Publications

2015

Krishnamurthi, Rita, V, Gabrielle deVeber, Valery L Feigin, Suzanne Barker-Collo, Heather Fullerton, Mark T Mackay, Finbar O’Callahan, et al. (2015) 2015. “Stroke Prevalence, Mortality and Disability-Adjusted Life Years in Children and Youth Aged 0-19 Years: Data from the Global and Regional Burden of Stroke 2013.”. Neuroepidemiology 45 (3): 177-89. https://doi.org/10.1159/000441087.
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BACKGROUND: There is increasing recognition of stroke as an important contributor to childhood morbidity and mortality. Current estimates of global childhood stroke burden and its temporal trends are sparse. Accurate and up-to-date estimates of childhood stroke burden are important for planning research and the resulting evidence-based strategies for stroke prevention and management.

OBJECTIVES: To estimate the prevalence, mortality and disability-adjusted life years (DALYs) for ischemic stroke (IS), hemorrhagic stroke (HS) and all stroke types combined globally from 1990 to 2013.

METHODOLOGY: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease 2013 methods. All available data on stroke-related incidence, prevalence, excess mortality and deaths were collected. Statistical models and country-level covariates were employed to produce comprehensive and consistent estimates of prevalence and mortality. Stroke-specific disability weights were used to estimate years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013.

RESULTS: In 2013, there were 97,792 (95% UI 90,564-106,016) prevalent cases of childhood IS and 67,621 (95% UI 62,899-72,214) prevalent cases of childhood HS, reflecting an increase of approximately 35% in the absolute numbers of prevalent childhood strokes since 1990. There were 33,069 (95% UI 28,627-38,998) deaths and 2,615,118 (95% UI 2,265,801-3,090,822) DALYs due to childhood stroke in 2013 globally, reflecting an approximately 200% decrease in the absolute numbers of death and DALYs in childhood stroke since 1990. Between 1990 and 2013, there were significant increases in the global prevalence rates of childhood IS, as well as significant decreases in the global death rate and DALYs rate of all strokes in those of age 0-19 years. While prevalence rates for childhood IS and HS decreased significantly in developed countries, a decline was seen only in HS, with no change in prevalence rates of IS, in developing countries. The childhood stroke DALY rates in 2013 were 13.3 (95% UI 10.6-17.1) for IS and 92.7 (95% UI 80.5-109.7) for HS per 100,000. While the prevalence of childhood IS compared to childhood HS was similar globally, the death rate and DALY rate of HS was 6- to 7-fold higher than that of IS. In 2013, the prevalence rate of both childhood IS and HS was significantly higher in developed countries than in developing countries. Conversely, both death and DALY rates for all stroke types were significantly lower in developed countries than in developing countries in 2013. Men showed a trend toward higher childhood stroke death rates (1.5 (1.3-1.8) per 100,000) than women (1.1 (0.9-1.5) per 100,000) and higher childhood stroke DALY rates (120.1 (100.8-143.4) per 100,000) than women (90.9 (74.6-122.4) per 100,000) globally in 2013.

CONCLUSIONS: Globally, between 1990 and 2013, there was a significant increase in the absolute number of prevalent childhood strokes, while absolute numbers and rates of both deaths and DALYs declined significantly. The gap in childhood stroke burden between developed and developing countries is closing; however, in 2013, childhood stroke burden in terms of absolute numbers of prevalent strokes, deaths and DALYs remained much higher in developing countries. There is an urgent need to address these disparities with both global and country-level initiatives targeting prevention as well as improved access to acute and chronic stroke care.

Barker-Collo, Suzanne, Derrick A Bennett, Rita Krishnamurthi V, Priya Parmar, Valery L Feigin, Mohsen Naghavi, Mohammed H Forouzanfar, et al. (2015) 2015. “Sex Differences in Stroke Incidence, Prevalence, Mortality and Disability-Adjusted Life Years: Results from the Global Burden of Disease Study 2013.”. Neuroepidemiology 45 (3): 203-14. https://doi.org/10.1159/000441103.
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BACKGROUND: Accurate information on stroke burden in men and women are important for evidence-based healthcare planning and resource allocation. Previously, limited research suggested that the absolute number of deaths from stroke in women was greater than in men, but the incidence and mortality rates were greater in men. However, sex differences in various metrics of stroke burden on a global scale have not been a subject of comprehensive and comparable assessment for most regions of the world, nor have sex differences in stroke burden been examined for trends over time.

