Publications by Year: 2019

To assess the frequency and costs of revascularization procedures in patients with stable ischemic heart disease (SIHD) initiating ranolazine versus traditional antianginals. Adults (≥18 years) with a diagnosis of SIHD who initiated ranolazine or a traditional antianginal (beta-blocker [BB], calcium channel blocker [CCB], or long-acting nitrate [LAN]) as second or third line therapy between 2008 and 2016, were selected from the IBM MarketScan Databases. Inverse probability weighting based on propensity score was employed to balance the ranolazine and traditional antianginals cohorts on patient clinical characteristics. Outcomes assessed were frequency and total cost of revascularization procedures over a 12-month follow-up. A total of 108,741 patients with SIHD were included. Of these, 18% initiated treatment with ranolazine, 21% received BBs, 24% received CCBs, and 37% were treated with LANs. Revascularization rates were significantly lower in ranolazine patients (11%) than in BB (16%) and LAN (14%) patients (both p <0.001), and more comparable to CCB patients (10%; p = 0.007). Compared with BB and LAN, those in the ranolazine cohort were less likely to have a revascularization procedure during hospitalization and had a shorter length of stay if hospitalized (all p <0.001). The mean healthcare costs associated with revascularization were lower in ranolazine patients ($2,933) than in BB ($4,465) and LAN ($3,609) patients (p <0.001), but similar to CCB patients ($2,753; p = 0.29). In conclusion, ranolazine treatment in patients with SIHD was associated with fewer revascularization procedures and lower associated healthcare costs compared with patients initiating BB or LAN, and comparable to patients initiating CCBs.

BACKGROUND: The ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial included participants with a recent acute coronary syndrome. Compared with participants receiving statins alone, those receiving a statin plus alirocumab had lower rates of a composite outcome including myocardial infarction (MI), stroke, and death.

OBJECTIVE: To determine the cost-effectiveness of alirocumab in these circumstances.

DESIGN: Decision analysis using the Cardiovascular Disease Policy Model.

DATA SOURCES: Data sources representative of the United States combined with data from the ODYSSEY Outcomes trial.

TARGET POPULATION: U.S. adults with a recent first MI and a baseline low-density lipoprotein cholesterol level of 1.81 mmol/L (70 mg/dL) or greater.

TIME HORIZON: Lifetime.

PERSPECTIVE: U.S. health system.

INTERVENTION: Alirocumab or ezetimibe added to statin therapy.

OUTCOME MEASURES: Incremental cost-effectiveness ratio in 2018 U.S. dollars per quality-adjusted life-year (QALY) gained.

RESULTS OF BASE-CASE ANALYSIS: Compared with a statin alone, the addition of ezetimibe cost $81 000 (95% uncertainty interval [UI], $51 000 to $215 000) per QALY. Compared with a statin alone, the addition of alirocumab cost $308 000 (UI, $197 000 to $678 000) per QALY. Compared with the combination of statin and ezetimibe, replacing ezetimibe with alirocumab cost $997 000 (UI, $254 000 to dominated) per QALY.

RESULTS OF SENSITIVITY ANALYSIS: The price of alirocumab would have to decrease from its original cost of $14 560 to $1974 annually to be cost-effective relative to ezetimibe.

LIMITATION: Effectiveness estimates were based on a single randomized trial with a median follow-up of 2.8 years and should not be extrapolated to patients with stable coronary heart disease.

CONCLUSION: The price of alirocumab would have to be reduced considerably to be cost-effective. Because substantial reductions already have occurred, we believe that timely, independent cost-effectiveness analyses can inform clinical and policy discussions of new drugs as they enter the market.

PRIMARY FUNDING SOURCE: University of California, San Francisco, and Institute for Clinical and Economic Review.

IMPORTANCE: Medicaid expansion under the Patient Protection and Affordable Care Act led to one of the largest gains in health insurance coverage for nonelderly adults in the United States. However, its association with cardiovascular mortality is unclear.

OBJECTIVE: To investigate the association of Medicaid expansion with cardiovascular mortality rates in middle-aged adults.

DESIGN, SETTING, AND PARTICIPANTS: This study used a longitudinal, observational design, using a difference-in-differences approach with county-level data from counties in 48 states (excluding Massachusetts and Wisconsin) and Washington, DC, from 2010 to 2016. Adults aged 45 to 64 years were included. Data were analyzed from November 2018 to January 2019.

