JCL Roundtable. Making prevention a priority.

Clinical lipidology belongs par excellence to the preventive mode of medical practice. This Roundtable brings two long-time advocates of cardiometabolic prevention and a newly minted preventive cardiologist into a discussion that expands their recent JCL editorial on this topic. Atherosclerosis is a single disease process that leads to approximately 25% of deaths in economically advanced nations and a growing fraction of mortality and morbidity in nations with developing and emerging economies. Our discussants suggest that at least 75% of atherosclerotic cardiovascular disease can be prevented. Diet and lifestyle including physical activity are the cornerstones for this effort. Public and private choices about diet-lifestyle are influenced by economics, education (especially in childhood), inequities, technology, misinformation, and trust. Lipid clinics perform well with pharmacologic treatment of lipid disorders and increasingly give attention to hypertension, obesity, and diabetes as needed. Cardiometabolic prevention in the clinic works best through provider teams. Business considerations and exemplary programs are highlighted.

Can Cost-effectiveness Analysis Inform Genotype-Guided Aspirin Use for Primary Colorectal Cancer Prevention?

BACKGROUND: Inherited genetic variants can modify the cancer-chemopreventive effect of aspirin. We evaluated the clinical and economic value of genotype-guided aspirin use for colorectal cancer chemoprevention in average-risk individuals. METHODS: A decision analytical model compared genotype-guided aspirin use versus no genetic testing, no aspirin. The model simulated 100,000 adults ≥50 years of age with average colorectal cancer and cardiovascular disease risk. Low-dose aspirin daily starting at age 50 years was recommended only for those with a genetic test result indicating a greater reduction in colorectal cancer risk with aspirin use. The primary outcomes were quality-adjusted life-years (QALY), costs, and incremental cost-effectiveness ratio (ICER). RESULTS: The mean cost of using genotype-guided aspirin was $187,109 with 19.922 mean QALYs compared with $186,464 with 19.912 QALYs for no genetic testing, no aspirin. Genotype-guided aspirin yielded an ICER of $66,243 per QALY gained, and was cost-effective in 58% of simulations at the $100,000 willingness-to-pay threshold. Genotype-guided aspirin was associated with 1,461 fewer polyps developed, 510 fewer colorectal cancer cases, and 181 fewer colorectal cancer-related deaths. This strategy prevented 1,078 myocardial infarctions with 1,430 gastrointestinal bleeding events, and 323 intracranial hemorrhage cases compared with no genetic testing, no aspirin. CONCLUSIONS: Genotype-guided aspirin use for colorectal cancer chemoprevention may offer a cost-effective approach for the future management of average-risk individuals. IMPACT: A genotype-guided aspirin strategy may prevent colorectal cancer, colorectal cancer-related deaths, and myocardial infarctions, while minimizing bleeding adverse events. This model establishes a framework for genetically-guided aspirin use for targeted chemoprevention of colorectal cancer with application toward commercial testing in this population.

Long-term Impacts and Benefit-Cost Analysis of the Communities That Care Prevention System at Age 23, 12 Years After Baseline.

This study estimated sustained impacts and long-term benefits and costs of the Communities That Care (CTC) prevention system, implemented and evaluated in a longitudinal cluster-randomized trial involving 24 communities in seven states. Analyses utilized reports from a longitudinal panel of 4407 participants, followed since the study's baseline in grade 5, with most recent follow-up 12 years later at age 23. Impacts on lifetime abstinence from primary outcomes of substance use and antisocial behavior were estimated using generalized linear mixed Poisson regression analysis, adjusted for individual and community-level covariates. Possible cascading effects on 4-year college completion, major depressive disorder, and generalized anxiety disorder through age 23 were evaluated as secondary outcomes. CTC had a statistically significant global effect on primary outcomes and also on combined primary and secondary outcomes. Among primary outcomes, point estimates suggested absolute improvements in lifetime abstinence of 3.5 to 6.1% in the intervention arm and relative improvements of 13 to 55%; 95% confidence intervals revealed some uncertainty in estimates. Among secondary outcomes, 4-year college completion was 1.9% greater among young adults from intervention communities, a 20% relative improvement. Mental health outcomes were approximately the same across trial arms. Although CTC had small sustained effects through age 23, benefit-cost analyses indicated CTC was reliably cost beneficial, with a net present value of $7152 (95% credible interval: $1253 to $15,268) per participant from primary impacts and $17,919 ($306 to $39,186) when secondary impacts were also included. It remained cost beneficial even when impacts were adjusted downward due to the involvement of CTC's developer in the trial. Findings suggest that broader dissemination of CTC could improve public health and individual lives in the long term and generate positive net benefits to society.