METHODS: Stroke incidence, prevalence, mortality, disability-adjusted life years (DALYs) and healthy years lost due to disability were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Data inputs included all available information on stroke incidence, prevalence and death and case fatality rates. Analysis was performed separately by sex and 5-year age categories for 188 countries. Statistical models were employed to produce globally comprehensive results over time. All rates were age-standardized to a global population and 95% uncertainty intervals (UIs) were computed.

FINDINGS: In 2013, global ischemic stroke (IS) and hemorrhagic stroke (HS) incidence (per 100,000) in men (IS 132.77 (95% UI 125.34-142.77); HS 64.89 (95% UI 59.82-68.85)) exceeded those of women (IS 98.85 (95% UI 92.11-106.62); HS 45.48 (95% UI 42.43-48.53)). IS incidence rates were lower in 2013 compared with 1990 rates for both sexes (1990 male IS incidence 147.40 (95% UI 137.87-157.66); 1990 female IS incidence 113.31 (95% UI 103.52-123.40)), but the only significant change in IS incidence was among women. Changes in global HS incidence were not statistically significant for males (1990 = 65.31 (95% UI 61.63-69.0), 2013 = 64.89 (95% UI 59.82-68.85)), but was significant for females (1990 = 64.892 (95% UI 59.82-68.85), 2013 = 45.48 (95% UI 42.427-48.53)). The number of DALYs related to IS rose from 1990 (male = 16.62 (95% UI 13.27-19.62), female = 17.53 (95% UI 14.08-20.33)) to 2013 (male = 25.22 (95% UI 20.57-29.13), female = 22.21 (95% UI 17.71-25.50)). The number of DALYs associated with HS also rose steadily and was higher than DALYs for IS at each time point (male 1990 = 29.91 (95% UI 25.66-34.54), male 2013 = 37.27 (95% UI 32.29-45.12); female 1990 = 26.05 (95% UI 21.70-30.90), female 2013 = 28.18 (95% UI 23.68-33.80)).

INTERPRETATION: Globally, men continue to have a higher incidence of IS than women while significant sex differences in the incidence of HS were not observed. The total health loss due to stroke as measured by DALYs was similar for men and women for both stroke subtypes in 2013, with HS higher than IS. Both IS and HS DALYs show an increasing trend for both men and women since 1990, which is statistically significant only for IS among men. Ongoing monitoring of sex differences in the burden of stroke will be needed to determine if disease rates among men and women continue to diverge. Sex disparities related to stroke will have important clinical and policy implications that can guide funding and resource allocation for national, regional and global health programs.

Feigin, Valery L, George A Mensah, Bo Norrving, Christopher J L Murray, Gregory A Roth, and GBD 2013 Stroke Panel Experts Group. (2015) 2015. “Atlas of the Global Burden of Stroke (1990-2013): The GBD 2013 Study.”. Neuroepidemiology 45 (3): 230-6. https://doi.org/10.1159/000441106.
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BACKGROUND: World mapping is an important tool to visualize stroke burden and its trends in various regions and countries.

OBJECTIVES: To show geographic patterns of incidence, prevalence, mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs) and their trends for ischemic stroke and hemorrhagic stroke in the world for 1990-2013.

METHODOLOGY: Stroke incidence, prevalence, mortality, DALYs and YLDs were estimated following the general approach of the Global Burden of Disease (GBD) 2010 with several important improvements in methods. Data were updated for mortality (through April 2014) and stroke incidence, prevalence, case fatality and severity through 2013. Death was estimated using an ensemble modeling approach. A new software package, DisMod-MR 2.0, was used as part of a custom modeling process to estimate YLDs. All rates were age-standardized to new GBD estimates of global population. All estimates have been computed with 95% uncertainty intervals.

