis to Action: A Presidential Advisory From the American Heart Association.”. Circulation. https://doi.org/10.1161/CIR.0000000000001442.
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    The United States is facing a growing health care affordability crisis. In 2024, national health expenditures totalled $5.3 trillion, or $15 474 per person, accounting for 18.0% of the U.S. economy. Spending on health care continues to rise, propelled by high prices for services, drugs, and devices; growing administrative complexity; chronic underinvestment in prevention, primary care, and public health; and the mounting burden of chronic conditions such as cardiovascular disease. Patients, even those with insurance, frequently face financial hardship, delayed or foregone care, and medical debt because of gaps in coverage and inadequate consumer protections. Addressing this crisis will require coordinated action across the health care system, guided by evidence and a commitment to shared responsibility among key stakeholders. This Presidential Advisory from the American Heart Association draws on interviews and listening sessions with patients, clinicians, payers, employers, health system leaders, and public health experts to examine the many dimensions of affordability and offer a practical framework for action. The Advisory presents 5 core principles to guide efforts to address the affordability crisis: ensuring access to high-quality care without financial hardship; minimizing cost sharing for high-value services; creating shared accountability across the health care system; investing in the workforce, infrastructure, and data systems needed to support progress; and addressing the social and structural factors that make care less affordable for many communities. The evidence, tools, and expertise to combat the health care affordability crisis already exist. What is needed now is the collective will to act.

  • Decker, Sérgio R R, Ana Paula Beck da S Etges, André Zimerman, Fernanda D Alves, Caique M Ternes, Juliana S Santos, Leandro Zimerman, et al. (2025) 2025. “Conduction System Pacing Vs Biventricular Pacing in Chronic Heart Failure: Protocol for the Economic Analysis of the PhysioSync-HF Trial.”. Arquivos Brasileiros de Cardiologia 122 (12): e20250254. https://doi.org/10.36660/abc.20250254.
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    BACKGROUND: Conduction system pacing (CSP) has emerged as an alternative to biventricular pacing (BVP) for cardiac resynchronization therapy (CRT), with potential clinical benefits and lower costs. PhysioSync-HF is a multicenter, randomized trial comparing these strategies from both clinical and economic perspectives in patients with heart failure with reduced ejection fraction (HFrEF).

    OBJECTIVE: To describe the rationale and design of the trial-based economic evaluation embedded within the PhysioSync-HF trial.

    METHODS: The PhysioSync-HF trial enrolled 179 patients with 1-year follow-up. Procedural cost data will be collected using a time-driven activity-based costing approach. Costs associated with the device, adverse clinical events, and ambulatory care during follow-up will be estimated using resource-based accounting methods. Appropriate methods will address missing data, and statistical analyses will account for the skewed distribution of cost variables.

    RESULTS: The primary economic outcome is the between-group difference in total direct medical costs per patient over the 1-year follow-up (CSP vs BVP). Secondary outcomes include component-level cost breakdowns of direct medical expenses and a budget impact analysis estimating the annual effect on Brazil's health care system if all eligible patients received CSP instead of BVP.

    CONCLUSION: By leveraging a multicenter cardiovascular trial to measure costs of CSP versus BVP, this economic evaluation aims to identify cost-saving opportunities that could expand equitable access to CRT for individuals with HFrEF in Brazil, while providing insights relevant to other health care settings worldwide.

    TRIAL REGISTRATION: NCT05572736.

  • Varghese, Merilyn S, Ling Han, Parul U Gandhi, Melissa Skanderson, Wen-Chih Wu, Kariann R Drwal, Matthew M Burg, et al. (2026) 2026. “Cardiac Rehabilitation Utilization Among Veterans: A Sex-Based Analysis.”. JACC. Advances 5 (3): 102615. https://doi.org/10.1016/j.jacadv.2026.102615.
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    BACKGROUND: Veterans are at an increased cardiovascular risk compared to age- and sex-matched non-Veterans. Cardiac rehabilitation (CR) can improve outcomes in cardiovascular disease, but its use in men and women Veterans is not well understood.

    OBJECTIVES: This study aimed to examine CR participation by sex and socioeconomic status among Veterans.

    METHODS: The authors conducted a retrospective cohort study from January 1, 2021, to December 31, 2023, using a national electronic health record database. The primary outcome was participation in at least 1 CR session among patients within 1 year of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery. Multivariable logistic regression models accounted for patient-level (demographics, medical/psychiatric comorbidities) and community-level factors. Area deprivation indices (ADIs) (analyzed as quartiles) assessed socioeconomic status.

    RESULTS: Among 82,496 CR-eligible Veterans (3.6% women), CR participation was low (10.4%) and similar by sex (women = 10.2%, men = 10.4%). Women Veterans did not differ significantly in CR participation compared to men Veterans after adjusting for patient-level and community-level characteristics, including age, race, cardiac and comorbidities, mental health risk factors, rural-urban status, and ADI (adjusted OR: 0.90; 95% CI: 0.79-1.03; P = 0.121). Veterans in the most deprived ADI quartile were less likely to participate vs the least deprived quartile (adjusted OR: 0.82; 95% CI: 0.75-0.89; P < 0.001).