Cost-effectiveness of statins for primary prevention of atherosclerotic cardiovascular disease among people living with HIV in the United States.

BACKGROUND: Expanding statin use may help to alleviate the excess burden of atherosclerotic cardiovascular disease in people living with HIV (PLHIV). Pravastatin and pitavastatin are preferred agents due to their lack of substantial interaction with antiretroviral therapy. We aimed to evaluate the cost-effectiveness of pravastatin and pitavastatin for the primary prevention of atherosclerotic cardiovascular disease among PLHIV in the United States. METHODS: We developed a microsimulation model that randomly selected (with replacement) individuals from the Data-collection on Adverse Effects of Anti-HIV Drugs study with follow-up between 2013 and 2016. Our study population was PLHIV aged 40 to 75 years, stable on antiretroviral therapy, and not currently using lipid-lowering therapy. Direct medical costs and quality-adjusted life-years (QALYs) were assigned in annual cycles and discounted at 3% per year. We assumed a willingness-to-pay threshold of $100,000/QALY gained. The interventions assessed were as follows: (1) treating no one with statins; (2) treating everyone with generic pravastatin 40 mg/day (drug cost $236/year) and (3) treating everyone with branded pitavastatin 4 mg/day (drug cost $2,828/year). The model simulated each individual's probability of experiencing atherosclerotic cardiovascular disease over 20 years. RESULTS: Persons receiving pravastatin accrued 0.024 additional QALYs compared with those not receiving a statin, at an incremental cost of $1338, giving an incremental cost-effectiveness ratio of $56,000/QALY gained. Individuals receiving pitavastatin accumulated 0.013 additional QALYs compared with those using pravastatin, at an additional cost of $18,251, giving an incremental cost-effectiveness ratio of $1,444,000/QALY gained. These findings were most sensitive to the pill burden associated with daily statin administration, statin costs, statin efficacy and baseline atherosclerotic cardiovascular disease risk. In probabilistic sensitivity analysis, no statin was optimal in 5.2% of simulations, pravastatin was optimal in 94.8% of simulations and pitavastatin was never optimal. CONCLUSIONS: Pravastatin was projected to be cost-effective compared with no statin. With substantial price reduction, pitavastatin may be cost-effective compared with pravastatin. These findings bode well for the expanded use of statins among PLHIV in the United States. To gain greater confidence in our conclusions it is important to generate strong, HIV-specific estimates on the efficacy of statins and the quality-of-life burden associated with taking an additional daily pill.

Targeting of the diabetes prevention program leads to substantial benefits when capacity is constrained.

OBJECTIVE: Approximately 84 million people in the USA have pre-diabetes, but only a fraction of them receive proven effective therapies to prevent type 2 diabetes. We estimated the value of prioritizing individuals at highest risk of progression to diabetes for treatment, compared to non-targeted treatment of individuals meeting inclusion criteria for the Diabetes Prevention Program (DPP). METHODS: Using microsimulation to project outcomes in the DPP trial population, we compared two interventions to usual care: (1) lifestyle modification and (2) metformin administration. For each intervention, we compared targeted and non-targeted strategies, assuming either limited or unlimited program capacity. We modeled the individualized risk of developing diabetes and projected diabetic outcomes to yield lifetime costs and quality-adjusted life expectancy, from which we estimated net monetary benefits (NMB) for both lifestyle and metformin versus usual care. RESULTS: Compared to usual care, lifestyle modification conferred positive benefits and reduced lifetime costs for all eligible individuals. Metformin's NMB was negative for the lowest population risk quintile. By avoiding use when costs outweighed benefits, targeted administration of metformin conferred a benefit of $500 per person. If only 20% of the population could receive treatment, when prioritizing individuals based on diabetes risk, rather than treating a 20% random sample, the difference in NMB ranged from $14,000 to $20,000 per person. CONCLUSIONS: Targeting active diabetes prevention to patients at highest risk could improve health outcomes and reduce costs compared to providing the same intervention to a similar number of patients with pre-diabetes without targeted selection.