RESULTS: Age-standardized incidence, mortality, prevalence and DALYs/YLDs declined over the period from 1990 to 2013. However, the absolute number of people affected by stroke has substantially increased across all countries in the world over the same time period, suggesting that the global stroke burden continues to increase. There were significant geographical (country and regional) differences in stroke burden in the world, with the majority of the burden borne by low- and middle-income countries.

CONCLUSIONS: Global burden of stroke has continued to increase in spite of dramatic declines in age-standardized incidence, prevalence, mortality rates and disability. Population growth and aging have played an important role in the observed increase in stroke burden.

Krishnamurthi, Rita, V, Andrew E Moran, Valery L Feigin, Suzanne Barker-Collo, Bo Norrving, George A Mensah, Steve Taylor, et al. (2015) 2015. “Stroke Prevalence, Mortality and Disability-Adjusted Life Years in Adults Aged 20-64 Years in 1990-2013: Data from the Global Burden of Disease 2013 Study.”. Neuroepidemiology 45 (3): 190-202. https://doi.org/10.1159/000441098.
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Publisher's Version

BACKGROUND: Recent evidence suggests that stroke is increasing as a cause of morbidity and mortality in younger adults, where it carries particular significance for working individuals. Accurate and up-to-date estimates of stroke burden are important for planning stroke prevention and management in younger adults.

OBJECTIVES: This study aims to estimate prevalence, mortality and disability-adjusted life years (DALYs) and their trends for total, ischemic stroke (IS) and hemorrhagic stroke (HS) in the world for 1990-2013 in adults aged 20-64 years.

METHODOLOGY: Stroke prevalence, mortality and DALYs were estimated using the Global Burden of Disease (GBD) 2013 methods. All available data on rates of stroke incidence, excess mortality, prevalence and death were collected. Statistical models were used along with country-level covariates to estimate country-specific stroke burden. Stroke-specific disability weights were used to compute years lived with disability and DALYs. Means and 95% uncertainty intervals (UIs) were calculated for prevalence, mortality and DALYs. The median of the percent change and 95% UI were determined for the period from 1990 to 2013.

RESULTS: In 2013, in younger adults aged 20-64 years, the global prevalence of HS was 3,725,085 cases (95% UI 3,548,098-3,871,018) and IS was 7,258,216 cases (95% UI 6,996,272-7,569,403). Globally, between 1990 and 2013, there were significant increases in absolute numbers and prevalence rates of both HS and IS for younger adults. There were 1,483,707 (95% UI 1,340,579-1,658,929) stroke deaths globally among younger adults but the number of deaths from HS (1,047,735 (95% UI 945,087-1,184,192)) was significantly higher than the number of deaths from IS (435,972 (95% UI 354,018-504,656)). There was a 20.1% (95% UI -23.6 to -10.3) decline in the number of total stroke deaths among younger adults in developed countries but a 36.7% (95% UI 26.3-48.5) increase in developing countries. Death rates for all strokes among younger adults declined significantly in developing countries from 47 (95% UI 42.6-51.7) in 1990 to 39 (95% UI 35.0-43.8) in 2013. Death rates for all strokes among younger adults also declined significantly in developed countries from 33.3 (95% UI 29.8-37.0) in 1990 to 23.5 (95% UI 21.1-26.9) in 2013. A significant decrease in HS death rates for younger adults was seen only in developed countries between 1990 and 2013 (19.8 (95% UI 16.9-22.6) and 13.7 (95% UI 12.1-15.9)) per 100,000). No significant change was detected in IS death rates among younger adults. The total DALYs from all strokes in those aged 20-64 years was 51,429,440 (95% UI 46,561,382-57,320,085). Globally, there was a 24.4% (95% UI 16.6-33.8) increase in total DALY numbers for this age group, with a 20% (95% UI 11.7-31.1) and 37.3% (95% UI 23.4-52.2) increase in HS and IS numbers, respectively.