    CONCLUSIONS: CR participation among U.S. Veterans remains low, far below that of the Medicare population (10.4% vs 28%), with no significant differences in initiation by sex. However, low socioeconomic status is associated with decreased uptake. Further research is needed to explore innovative, Veteran-specific CR delivery models.

  • Hennessy, Susan, Joanne Penko, Brandon K Bellows, Pamela G Coxson, Ross Boylan, Kendra D Sims, Alexis Beatty, et al. (2026) 2026. “Cost-Effectiveness of Semaglutide for Secondary Prevention of Cardiovascular Disease in US Adults.”. JAMA Cardiology 11 (3): 229-38. https://doi.org/10.1001/jamacardio.2025.5243.
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    IMPORTANCE: Semaglutide reduces the risk of major adverse cardiovascular events (MACE) in adults with overweight or obesity and cardiovascular disease (CVD) but without diabetes. The cost-effectiveness and budget impact of semaglutide therapy could inform ongoing Medicare price negotiations but are uncertain.

    OBJECTIVE: To evaluate the cost-effectiveness of semaglutide for secondary prevention of CVD and potential effect on US health care spending.

    DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort simulation study used the CVD Policy Model, a validated simulation model of CVD outcomes and costs in the US, to evaluate lifetime cost-effectiveness of semaglutide. The addition of lifetime treatment with weekly subcutaneous semaglutide to usual care compared with usual care alone in US adults age 45 years or older, with a body mass index (calculated as weight in kilograms divided by height in meters squared) of 27 or higher, and history of myocardial infarction or stroke, without diabetes were evaluated. The model incorporated annual semaglutide cost of $8604 (2023 US price net of rebates and discounts) and adopted a health-system perspective. Sensitivity analyses explored uncertainty. These data were analyzed from January 2024 and June 2025.

    EXPOSURE: Semaglutide and usual care compared with usual care alone.

    MAIN OUTCOMES AND MEASURES: Main outcomes were lifetime MACE (cardiovascular death, myocardial infarction, or stroke), incremental cost per quality-adjusted life-year (QALY), and change in annual US health care spending.

    RESULTS: Adding semaglutide to usual care in the estimated 4 million US adults without diabetes eligible for secondary prevention of CVD is projected to avert 358 400 MACE at a cost of $148 100 per QALY gained (95% uncertainty interval, $127 100-$173 400). The mean age of this cohort was 66 years and 55% were male and 45% were female. Treatment with semaglutide was projected to increase annual health care spending by $23 billion. Semaglutide would be cost-effective at a threshold of $120 000 per QALY gained if the annual cost were lowered an additional 18% to $7055. Semaglutide is cost-effective for this indication at the cash price currently available to self-paying customers ($5988; incremental cost-effectiveness ratio, $99 600 per QALY gained).

    CONCLUSIONS AND RELEVANCE: Semaglutide for secondary prevention of CVD in US adults with overweight or obesity but without diabetes is projected to yield meaningful health benefits. Lowering annual drug costs by 18% from $8604 to $7055-or making the current cash price available to all patients-would make semaglutide cost-effective at $120 000 per QALY gained.

  • Mounsey, Louisa A, Mandana Chitsazan, Ivy Shi, Pedro H Ribeiro, Juhi K Parekh, Athar Roshandelpoor, Chiadi Ndumele, et al. (2026) 2026. “Cardiovascular-Kidney-Metabolic Medication Eligibility Across National Survey, Community-Based, and Ambulatory Healthcare Samples.”. JAMA Cardiology 11 (3): 250-58. https://doi.org/10.1001/jamacardio.2025.5305.
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    IMPORTANCE: The prevalence of obesity and cardiovascular-kidney-metabolic (CKM) syndrome continues to rise. Indications for novel CKM therapies, including glucagonlike peptide 1 receptor agonists (GLP-1RAs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), and nonsteroidal mineralocorticoid antagonists (nsMRAs) continue to expand, yet the proportion of adults meeting expanded indications, including for multiple medications remains unclear.

    OBJECTIVE: To examine proportion of adults meeting US Food and Drug Administration (FDA)-approved indications for GLP1-RAs, SGLT2is, and nsMRAs across national survey, community-based, and ambulatory health care samples.

    DESIGN, SETTING, AND PARTICIPANTS: This study used a representative cross-sectional survey of US adults (National Health and Nutrition Examination Survey [NHANES], weighted 245 million; mean [SD] age, 47 [18] years; 126.8 million [52%] female), 5 pooled community-based cohort studies (the Framingham Heart Study, the Multi-Ethnic Study of Atherosclerosis, the Prevention of Renal and Vascular Endstage Disease Study, the Atherosclerosis Risk in Communities Study, and the Cardiovascular Health Study; n = 30 929; mean [SD] age, 63 [14] years; 16 749 [54%] female), and 2 ambulatory health care samples (the Beth Israel Deaconess Medical Center cohort [BIDMC], n = 84 714; mean [SD] age, 46 [17] years; 51 113 [60%] female] and the Mass General Brigham cohort [MGB], n = 362 485; mean [SD] age, 48 [17] years; 227 206 [61%] female). Data were analyzed from November 2024 to November 2025.

    EXPOSURES: FDA-approved indications for GLP-1RAs, SGLT2is, and nsMRAs.

    MAIN OUTCOMES AND MEASURES: Medication class eligibility within each study sample.