Icosapent Ethyl for Primary Versus Secondary Prevention of Major Adverse Cardiovascular Events in Hypertriglyceridemia: Value for Money Analysis.

BACKGROUND: Icosapent ethyl (IPE) is approved for the prevention of major adverse cardiovascular events (MACE) in patients with hypertriglyceridemia. However, due to budget constraints, access to IPE will inevitably be limited to a fraction of eligible patients. To help maximize value for money spent, we estimated the number of preventable MACE when providing IPE for primary versus secondary prevention. METHODS: The number of preventable MACE was estimated by dividing the available budget by the cost needed to treat (CNT) to prevent one MACE. CNT was calculated as the product of the number needed to treat (NNT) to prevent 1 MACE by therapy cost. NNT values were determined according to the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) results. The budget limit was set as the United States' threshold suggested by the Institute for Clinical and Economic Review. Sensitivity analysis was performed regarding the cost of IPE in the United States. RESULTS: The NNT to prevent 1 MACE over 4.9 years in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial primary prevention cohort was 59 (95% confidence interval [CI]: 24-∞) versus 14 (11-21) for secondary prevention. At an annual IPE cost of $2915, the CNT to prevent 1 MACE was $842,726 (95% CI: $342,804-∞) and $199,969 ($157,118-$299,953) accordingly. A total of $819 million worth of IPE can avoid 4762 MACE (95% CI: 0-11,707) versus 20,069 (13,379-25,541), when provided as primary versus secondary prevention therapy; P < .001. The number of avoided MACE is sensitive to IPE price. CONCLUSIONS: Prioritizing IPE therapy for patients with an established cardiovascular disease may provide significantly more value for money than primary prevention.

Cost-effectiveness of the Da Qing diabetes prevention program: A modelling study.

OBJECTIVE: The Da Qing Diabetes Prevention program (DQDP) was a randomized lifestyle modification intervention conducted in 1986 for the prevention and control of type 2 diabetes in individuals with impaired glucose tolerance. The current study estimated long-term cost-effectiveness of the program based on the health utilities from the Chinese population. METHODS: A Markov Monte Carlo model was developed to estimate the impact of the intervention from the healthcare system perspective. The analysis was run over 30-year and lifetime periods and costs were estimated respectively as health management service costs. Baseline characteristics and intervention effects were assessed from the DQDP. Utilities and costs were generated from relevant literature. The outcome measures were program cost per quality-adjusted life-years (QALYs) gained and incremental cost-effectiveness ratio (ICER) of the intervention. Sensitivity analyses and threshold analyses were performed. RESULTS: Using a 30-year horizon, the intervention strategy was cost-saving and was associated with better health outcomes (increase of 0.74 QALYs per intervention participant). Using a lifetime horizon, the intervention strategy was cost-saving and was associated with additional 1.44 QALYs. Sensitivity analyses showed that the overall ICER was most strongly influenced by the hazard ratio of cardiovascular disease event. CONCLUSIONS: The Da Qing lifestyle intervention in a Chinese population with impaired glucose tolerance is likely to translate into substantial economic value. It is cost-saving over a 30-year time and lifetime frame.

Excess Medical Care Spending: The Categories, Magnitude, and Opportunity Costs of Wasteful Spending in the United States.

Landmark reports from reputable sources have concluded that the United States wastes hundreds of billions of dollars every year on medical care that does not improve health outcomes. While there is widespread agreement over how wasteful medical care spending is defined, there is no consensus on its magnitude or categories. A shared understanding of the magnitude and components of the issue may aid in systematically reducing wasteful spending and creating opportunities for these funds to improve public health.To this end, we performed a review and crosswalk analysis of the literature to retrieve comprehensive estimates of wasteful medical care spending. We abstracted each source's definitions, categories of waste, and associated dollar amounts. We synthesized and reclassified waste into 6 categories: clinical inefficiencies, missed prevention opportunities, overuse, administrative waste, excessive prices, and fraud and abuse.Aggregate estimates of waste varied from $600 billion to more than $1.9 trillion per year, or roughly $1800 to $5700 per person per year. Wider recognition by public health stakeholders of the human and economic costs of medical waste has the potential to catalyze health system transformation.