CONCLUSIONS: Between 1990 and 2013, there were significant increases in prevalent cases, total deaths and DALYs due to HS and IS in younger adults aged 20-64 years. Death and DALY rates declined in both developed and developing countries but a significant increase in absolute numbers of stroke deaths among younger adults was detected in developing countries. Most of the burden of stroke was in developing countries. In 2013, the greatest burden of stroke among younger adults was due to HS. While the trends in declining death and DALY rates in developing countries are encouraging, these regions still fall far behind those of developed regions of the world. A more aggressive approach toward primary prevention and increased access to adequate healthcare services for stroke is required to substantially narrow these disparities.

Collaborators, GBD 2013 Risk Factors, Mohammad H Forouzanfar, Lily Alexander, Ross Anderson, Victoria F Bachman, Stan Biryukov, Michael Brauer, et al. (2015) 2015. “Global, Regional, and National Comparative Risk Assessment of 79 Behavioural, Environmental and Occupational, and Metabolic Risks or Clusters of Risks in 188 Countries, 1990-2013: A Systematic Analysis for the Global Burden of Disease Study 2013.”. Lancet (London, England) 386 (10010): 2287-323. https://doi.org/10.1016/S0140-6736(15)00128-2.
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BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution.

METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol.

FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa.

INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks.

FUNDING: Bill & Melinda Gates Foundation.

2014

Solomon, Matthew D, Alan S Go, David Shilane, Derek B Boothroyd, Thomas K Leong, Dhruv S Kazi, Tara I Chang, and Mark A Hlatky. (2014) 2014. “Comparative Effectiveness of Clopidogrel in Medically Managed Patients With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction.”. Journal of the American College of Cardiology 63 (21): 2249-57. https://doi.org/10.1016/j.jacc.2014.02.586.
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OBJECTIVES: This study sought to examine the effectiveness of clopidogrel in real-world, medically managed patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI).

BACKGROUND: Although clinical trials have demonstrated the efficacy of clopidogrel to reduce cardiovascular (CV) morbidity and mortality in medically managed patients with UA or NSTEMI, the effectiveness of clopidogrel in actual clinical practice is less certain.

METHODS: A retrospective cohort study was conducted of Kaiser Permanente Northern California members without known coronary artery disease or prior clopidogrel use who presented with UA or NSTEMI between 2003 and 2008 and were medically managed (i.e., no percutaneous coronary intervention or coronary artery bypass grafting during the index hospitalization or within 7 days post-discharge). Over 2 years of follow-up, we measured the association between clopidogrel use and all-cause mortality, hospital stay for MI, and a composite endpoint of death or MI using propensity-matched multivariable Cox analyses.

RESULTS: We identified 16,365 patients with incident UA (35%) or NSTEMI (65%); 36% of these patients were prescribed clopidogrel within 7 days of discharge. In 8,562 propensity score-matched patients, clopidogrel users had lower rates of all-cause mortality (8.3% vs. 13.0%; p < 0.01; adjusted hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.54 to 0.72) and the composite of death or MI (13.5% vs. 17.4%; p < 0.01; HR: 0.74, CI: 0.66 to 0.84), but not MI alone (6.7% vs. 7.2%; p = 0.30; HR: 0.93, CI: 0.78 to 1.11), compared with nonusers of clopidogrel. The association between clopidogrel use and the composite of death or MI was significant only among patients presenting with NSTEMI (HR: 0.67; CI: 0.59 to 0.76; pint < 0.01), not among those presenting with UA (HR: 1.25; CI: 0.94 to 1.67).

CONCLUSIONS: In a large, community-based cohort of patients who were medically managed after UA/NSTEMI, clopidogrel use was associated with a lower risk of death and MI, particularly among patients with NSTEMI.

Kazi, Dhruv S, Alan M Garber, Rashmee U Shah, Adams Dudley, Matthew W Mell, Ceron Rhee, Solomon Moshkevich, Derek B Boothroyd, Douglas K Owens, and Mark A Hlatky. (2014) 2014. “Cost-Effectiveness of Genotype-Guided and Dual Antiplatelet Therapies in Acute Coronary Syndrome.”. Annals of Internal Medicine 160 (4): 221-32.
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BACKGROUND: The choice of antiplatelet therapy after acute coronary syndrome (ACS) is complicated: Ticagrelor and prasugrel are novel alternatives to clopidogrel, patients with some genotypes may not respond to clopidogrel, and low-cost generic formulations of clopidogrel are available.