    RESULTS: The proportion of individuals who met current FDA-approved indications for 1 or more CKM medication was 60% in NHANES (representing 148 million US adults), 61% in the pooled cohorts, 42% in the BIDMC ambulatory cohort, and 46% in the MGB ambulatory cohort. Eligibility for GLP-1RA therapy was most common, with 56% (representing 137.1 million US adults) in NHANES, 49% in the pooled cohorts, 41% in the BIDMC cohort, and 46% in the MGB cohort. This was followed by SGLT2i therapy (24% [57.9 million] in NHANES, 33% in the pooled cohorts, 14% for both BIDMC and MGB) and nsMRA (5% [11.7 million] in NHANES, 5% in the pooled cohorts, and 1% to 2% in ambulatory samples). Overlapping eligibility for multiple classes was common, with 12% to 17% for GLP1-RA and SGLT2i therapies and 1% to 5% for all 3 classes (an estimated 11.7 million US adults in NHANES).

    CONCLUSIONS AND RELEVANCE: This study found that up to 61% of adults met FDA-approved indications for at least 1 of 3 novel CKM therapy classes. This represents an estimated 148 million US adults, including 11.7 million US adults with potential FDA indications for triple therapy, highlighting the urgent need to optimize implementation and utilization of CKM syndrome therapies.

  • Mukhopadhyay, Amrita, Samrachana Adhikari, Xiyue Li, Dhruv S Kazi, Adam N Berman, Ian Kronish, Carine Hamo, et al. (2026) 2026. “Prior Authorization Requirements and Prescription Fill Patterns Among Patients With Heart Failure.”. JACC. Advances 5 (2): 102583. https://doi.org/10.1016/j.jacadv.2025.102583.
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    BACKGROUND: Prior authorizations could hinder the filling of life-saving heart failure (HF) medications, such as angiotensin receptor neprilysin inhibitors (ARNIs) and sodium glucose cotransporter 2 inhibitors (SGLT2is).

    OBJECTIVES: The aim of the study was to determine whether prior authorizations were associated with delayed or decreased filling for ARNI and SGLT2i.

    METHODS: This was a retrospective cohort study using electronic health record, pharmacy fill, and neighborhood-level data from a large, academic health system. We included patients with HF and a new prescription for ARNI or SGLT2i between April 1, 2021, and April 30, 2023, and assessed for presence of prior authorization requirement. Outcomes included days to first fill and never filling the prescription. Analyses were conducted using inverse probability weighting methods.

    RESULTS: Among 2,183 patients, 12.2% (152/1,243) and 14.3% (165/1,150) had a prior authorization requirement for ARNI or SGLT2i, respectively. Patients requiring prior authorization tended to be younger, identify as non-Hispanic Black or Hispanic, have non-Medicare insurance, and have fewer comorbidities. In weighted models, patients requiring prior authorization took 3.03 (95% CI: 2.16-4.25) times longer to fill ARNI, 6.75 (95% CI: 4.44-10.3) times longer to fill SGLT2i, and were 2.23 (95% CI: 1.37-3.65) times more likely to never fill SGLT2i prescriptions (all P < 0.001).

    CONCLUSIONS: Prior authorization requirements were more common for patients identifying as Black or Hispanic and were associated with decreased and delayed filling of ARNI and SGLT2i. Our findings highlight an important barrier to mortality-reducing, guideline-recommended medications for HF.

  • Palaniappan, Latha P, Norrina B Allen, Zaid I Almarzooq, Cheryl A M Anderson, Pankaj Arora, Christy L Avery, Carissa M Baker-Smith, et al. (2026) 2026. “2026 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.”. Circulation 153 (9): e275-e906. https://doi.org/10.1161/CIR.0000000000001412.
    Publisher's Version
    Publisher's Version

    BACKGROUND: The American Heart Association annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and cardiovascular-kidney-metabolic syndrome) that contribute to cardiovascular health. The 2026 Heart Disease and Stroke Statistics Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

    METHODS: The American Heart Association, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistics Update with review of published literature through the year before writing. The 2026 Statistics Update is the product of a full year's worth of effort in 2025 by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes a new chapter on cardiovascular-kidney-metabolic syndrome, as well as an expanded chapter on tobacco and nicotine use and exposure.

    RESULTS: Each of the chapters in the Statistics Update focuses on a different topic related to heart disease and stroke statistics.

    CONCLUSIONS: The Statistics Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

  • Decker, Sérgio R R, Richard S Chaudhary, Kosuke Inoue, Yang Song, Chiadi E Ndumele, Sadiya S Khan, and Dhruv S Kazi. (2026) 2026. “Socioeconomic Factors and Initiation of Semaglutide or Tirzepatide Among Medicare Beneficiaries With Type 2 Diabetes.”. Diabetes Care 49 (2): 277-81. https://doi.org/10.2337/dc25-1619.
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    OBJECTIVE: Identifying social and economic factors associated with initiation of semaglutide or tirzepatide may inform strategies to support equitable uptake.

    RESEARCH DESIGN AND METHODS: A cross-sectional study was conducted using 100% of Medicare claims of patients ≥65 years with type 2 diabetes mellitus (T2DM). The outcome was initiation of semaglutide or tirzepatide. We calculated adjusted odds ratios (aORs) for each exposure (self-reported race and ethnicity, dual enrollment in Medicare and Medicaid, rurality, and social vulnerability index), accounting for demographic and clinical characteristics.