Impact of China's Low Centralized Medicine Procurement Prices on the Cost-Effectiveness of Statins for the Primary Prevention of Atherosclerotic Cardiovascular Disease.

Background: Statin medications reduce the risk of atherosclerotic cardiovascular disease (ASCVD). China's new central government medicine procurement policy lowered statin prices by five-fold or more, which may impact the cost-effectiveness of statin therapy. Objective: To explore the impact of China's 2019 centralized medicine procurement policy on the cost-effectiveness of statins treatment for primary ASCVD prevention. Methods: A microsimulation decision tree analytic model was built using individual participant data from ASCVD-free adults aged 35-64 years (n = 21,265) in the China Multi-provincial Cohort Study. ASCVD incidence, costs (2019 Int$), and quality-adjusted life years (QALYs) over a 10-year period from health-care sector and societal perspectives were estimated. Effect and cost-effectiveness of low-dose statins (equivalent potency regimens of simvastatin 20 mg/day, atorvastatin 10 mg/day, or rosuvastatin 5 mg/day) and moderate-dose (double low dose) statins therapy were simulated. The incremental cost-effectiveness ratio (ICER) of statin treatment was compared with no treatment by category of 10-year ASCVD risk. New lower prices of statins were from the centralized procurement policy bid-winning announcement file. One-way and probabilistic sensitivity analyses quantified model uncertainty. Results: Low-dose statins interventions reduced 10-year ASCVD incidence by 4.1%, 9.7%, and 15.5% among people with low, moderate, and high risk comparing to no treatment. Lowering statin prices to the 2019 central government procurement policy level could lower the ICER of low-dose statins treatment for high-risk people from Int$ 141,000 to Int$ 51,300 per QALY gained from health-care sector perspective. Moderate-dose statin treatment lowered the ICER compared with the low-dose statins treatment in each ASCVD risk category (Int$ 43,100 vs. Int$ 51,300 per QALY gained from the health-care sector perspective for high risk people). Cost-effectiveness improved progressively with increased baseline ASCVD risk. Conclusion: Implementing low central government prices will substantially improve the cost-effectiveness of statins for primary ASCVD prevention in 35-64-year-old Chinese adults.

Systematic Review of Economic Evaluations of Primary Caries Prevention in 2- to 5-Year-Old Preschool Children.

OBJECTIVES: To describe and summarize evidence on economic evaluations (EEs) of primary caries prevention in preschool children aged 2 to 5 years and to evaluate the reporting quality of full EE studies using a quality assessment tool. METHODS: A systematic literature search was conducted in several databases. Full and partial EEs were included. The reporting quality of full EE studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: A total of 808 studies were identified, and 39 were included in the review. Most papers were published between 2000 and 2017 and originated in the United States and the United Kingdom. The most common type of intervention investigated was a complex multicomponent intervention, followed by water fluoridation. Cost analysis and cost-effectiveness analysis were the most frequently used types of EE. One study employed cost-utility analysis. The proportion of full EEs increased over time. The parameters not reported well included study perspective, baseline year, sensitivity analysis, and discount rate. The CHEERS items that were most often unmet were characterizing uncertainty, study perspective, study parameters, and estimating resources and costs. CONCLUSIONS: Within the past 2 decades, there has been an increase in the number of EEs of caries prevention interventions in preschool children. There was inconsistency in how EEs were conducted and reported. Lack of preference-based health-related quality-of-life measure utilization in the field was identified. The use of appropriate study methodologies and greater attention to recommended EE design are required to further improve quality.

Differential Association of HIV Funding With HIV Mortality by Race/Ethnicity, United States, 1999-2017.