EXPOSURES: Residence in a Medicaid expansion state.

MAIN OUTCOMES AND MEASURES: Difference-in-differences of annual, age-adjusted cardiovascular mortality rates from before Medicaid expansion to after expansion.

RESULTS: As of 2016, 29 states and Washington, DC, had expanded Medicaid eligibility, while 19 states had not. Compared with counties in Medicaid nonexpansion states, counties in expansion states had a greater decrease in the percentage of uninsured residents at all income levels (mean [SD], 7.3% [3.2%] vs 5.6% [2.7%]; P < .001) and in low income strata (19.8% [5.5%] vs 13.5% [3.9%]; P < .001) between 2010 and 2016. Counties in expansion states had a smaller change in cardiovascular mortality rates after expansion (146.5 [95% CI, 132.4-160.7] to 146.4 [95% CI, 131.9-161.0] deaths per 100 000 residents per year) than counties in nonexpansion states did (176.3 [95% CI, 154.2-198.5] to 180.9 [95% CI, 158.0-203.8] deaths per 100 000 residents per year). After accounting for demographic, clinical, and economic differences, counties in expansion states had 4.3 (95% CI, 1.8-6.9) fewer deaths per 100 000 residents per year from cardiovascular causes after Medicaid expansion than if they had followed the same trends as counties in nonexpansion states.

CONCLUSIONS AND RELEVANCE: Counties in states that expanded Medicaid had a significantly smaller increase in cardiovascular mortality rates among middle-aged adults after expansion compared with counties in states that did not expand Medicaid. These findings suggest that recent Medicaid expansion was associated with lower cardiovascular mortality in middle-aged adults and may be of consideration as further expansion of Medicaid is debated.

OBJECTIVE: To assess the effect of cannabis legalisation on health effects and healthcare utilisation in Colorado (CO), the first state to legalise recreational cannabis, when compared with two control states, New York (NY) and Oklahoma (OK).

DESIGN: We used the 2010 to 2014 Healthcare Cost and Utilisation Project (HCUP) inpatient databases to compare changes in rates of healthcare utilisation and diagnoses in CO versus NY and OK.

SETTING: Population-based, inpatient.

PARTICIPANTS: HCUP state-wide data comprising over 28 million individuals and over 16 million hospitalisations across three states.

MAIN OUTCOME MEASURES: We used International Classification of Diseases-Ninth Edition codes to assess changes in healthcare utilisation specific to various medical diagnoses potentially treated by or exacerbated by cannabis. Diagnoses were classified based on weight of evidence from the National Academy of Science (NAS). Negative binomial models were used to compare rates of admissions between states.

RESULTS: In CO compared with NY and OK, respectively, cannabis abuse hospitalisations increased (risk ratio (RR) 1.27, 95% CI 1.26 to 1.28 and RR 1.16, 95% CI 1.15 to 1.17; both p<0.0005) post-legalisation. In CO, there was a reduction in total admissions but only when compared with OK (RR 0.97, 95% CI 0.96 to 0.98, p<0.0005). Length of stay and costs did not change significantly in CO compared with NY or OK. Post-legalisation changes most consistent with NAS included an increase in motor vehicle accidents, alcohol abuse, overdose injury and a reduction in chronic pain admissions (all p<0.05 compared with each control state).

CONCLUSIONS: Recreational cannabis legalisation is associated with neutral effects on healthcare utilisation. In line with previous evidence, cannabis liberalisation is linked to an increase in motor vehicle accidents, alcohol abuse, overdose injuries and a decrease in chronic pain admissions. Such population-level effects may help guide future decisions regarding cannabis use, prescription and policy.

OBJECTIVE: To determine any changes in total hospital revisits within 30 days of discharge after a hospital stay for medical conditions targeted by the Hospital Readmissions Reduction Program (HRRP).

DESIGN: Retrospective cohort study.

SETTING: Hospital stays among Medicare patients for heart failure, acute myocardial infarction, or pneumonia between 1 January 2012 and 1 October 2015.

PARTICIPANTS: Medicare fee-for-service patients aged 65 or over.

MAIN OUTCOMES: Total hospital revisits within 30 days of discharge after hospital stays for medical conditions targeted by the HRRP, and by type of revisit: treat-and-discharge visit to an emergency department, observation stay (not leading to inpatient readmission), and inpatient readmission. Patient subgroups (age, sex, race) were also evaluated for each type of revisit.