    RESULTS: Among 13,922,387 patients with T2DM, 673,776 (4.8%) initiated semaglutide or tirzepatide in 2023. Minoritized racial and ethnic identity (e.g., non-Hispanic Black compared with White; aOR 0.72; 95% CI 0.71-0.72), dual enrollment (aOR 0.90; 0.89-0.91), and residence in the most versus least vulnerable socially vulnerable neighborhoods (aOR 0.93; 0.92-0.93) were associated with lower initiation.

    CONCLUSIONS: Minoritized racial and ethnic identity and adverse socioeconomic factors were associated with lower odds of initiation among Medicare beneficiaries with T2DM.

  • Bellows, Brandon K, Yiyi Zhang, Natalia Ruiz-Negrón, Dhruv S Kazi, Amit Khera V, Jessica G Woo, Elaine M Urbina, et al. (2025) 2025. “Familial Hypercholesterolemia Screening in Childhood and Early Adulthood: A Cost-Effectiveness Study.”. JAMA. https://doi.org/10.1001/jama.2025.20648.
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    IMPORTANCE: Heterozygous familial hypercholesterolemia (FH), a genetic condition, results in lifelong increased low-density lipoprotein cholesterol (LDL-C) and increases lifetime cardiovascular disease (CVD) risk. Most individuals with FH remain undiagnosed, so early FH identification and treatment could lower CVD burden.

    OBJECTIVE: To evaluate the projected cost-effectiveness of population sequential FH screening (lipid testing followed by genetic testing after a high LDL-C measurement) at 10 or 18 years of age.

    DESIGN, SETTING, AND PARTICIPANTS: The CVD Policy Model, a validated discrete event simulation of CVD risk factor management and CVD outcomes in National Health and Nutrition Examination Survey participants, was used to simulate lifetime health and economic outcomes from a health care sector perspective for a hypothetical cohort of 4.2 million US 10-year-olds. Individual characteristics and health care processes informed CVD events (coronary heart disease or stroke) and survival probabilities. Model inputs included national data sources, clinical trials, pooled longitudinal cohort studies, and published literature.

    INTERVENTIONS: Usual care assumed only opportunistic lipid testing and LDL-C and CVD risk-guided treatment. When added to usual care, sequential FH screening strategies examined combinations of childhood (age 10 years) or early adulthood (age 18 years) screening with 3 LDL-C thresholds (≥130 mg/dL, ≥160 mg/dL, or ≥190 mg/dL) to select patients for genetic testing.

    MAIN OUTCOMES AND MEASURES: Primary outcomes were direct health care costs (2021 US dollars), quality-adjusted life-years (QALYs), and an incremental cost-effectiveness ratio (ICER). Future costs and QALYs were discounted 3% annually. Strategies with an ICER of less than $100 000 per QALY gained were considered cost-effective.

    RESULTS: For the simulated cohort, usual care would lead to 3 118 000 (95% uncertainty interval, 3 061 000-3 192 000) total lifetime CVD events, with 16 182 (95% uncertainty interval, 15 683-16 827) among those with FH. Childhood FH screening could avert between 1385 and 1820 CVD events (<0.1% reduction in overall population), and early adulthood FH screening could avert between 1154 and 1448 CVD events (<0.1% reduction). While effective, no FH screening strategies were cost-effective relative to usual care; screening at age 18 years using an LDL-C threshold of 190 mg/dL or greater had the lowest ICER, at $289 700 per QALY gained. Sequential FH screening could become cost-effective vs usual care if lifetime lipid monitoring plus lifestyle therapy increased after a high screening LDL-C result, including for patients with non-FH dyslipidemias.

    CONCLUSIONS AND RELEVANCE: Sequential FH screening in childhood or early adulthood could be effective but not cost-effective vs usual care. However, sequential FH screening could become cost-effective under highly optimistic assumptions about increased lifestyle therapy and increased lifetime lipid monitoring for patients with non-FH dyslipidemias.

  • Khoong, Elaine C, Hyunjin Cindy Kim, Junhong Li, Jorge Larreynaga, Isabel Luna, Andersen Yang, Dhruv S Kazi, et al. (2025) 2025. “Implementation Strategies for Self-Measured Blood Pressure Monitoring in Racially and Ethnically Diverse Populations (InSPIRED): A Study Protocol.”. Contemporary Clinical Trials, 108101. https://doi.org/10.1016/j.cct.2025.108101.
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    INTRODUCTION: Self-measured blood pressure (SMBP) monitoring with clinical support is an evidence-based practice to improve hypertension control. However, it can be challenging to implement in safety-net systems that disproportionately serve low-income and/or racial/ethnic minority populations at risk of worse hypertension outcomes. We therefore propose a hybrid effectiveness-implementation trial to evaluate the effectiveness of multi-level implementation strategies to increase the use of SMBP monitoring in two urban safety-net systems.