OBJECTIVE: Federal funds have been spent to reduce the disproportionate effects of HIV/AIDS on racial/ethnic minority groups in the United States. We investigated the association between federal domestic HIV funding and age-adjusted HIV death rates by race/ethnicity in the United States during 1999-2017. METHODS: We analyzed HIV funding data from the Kaiser Family Foundation by federal fiscal year (FFY) and US age-adjusted death rates (AADRs) by race/ethnicity (Hispanic, non-Hispanic white, non-Hispanic black, and Asian/Pacific Islander and American Indian/Alaska Native [API+AI/AN]) from Centers for Disease Control and Prevention WONDER detailed mortality files. We fit joinpoint regression models to estimate the annual percentage change (APC), average APC, and changes in AADRs per billion US dollars in HIV funding, with 95% confidence intervals (CIs). For 19 data points, the number of joinpoints ranged from 0 to 4 on the basis of rules set by the program or by the user. A Monte Carlo permutation test indicated significant (P < .05) changes at joinpoints, and 2-sided t tests indicated significant APCs in AADRs. RESULTS: Domestic HIV funding increased from $10.7 billion in FFY 1999 to $26.3 billion in FFY 2017, but AADRs decreased at different rates for each racial/ethnic group. The average rate of change in AADR per US billion dollars was -9.4% (95% CI, -10.9% to -7.8%) for Hispanic residents, -7.8% (95% CI, -9.0% to -6.6%) for non-Hispanic black residents, -6.7% (95% CI, -9.3% to -4.0%) for non-Hispanic white residents, and -5.2% (95% CI, -7.8% to -2.5%) for non-Hispanic API+AI/AN residents. CONCLUSIONS: Increased domestic HIV funding was associated with faster decreases in age-adjusted HIV death rates for Hispanic and non-Hispanic black residents than for residents in other racial/ethnic groups. Increasing US HIV funding could be associated with decreasing future racial/ethnic disparities in the rate of HIV-related deaths.

Benchmarking the Cost-Effectiveness of Interventions Delaying Diabetes: A Simulation Study Based on NAVIGATOR Data.

OBJECTIVE: To estimate using the UK Prospective Diabetes Study Outcomes Model Version 2 (UKPDS-OM2) the impact of delaying type 2 diabetes onset on costs and quality-adjusted life expectancy using trial participants who developed diabetes in the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) study. RESEARCH DESIGN AND METHODS: We simulated the impact of delaying diabetes onset by 1-9 years, utilizing data from the 3,058 of 9,306 NAVIGATOR trial participants who developed type 2 diabetes. Costs and utility weights associated with diabetes and diabetes-related complications were obtained for the U.S. and U.K. settings, with costs expressed in 2017 values. We estimated discounted lifetime costs and quality-adjusted life years (QALYs) with 95% CIs. RESULTS: Gains in QALYs increased from 0.02 (U.S. setting, 95% CI 0.01, 0.03) to 0.15 (U.S. setting, 95% CI 0.10, 0.21) as the imposed time to diabetes onset was increased from 1 to 9 years, respectively. Savings in complication costs increased from $1,388 (95% CI $1,092, $1,669) for a 1-year delay to $8,437 (95% CI $6,611, $10,197) for a delay of 9 years. Interventions costing up to $567-$2,680 and £201-£947 per year would be cost-effective at $100,000 per QALY and £20,000 per QALY thresholds in the U.S. and U.K., respectively, as the modeled delay in diabetes onset was increased from 1 to 9 years. CONCLUSIONS: Simulating a hypothetical diabetes-delaying intervention provides guidance concerning the maximum cost and minimum delay in diabetes onset needed to be cost-effective. These results can inform the ongoing debate about diabetes prevention strategies and the design of future intervention studies.

HOPE for Rational Statin Allocation for Primary Prevention: A Coronary Artery Calcium Picture Is Worth 1000 Words.