OBJECTIVE: To determine the most cost-effective strategy for dual antiplatelet therapy after percutaneous coronary intervention for ACS.

DESIGN: Decision-analytic model.

DATA SOURCES: Published literature, Medicare claims, and life tables.

TARGET POPULATION: Patients having percutaneous coronary intervention for ACS.

TIME HORIZON: Lifetime.

PERSPECTIVE: Societal.

INTERVENTION: Five strategies were examined: generic clopidogrel, prasugrel, ticagrelor, and genotyping for polymorphisms of CYP2C19 with carriers of loss-of-function alleles receiving either ticagrelor (genotyping with ticagrelor) or prasugrel (genotyping with prasugrel) and noncarriers receiving clopidogrel.

OUTCOME MEASURES: Direct medical costs, quality-adjusted life years(QALYs), and incremental cost-effectiveness ratios (ICERs).

RESULTS OF BASE-CASE ANALYSIS: The clopidogrel strategy produced$179 301 in costs and 9.428 QALYs. Genotyping with prasugrel was superior to prasugrel alone, with an ICER of $35 800 per QALY relative to clopidogrel. Genotyping with ticagrelor was more effective than genotyping with prasugrel ($30 200 per QALY relative to clopidogrel). Ticagrelor was the most effective strategy($52 600 per QALY relative to genotyping with ticagrelor).

RESULTS OF SENSITIVITY ANALYSIS: Stronger associations between genotype and thrombotic outcomes rendered ticagrelor substantially less cost-effective ($104 800 per QALY). Genotyping with prasugrel was the preferred therapy among patients who could not tolerate ticagrelor.

LIMITATION: No randomized trials have directly compared genotyping strategies or prasugrel with ticagrelor.

CONCLUSION: Genotype-guided personalization may improve the cost-effectiveness of prasugrel and ticagrelor after percutaneous coronary intervention for ACS, but ticagrelor for all patients may bean economically reasonable alternative in some settings.

Andersson, Charlotte, David Shilane, Alan S Go, Tara I Chang, Dhruv Kazi, Matthew D Solomon, Derek B Boothroyd, and Mark A Hlatky. (2014) 2014. “β-Blocker Therapy and Cardiac Events Among Patients With Newly Diagnosed Coronary Heart Disease.”. Journal of the American College of Cardiology 64 (3): 247-52. https://doi.org/10.1016/j.jacc.2014.04.042.
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BACKGROUND: The effectiveness of beta-blockers for preventing cardiac events has been questioned for patients who have coronary heart disease (CHD) without a prior myocardial infarction (MI).

OBJECTIVES: The purpose of this study was to assess the association of beta-blockers with outcomes among patients with new-onset CHD.

METHODS: We studied consecutive patients discharged after the first CHD event (acute coronary syndrome or coronary revascularization) between 2000 and 2008 in an integrated healthcare delivery system who did not use beta-blockers in the year before entry. We used time-varying Cox regression models to determine the hazard ratio (HR) associated with beta-blocker treatment and used treatment-by-covariate interaction tests (p(int)) to determine whether the association differed for patients with or without a recent MI.

RESULTS: A total of 26,793 patients were included, 19,843 of whom initiated beta-blocker treatment within 7 days of discharge from their initial CHD event. Over an average of 3.7 years of follow-up, 6,968 patients had an MI or died. Use of beta-blockers was associated with an adjusted HR for mortality of 0.90 (95% confidence limits [CL]: 0.84 to 0.96), and an adjusted HR for death or MI of 0.92 (CL: 0.87 to 0.97). The association between beta-blockers and outcomes differed significantly between patients with and without a recent MI (HR for death: 0.85 vs. 1.02, p(int) = 0.007; and HR for death or MI: 0.87 vs. 1.03, p(int) = 0.005).

CONCLUSIONS: Use of beta-blockers among patients with new-onset CHD was associated with a lower risk of cardiac events only among patients with a recent MI.

  • 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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    Publisher's Version

    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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    Publisher's Version

    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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    Publisher's Version

    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.
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    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.
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    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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    Publisher's Version

    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.