    METHODS: We will conduct a patient-level randomized controlled trial with 330 English-, Spanish-, and Chinese (Cantonese)-speaking patients with uncontrolled hypertension across six study sites with patients randomized to a low-intensity (SMBP education, text message education and reminders) vs high-intensity intervention (adds group classes and engagement of identified caregivers). To support increased use of SMBP data by the clinical team, we will concurrently deliver a staggered roll-out of a clinic-level implementation strategy (clinic education, shadowing, auditing with feedback, and optimization of electronic health record [EHR] use).

    RESULTS: The primary outcomes will be clinic-measured systolic BP (SBP) among enrolled participants for the patient-level intervention and among all patients assigned to the clinic for the clinic-level intervention. We will additionally collect secondary clinical outcomes (BP control, home SBP), implementation outcomes (adoption, reach, and costs), and patient-reported outcomes (patient activation).

    DISCUSSION: The results of this trial will address gaps in identifying cost-conscious implementation strategies for increasing adoption of SMBP in safety-net systems with the overarching goal of improving blood pressure control in low-income, diverse patient populations. Trial registration NCT, NCT06871462. Registered 4 March 2025, https://clinicaltrials.gov/study/NCT06871462.

  • Kazi, Dhruv S, Abdul R Abdullah, Suzanne Arnold V, Anirban Basu, Brandon K Bellows, Khadijah Breathett, Derek S Chew, et al. (2025) 2025. “2025 AHA/ACC Statement on Cost/Value Methodology in Clinical Practice Guidelines (Update From 2014 Statement): A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.”. Journal of the American College of Cardiology. https://doi.org/10.1016/j.jacc.2025.05.009.
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    AIM: The "2025 AHA/ACC Statement on Cost/Value Methodology in Clinical Practice Guidelines (Update From 2014 Statement)" describes a systematic approach for consistent implementation of "economic value statements" across ACC/AHA guidelines. It updates the cost-effectiveness threshold and proposes a new level of certainty framework that summarizes the strength of the available evidence. Additionally, it describes how cost-effectiveness analyses (CEAs) can help advance equity in population cardiovascular health.

    METHODS: A focused literature search was conducted from January 9, 2024, to February 2, 2024, encompassing English-language publications related to CEA methodology in PubMed, EMBASE, and the Cochrane Library, with publication dates ranging from 1973 to the present. Additional relevant studies published during the writing process (through June 25, 2024) were also considered by the writing committee.

    STRUCTURE: This Cost/Value Methodology Statement updates prior guidance regarding the incorporation of evidence from published CEAs into clinical guidelines. It provides guidance for identifying and synthesizing relevant high-quality evidence, developing economic value statements, and communicating level of certainty in such statements. It defines the US cost-effectiveness threshold as $120,000 per quality-adjusted life year gained, highlights special considerations related to cardiovascular drugs and devices, emphasizes health equity considerations when interpreting CEAs, and defines a reference case for future CEAs.

  • Kazi, Dhruv S, Abdul R Abdullah, Suzanne Arnold V, Anirban Basu, Brandon K Bellows, Khadijah Breathett, Derek S Chew, et al. (2025) 2025. “2025 AHA/ACC Statement on Cost/Value Methodology in Clinical Practice Guidelines (Update From 2014 Statement): A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.”. Circulation. https://doi.org/10.1161/CIR.0000000000001377.
    Publisher's Version
    Publisher's Version

    AIM: The "2025 AHA/ACC Statement on Cost/Value Methodology in Clinical Practice Guidelines (Update From 2014 Statement)" describes a systematic approach for consistent implementation of "economic value statements" across ACC/AHA guidelines. It updates the cost-effectiveness threshold and proposes a new level of certainty framework that summarizes the strength of the available evidence. Additionally, it describes how cost-effectiveness analyses (CEAs) can help advance equity in population cardiovascular health.

    METHODS: A focused literature search was conducted from January 9, 2024, to February 2, 2024, encompassing English-language publications related to CEA methodology in PubMed, EMBASE, and the Cochrane Library, with publication dates ranging from 1973 to the present. Additional relevant studies published during the writing process (through June 25, 2024) were also considered by the writing committee.

    STRUCTURE: This Cost/Value Methodology Statement updates prior guidance regarding the incorporation of evidence from published CEAs into clinical guidelines. It provides guidance for identifying and synthesizing relevant high-quality evidence, developing economic value statements, and communicating level of certainty in such statements. It defines the US cost-effectiveness threshold as $120 000 per quality-adjusted life year gained, highlights special considerations related to cardiovascular drugs and devices, emphasizes health equity considerations when interpreting CEAs, and defines a reference case for future CEAs.

  • Penko, Joanne M, Brandon K Bellows, Susan Hennessy, Dhruv S Kazi, Ross Boylan, Yiyi Zhang, Pamela G Coxson, Lee Goldman, Kirsten Bibbins-Domingo, and Andrew E Moran. (2025) 2025. “Cost-Effectiveness of Hypertension Treatment According to 2017 American College of Cardiology and American Heart Association Guidelines.”. Circulation. Cardiovascular Quality and Outcomes 18 (8): e011872. https://doi.org/10.1161/CIRCOUTCOMES.124.011872.
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    BACKGROUND: Compared with the 2003 Seventh Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) guideline, the 2017 American College of Cardiology and American Heart Association guideline (ACC/AHA 2017) expanded hypertension diagnostic criteria to blood pressure (BP) ≥130/80 mm Hg and intensified treatment goals to <130/80 mm Hg. The cost-effectiveness of ACC/AHA 2017 guideline treatment has not been quantified.