Allocation of statin therapy for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in borderline- and intermediate-risk patients has traditionally been based on population-based global risk assessment and other clinical and laboratory characteristics. Patient-specific treatment decisions are needed to provide maximal benefit and avoid unnecessary treatment. Guideline-based lipid management proposes that coronary artery calcium scoring is reasonable to implement in patients with a 10-year risk of 5.0% to 19.9% (borderline to intermediate risk) by using the pooled cohort equations when the decision about whether to initiate statin therapy is uncertain. We report data from both observational studies and a large primary prevention randomized controlled trial that support the position that this decision is, in fact, uncertain in about half of such patients because of risk misclassification. Such misclassification can be largely avoided by more widespread implementation of coronary calcium scoring, which helps to identify those with coronary artery calcium scores of 0, a finding associated with a less than 5.0% 10-year probability of an ASCVD event. Deferral of statin therapy in such patients, in the absence of smoking, diabetes, or a family history of premature ASCVD, provides more individualized and appropriate care and avoids the expense and potential adverse effects of statin therapy in those with low potential for absolute risk reduction. A rationale is also provided for the importance of coronary artery calcium scoring in women 50 years and older, possibly in place of 1 screening mammogram in women at least 55 years of age to avoid incremental radiation exposure, on the basis of the substantially higher lifetime risk of morbidity and mortality from ASCVD than from breast cancer. In patients with borderline or intermediate ASCVD risk, coronary artery calcium scoring should be used, whenever possible, as an aid to rational statin allocation for the primary prevention of ASCVD.

Rationing social contact during the COVID-19 pandemic: Transmission risk and social benefits of US locations.

To prevent the spread of coronavirus disease 2019 (COVID-19), some types of public spaces have been shut down while others remain open. These decisions constitute a judgment about the relative danger and benefits of those locations. Using mobility data from a large sample of smartphones, nationally representative consumer preference surveys, and economic statistics, we measure the relative transmission reduction benefit and social cost of closing 26 categories of US locations. Our categories include types of shops, entertainments, and service providers. We rank categories by their trade-off of social benefits and transmission risk via dominance across 13 dimensions of risk and importance and through composite indexes. We find that, from February to March 2020, there were larger declines in visits to locations that our measures indicate should be closed first.

A computer-guided quality improvement tool for primary health care: cost-effectiveness analysis based on TORPEDO trial data.

OBJECTIVE: To assess the cost-effectiveness of a computer-guided quality improvement intervention for primary health care management of cardiovascular disease (CVD) in people at high risk. DESIGN: Modelled cost-effectiveness analysis of the HealthTracker intervention and usual care for people with high CVD risk, based on TORPEDO trial data on prescribing patterns, changes in intermediate risk factors (low-density lipoprotein cholesterol, systolic blood pressure), and Framingham risk scores. PARTICIPANTS: Hypothetical population of people with high CVD risk attending primary health care services in a New South Wales primary health network (PHN) of mean size. INTERVENTION: HealthTracker, integrated into health care provider electronic health record systems, provides real time decision support, risk communication, a clinical audit tool, and a web portal for performance feedback. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs): difference in costs of the intervention and usual care divided by number of CVD events averted with HealthTracker. RESULTS: The estimated numbers of major CVD events over five years per 1000 patients at high CVD risk were lower in PHNs using HealthTracker, both for patients with prior CVD events (secondary prevention; 259 v 267 with usual care) and for those without prior events (primary prevention; 168 v 176). Medication costs were higher and hospitalisation costs lower with HealthTracker than with usual care for both primary and secondary prevention. The estimated ICER for one averted CVD event was $7406 for primary prevention and $17 988 for secondary prevention. CONCLUSION: Modelled cost-effectiveness analyses provide information that can assist decisions about investing in health care quality improvement interventions. We estimate that HealthTracker could prevent major CVD events for less than $20 000 per event averted. TRIAL REGISTRATION (TORPEDO): Australian New Zealand Clinical Trials Registry, ACTRN 12611000478910.

Role for risk factor treatment in the management of atrial fibrillation.

Atrial fibrillation is the most common arrhythmia in the world with continued rising prevalence, significant morbidity and mortality, and a substantial financial burden. It has been associated with numerous modifiable risk factors and chronic medical conditions. Treatment of these modifiable risk factors has improved rhythm control of atrial fibrillation as well as demonstrated cost-effectiveness. Primary prevention of underlying chronic disease should be incorporated into the treatment paradigm for AF. Comprehensive management with integrated care including the patient, allied health professionals, primary care physicians, and specialists will be needed to reverse the epidemiological trends, improve quality of life, and mortality.