RESULTS: Our study cohort included 3 038 740 total index hospital stays from January 2012 to September 2015: 1 357 620 for heart failure, 634 795 for acute myocardial infarction, and 1 046 325 for pneumonia. Counting all revisits after discharge, the total number of hospital revisits per 100 patient discharges for target conditions increased across the study period (monthly increase 0.023 visits per 100 patient discharges (95% confidence interval 0.010 to 0.035)). This change was due to monthly increases in treat-and-discharge visits to an emergency department (0.023 (0.015 to 0.032) and observation stays (0.022 (0.020 to 0.025)), which were only partly offset by declines in readmissions (-0.023 (-0.035 to -0.012)). Increases in observation stay use were more pronounced among non-white patients than white patients. No significant change was seen in mortality within 30 days of discharge for target conditions (-0.0034 (-0.012 to 0.0054)).

CONCLUSIONS: In the United States, total hospital revisits within 30 days of discharge for conditions targeted by the HRRP increased across the study period. This increase was due to a rise in post-discharge emergency department visits and observation stays, which exceeded the decline in readmissions. Although reductions in readmissions have been attributed to improvements in discharge planning and care transitions, our findings suggest that these declines could instead be because hospitals and clinicians have intensified efforts to treat patients who return to a hospital within 30 days of discharge in emergency departments and as observation stays.

This study examines the insurance coverage and out-of-pocket costs to Medicare beneficiaries for the angiotensin receptor–neprilysin inhibitor sacubitril/valsartan.

BACKGROUND: Fewer than 25% of patients with atherosclerotic cardiovascular disease in countries of low and middle income (LMICs) use guideline-directed drugs for secondary prevention. A fixed-dose combination polypill might improve cardiovascular outcomes by increasing prescription rates and adherence, but the cost-effectiveness of this approach is uncertain.

METHODS: We developed microsimulation models to assess the cost-effectiveness of a polypill containing aspirin, lisinopril, atenolol, and simvastatin for secondary prevention of atherosclerotic cardiovascular disease compared with current care in China, India, Mexico, Nigeria, and South Africa. We modelled baseline use of secondary prevention drugs on the Prospective Urban Rural Epidemiological study. In the intervention arm, we assumed that patients currently prescribed any prevention drug for atherosclerotic cardiovascular disease would receive the polypill instead, which would improve adherence by 32% (from a meta-analysis of two randomised trials in LMICs). We assessed the cost-effectiveness of the polypill at prices in the public sector and on the retail market. Key outcomes were major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) over a 5-year period and the incremental cost-effectiveness ratio (ICER) from the perspective of the health-care sector and a lifetime analytical horizon. We assumed a cost-effectiveness threshold equal to each country's per capita gross domestic product (GDP) per disability-adjusted life-year (DALY) averted. In sensitivity analyses, we examined the population health effect achievable by increasing the uptake of the polypill in the eligible population.

FINDINGS: Among adults aged 30-84 years with established atherosclerotic cardiovascular disease, adoption of the polypill for secondary prevention compared with current care was projected to avert 40-54 major adverse cardiovascular events for every 1000 patients treated for 5 years and produce between three and ten additional serious adverse events. Assuming public-sector pharmaceutical prices, the ICER of the polypill compared with current care over a lifetime analytical horizon was Int$168 (95% UI 55 to 337) per DALY averted in China, $154 (57 to 289) in India, $88 (15 to 193) in Mexico, $364 (147 to 692) in Nigeria, and $64 (cost-saving to 203) in South Africa, amounting to 0·4-6·2% of the per capita GDP in these countries. The ICER of the polypill compared with current care increased to 3·3-14·6% of the per capita GDP at retail market pharmaceutical prices. Use of the polypill at current rates of prescription of secondary prevention drugs would produce modest health benefits, reducing DALYs from atherosclerotic cardiovascular disease among patients with established disease by 3·1-10·1% over 10 years. Increasing use to 50% or 75% of the eligible population would produce substantially larger health gains (up to 24·3% atherosclerotic cardiovascular disease DALYs averted).

INTERPRETATION: The polypill is projected to be cost-effective compared with current care for secondary prevention of atherosclerotic cardiovascular disease in China, India, Mexico, Nigeria, and South Africa, particularly if it is made available at public-sector pricing. However, achieving meaningful improvements in cardiovascular health will require simultaneous investments in health infrastructure to increase the uptake of the polypill among patients with established atherosclerotic cardiovascular disease.