    METHODS: We used the Cardiovascular Disease (CVD) Policy Model to simulate hypertension treatment according to ACC/AHA 2017 compared with JNC7 in untreated US adults aged 35 to 79 years. Outcomes were projected over 10 years and included CVD events and deaths, quality-adjusted life-years (QALYs), and total health care costs (ie, costs of antihypertensive treatment and costs of health care utilization for cardiovascular and noncardiovascular care, regardless of payer). Cost-effectiveness was calculated from a health care sector perspective as incremental health care costs divided by incremental QALYs.

    RESULTS: Under ACC/AHA 2017, 4.9 million more US adults are indicated for treatment and 14.9 million are recommended more intensive treatment goals compared with JNC7. Over 10 years, ACC/AHA 2017 versus JNC7 treatment would cost $48 300 per QALY gained ($38 300/QALY in men; $65 200/QALY in women). Overall, 34% of CVD events prevented by ACC/AHA 2017 versus JNC7 would be from expanded diagnosis (at $120 900/QALY gained), and 66% from intensified BP treatment goals (at $18 900/QALY gained). Cost-effectiveness improved with a longer time horizon ($17 600 per QALY gained at 30 years) and when generic drug costs were assumed in place of median US drug costs ($27 900 per QALY gained in 10 years). ACC/AHA 2017 is cost-saving in adults with BP ≥140/90 mm Hg and prior CVD or 10-year CVD risk ≥10%.

    CONCLUSIONS: Initiating hypertension treatment according to the ACC/AHA 2017 guideline in untreated US adults is cost-effective compared with JNC7 at 10 years. Prioritizing low-cost generic medicines and intensive BP treatment of high-CVD-risk adults with BP ≥140/90 mm Hg returns the most value.

  • Johnson, Neil, Joe Vandigo, Fernanda de Carvalho, Celina Gorre, Tanya Hall, Susan E Hennessy, Dhruv S Kazi, et al. (2025) 2025. “Experiences of People Diagnosed With High Levels of LDL Cholesterol and Atherosclerotic Cardiovascular Disease: Results from a Multinational Qualitative Study.”. Global Heart 20 (1): 63. https://doi.org/10.5334/gh.1441.
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    BACKGROUND: Elevated low-density lipoprotein cholesterol (LDL-C) levels are a leading risk factor for atherosclerotic cardiovascular disease (ASCVD), a major global cause of illness and death. Patients' qualitative insights about experiences, priorities, and needs are essential for creating more targeted, patient-centered quality improvement interventions.

    OBJECTIVES: To document the experiences of people with high levels of low-density LDL-C in three countries.

    METHODS: Qualitative study of 60-min in-depth interviews with 50 adult patients from Australia, Brazil, and the United States. The study was overseen by a Steering Committee comprising patients, patient advocates, researchers, and cardiologists. The interviews explored pathways and barriers to high LDL-C diagnosis; the burden of managing high LDL-C and the awareness of the association between high LDL-C and cardiovascular risks. The data were analyzed by applying a structured, team-based approach to coding qualitative data.

    RESULTS: There were three main pathways to diagnosing high cholesterol: routine physical exams conducted by primary care providers; symptomatic presentations or incidental findings during emergency visits and through a healthcare visit for another condition, frequently diabetes. Healthcare providers' communication styles influenced patients' perceptions of their conditions. Two-thirds of participants (n = 33) attempted lifestyle changes after their high cholesterol diagnosis, but work schedules and daily routines posed barriers to maintaining healthy habits. Some participants who experienced ASCVD events waited hours or days before seeking care, assuming their symptoms were not serious. After diagnosis of an ASCVD event, many patients feared death and worried about their families' futures. When asked about potential improvements to their current therapy, 21 patients mentioned reduced administration frequency.

    CONCLUSIONS: This pilot study provides insights into patients' experiences living with and managing elevated LDL-C. It describes opportunities for policymakers and healthcare providers to improve the detection of elevated LDL-C and support patients in understanding risks and strategies for reducing the risk of ASCVD events.

  • Chiang, Cho-Han, Yu-Cheng Chang, Chun-Chiao Yu, Xin Ya See, Tsu Hsien Wang, Nutchapon Xanthavanij, Junmin Song, et al. (2025) 2025. “Glucagon-Like Peptide 1 Receptor Agonists and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.”. Journal of Thrombosis and Haemostasis : JTH. https://doi.org/10.1016/j.jtha.2025.06.020.
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    BACKGROUND: Obesity is an established risk factor for venous thromboembolism (VTE). Observational data suggest that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce the risk of VTE. However, the effects of GLP-1RAs on VTE have not been tested in randomized controlled trials (RCTs).

    OBJECTIVES: To investigate the impact of GLP-1RAs on VTE risk using data from RCTs.

    METHODS: We conducted a systematic review and meta-analysis of placebo-controlled RCTs focusing on GLP-1RA use in patients with type 2 diabetes mellitus (T2DM) or obesity. Five databases were searched from inception to October 2024. The primary outcome was VTE, which was a composite of pulmonary embolism (PE), deep vein thrombosis (DVT), and VTE at other sites, and the secondary outcomes were the individual events.

    RESULTS: Twenty-seven RCTs with 84,003 patients were analyzed. The median incidence of VTE was 1.1 and 2.5 per 1,000 patient-years in the GLP-1RA and placebo groups, respectively. There was no statistically significant difference in overall VTE risk between GLP-1RA and placebo groups (RR 0.70, 95% CI 0.46-1.07). However, GLP-1RAs were associated with a significantly lower risk of PE (RR 0.60, 95% CI 0.39-0.94). In contrast, there were no significant differences in the risk of DVT (RR 1.24, 95% CI 0.67-2.27) or VTE at other sites (RR 0.56, 95% CI 0.25-1.26).

    CONCLUSIONS: In this meta-analysis of randomized trials, GLP-1RAs were not associated with a significant reduction in overall VTE risk but were associated with a lower risk of PE among patients with T2DM or obesity.

  • King, Sara J, Tenzin Yeshi Wangdak Yuthok, Adrian M Bacong, Abha Khandelwal, Dhruv S Kazi, Michael E Mussolino, Sally S Wong, et al. (2025) 2025. “Heart Disease Mortality in the United States, 1970 to 2022.”. Journal of the American Heart Association, e038644. https://doi.org/10.1161/JAHA.124.038644.
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    BACKGROUND: Studying trends in mortality is essential to advance understanding of population health. Further evaluation of long-term heart disease mortality trends and subtypes in the United States is needed to guide public health and clinical interventions.

    METHODS: This study used the National Vital Statistics System Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research data for adults aged 25 years and older in the United States from 1970 to 2022. Outcomes included absolute number and age-adjusted mortality of total heart disease, ischemic heart disease, and other heart disease subtypes.

    RESULTS: From 1970 to 2022, overall age-adjusted heart disease mortality decreased by 66% from 1970 to 2022 (from 761 to 258 per 100 000). In 1970, 91% of all heart disease deaths were ischemic, declining to 53% of all heart disease deaths in 2022. From 1970 to 2022, age-adjusted mortality decreased by 89% for acute myocardial infarction (from 354 to 40 per 100 000) and 81% for all ischemic heart disease (from 693 to 135 per 100 00). In contrast, from 1970 to 2022 age-adjusted mortality for other heart disease subtypes increased by 81% (from 68 to 123 per 100 000), with the greatest increases in heart failure (146% increase), hypertensive heart disease (106% increase) and arrhythmias (450% increase).

    CONCLUSIONS: Heart disease mortality has decreased over the past 5 decades. There is an increasing burden of mortality from other heart conditions including heart failure, hypertensive heart disease, and arrhythmias. Further efforts must be undertaken to address the growing challenge of these other heart conditions.

  • Chung, Mabel, Zaid I Almarzooq, Archana Tale, Yang Song, Issa J Dahabreh, Dhruv S Kazi, Suzanne J Baron, and Robert W Yeh. (2025) 2025. “Days at Home After Transcatheter Mitral Valve Repair Versus Medical Therapy Alone in Heart Failure.”. Journal of the American Heart Association 14 (1): e038401. https://doi.org/10.1161/JAHA.124.038401.
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    BACKGROUND: Transcatheter edge-to-edge repair of the mitral valve (mTEER) reduced a hierarchical end point that included death and heart failure hospitalization in COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation Trial). However, the magnitude to which mTEER increases the number of days a patient spends at home (DAH) in the first few years after treatment, a patient-centered end point not captured routinely in clinical trials, has not been evaluated. We compared 1- and 2-year DAH among patients with functional mitral regurgitation and heart failure randomized to mTEER plus medical therapy versus medical therapy alone (control) by linking the COAPT trial to comprehensive health care claims data.

    METHODS AND RESULTS: We linked data from COAPT trial participants to Medicare fee-for-service claims. DAH was calculated as the number of days alive and spent outside a hospital, skilled nursing facility, inpatient rehabilitation, long-term acute care hospital, emergency department, or observation stay after randomization. Treatment groups were compared using quantile regression to calculate the area under the curve of cumulative distribution functions. We linked 271 patients (mTEER 136/302, control 135/312) for a 2-year follow-up. Mean±SD DAH at 1 year was 312.0±95.6 in mTEER and 298.1±107.5 in controls with similar area under the curve (difference 13.9 days [-10.5 to 38.3], P=0.26). DAH at 2 years was 577.2±235.6 in mTEER and 518.2±253.0 in control with a higher area under the curve in mTEER (difference 59.0 days [0.07 to 117.9], P=0.0497).

    CONCLUSIONS: In the COAPT trial linked to Medicare claims, patients randomized to mTEER spent a similar number of DAH at 1 year but more time at home at 2 years compared with medical therapy alone.

  • Kohli-Lynch, Ciaran N, Andrew E Moran, Dhruv S Kazi, Kirsten Bibbins-Domingo, Neil Jordan, Dustin French, Yiyi Zhang, Thomas J Wang, and Brandon K Bellows. (2025) 2025. “Cost-Effectiveness of a Polypill for Cardiovascular Disease Prevention in an Underserved Population.”. JAMA Cardiology 10 (3): 224-33. https://doi.org/10.1001/jamacardio.2024.4812.
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    IMPORTANCE: The Southern Community Cohort Study (SCCS) Polypill Trial showed that a cardiovascular polypill (a single pill containing a statin and 3 half-standard dose antihypertensive medications) effectively controls cardiovascular disease (CVD) risk factors in a majority Black race and low-income population. The cost-effectiveness of polypill treatment in this population has not been previously studied.