FUNDING: Richard A and Susan F Smith Center for Outcomes Research in Cardiology, Hellman Family Foundation, Department of Veterans Affairs, and University of California at San Francisco.

IMPORTANCE: American College of Cardiology/American Heart Association cholesterol guidelines prioritize primary prevention statin therapy based on 10-year absolute risk (AR10) of atherosclerotic cardiovascular disease (ASCVD). However, given the same AR10, patients with higher levels of low-density lipoprotein cholesterol (LDL-C) experience greater absolute risk reduction from statin therapy.

OBJECTIVES: To estimate the cost-effectiveness of expanding preventive statin treatment eligibility from standard care to patients at borderline risk (AR10, 5.0%-7.4%) for ASCVD and with high levels of LDL-C and to estimate cost-effectiveness of statin treatment across ranges of age, sex, AR10, and LDL-C levels.

DESIGN, SETTING, AND PARTICIPANTS: This study evaluated 100 simulated cohorts, each including 1 million ASCVD-free survey respondents (50% men and 50% women) aged 40 years at baseline. Cohorts were created by probabilistic sampling of the 1999-2014 US National Health and Nutrition Examination Surveys from the perspective of the US health care sector. The CVD Policy Model microsimulation version projected lifetime health and cost outcomes. Probability of first-ever coronary heart disease or stroke event was estimated by analysis of 6 pooled US cohort studies and recalibrated to match contemporary event rates. Other model variables were derived from national surveys, meta-analyses, and published literature. Data were analyzed from May 15, 2018, through June 10, 2019.

EXPOSURES: Four statin treatment strategies were compared: (1) treat all patients with AR10 of at least 7.5%, diabetes, or LDL-C of at least 190 mg/dL (standard care); (2) add treatment for borderline risk and LDL-C levels of 160 to 189 mg/dL; (3) add treatment for borderline risk and LDL-C levels of 130 to 159 mg/dL; and (4) add treatment for remainder of patients with AR10 of at least 5.0%. Statin treatment was also compared with no statin treatment in age, sex, AR10, and LDL-C strata.

MAIN OUTCOMES AND MEASURES: Lifetime quality-adjusted life-years (QALYs) and costs (2019 US dollars) were projected and discounted 3.0% annually. The primary outcome was the incremental cost-effectiveness ratio.

RESULTS: In these 100 simulated cohorts, each with 1 million patients aged 40 years at baseline (50% women and 50% men), adding preventive statins to individuals with borderline AR10 and LDL-C levels of 160 to 189 mg/dL would be cost-saving; further treating borderline AR10 and LDL-C levels of 130 to 159 mg/dL would also be cost-saving; and treating all individuals with AR10 of at least 5.0% would be highly cost-effective ($33 558/QALY) and would prevent the most ASCVD events. Within age, AR10, and sex categories, individuals with higher baseline LDL-C levels gained more QALYs from statin therapy. Cost-effectiveness increased with LDL-C level and AR10.

CONCLUSIONS AND RELEVANCE: In this study, lifetime statin treatment of patients in a hypothetical cohort with borderline ASCVD risk and LDL-C levels of 160 to 189 mg/dL was found to be cost-saving. Results suggest that treating all patients at borderline risk regardless of LDL-C level would likely be highly cost-effective.

In our increasingly cost-conscious health system, patients, clinicians, hospitals, and payers all agree about the urgent need to rein in runaway healthcare costs. High pharmaceutical costs make drugs unaffordable to many patients who may benefit from them, including some insured patients who face prohibitive out-of-pocket costs. Health systems and payers can use the systematic framework of cost-effectiveness analysis and estimated budgetary impact to prioritize the adoption of new therapies and technologies. In this review article, we discuss basic principles of cost-effectiveness research for practicing clinicians, the concept of cost-effectiveness versus affordability, other considerations relevant to resource allocation, and limitations of cost-effectiveness research. We use the example of lipid lowering therapies to discuss application of cost-effectiveness research in informing health care policy, its use for health care systems and in the development of clinical practice guidelines, and its implications for clinicians and patients. As clinicians and patients become more cognizant of the cost-implications of new therapies, professional societies can help improve the quality of decision-making by incorporating unbiased value statements into their expert guidelines.