    OBJECTIVE: To determine the cost-effectiveness of the cardiovascular polypill.

    DESIGN, SETTING, AND PARTICIPANTS: A discrete-event simulation version of the well-established CVD policy model simulated clinical and economic outcomes of the SCCS Polypill Trial from a health care sector perspective. A time horizon of 10 years was adopted. Polypill treatment was priced at $463 per year in the base-case analysis. Model input data were derived from the National Health and Nutrition Examination Survey, Medical Expenditure Panel Survey, pooled longitudinal cohort studies, the SCCS Polypill Trial, and published literature. Two cohorts were analyzed: an SCCS Polypill Trial-representative cohort of 100 000 individuals and all trial-eligible non-Hispanic Black US adults. Study parameters and model inputs were varied extensively in 1-way and probabilistic sensitivity analysis.

    EXPOSURES: Polypill treatment or usual care.

    MAIN OUTCOME AND MEASURES: Primary outcomes were direct health care costs (US dollar 2023) and quality-adjusted life-years (QALYs), both discounted 3% annually, and the incremental cost per QALY gained.

    RESULTS: In the trial-representative cohort of 100 000 individuals (mean [SD] age, 56.9 [5.9] years; 61 807 female [61.8%]), polypill treatment was projected to yield a mean of 1190 (95% uncertainty interval, 287-2159) additional QALYs compared with usual care, at a cost of approximately $10 152 000. Hence, polypill treatment was estimated to cost $8560 per QALY gained compared with usual care and was high value (<$50 000 per QALY gained) in 99% of simulations. Polypill treatment was estimated to be high value when priced at $559 or less per year and cost saving when priced at $443 or less per year. In almost all sensitivity analyses, polypill treatment remained high value. In a secondary analysis of 3 602 427 trial-eligible non-Hispanic Black US adults (mean [SD] age, 55.4 [7.6] years; 2 006 597 female [55.7%]), polypill treatment was high value, with an estimated cost of $13 400 per QALY gained.

    CONCLUSIONS AND RELEVANCE: Results of this economic evaluation suggest that polypill treatment could be a high value intervention for a low-income, majority Black population with limited access to health care services. It could additionally reduce health disparities.

  • Martin, Seth S, Aaron W Aday, Norrina B Allen, Zaid I Almarzooq, Cheryl A M Anderson, Pankaj Arora, Christy L Avery, et al. (2025) 2025. “2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.”. Circulation 151 (8): e41-e660. https://doi.org/10.1161/CIR.0000000000001303.
    Publisher's Version
    Publisher's Version

    BACKGROUND: The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).

    METHODS: The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2025 AHA Statistical Update is the product of a full year's worth of effort in 2024 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. This year's edition includes a continued focus on health equity across several key domains and enhanced global data that reflect improved methods and incorporation of ≈3000 new data sources since last year's Statistical Update.

    RESULTS: Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.

    CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

  • Chiang, Cho Han, Junmin Song, Yu-Cheng Chang, Soravis Osataphan, Yu-Che Lee, Ko-Yun Chang, Kuan-Yu Chi, et al. (2025) 2025. “Glucagon-Like Peptide 1 Receptor Agonists and Venous Thromboembolism in Type 2 Diabetes: A Target Trial Emulation.”. Blood Advances. https://doi.org/10.1182/bloodadvances.2025015871.
    Publisher's Version
    Publisher's Version

    Glucagon-like peptide 1 receptor agonists (GLP1-RA) are anti-diabetes agents recently approved for weight loss. Obesity is an established risk factor for venous thromboembolism (VTE). Moreover, preclinical studies have shown that GLP1-RA may attenuate thromboxaneinduced platelet activation. Therefore, we hypothesized that GLP1-RA use may reduce the risk of VTE. We performed a target trial emulation using a population-based database of electronic health records to evaluate whether GLP1-RA use is associated with a reduction in VTE in patients with type 2 diabetes mellitus (T2DM) compared with dipeptidyl peptidas e-4 inhibitors (DPP4i). Patients who were newly initiated on GLP1-RA were propensity scorematched to patients who were newly initiated on DPP4i. We evaluated the primary outcome, composite VTE, identified using ICD-10 codes, within 12 months of the initiation of GLP1-RA or DPP4i. The study cohort comprised 540,258 patients with 270,129 individuals receiving either GLP1-RA or DPP4i. Over 12 months of follow-up, patients who received GLP1-RA had a lower incidence of VTE compared with patients who received DPP4i (6.1 vs. 7.6 events per 1000 patient-years, hazard ratio [HR], 0.78 [95% CI: 0.73-0.83]). This was similar for PE (2.9 vs. 3.8 events per 1000 patient-years, HR, 0.74 [95% CI: 0.68-0.82]) and DVT (3.9 vs. 4.7 events per 1000 patient-years, HR, 0.81 [95% CI: 0.75-0.88]). In this propensity scorematched, target trial emulation study, patients with T2DM who received a GLP1-RA had a lower risk of VTE at one year compared with patients who received DPP4i.