Cost-effectiveness of Icosapent Ethyl for High-risk Patients With Hypertriglyceridemia Despite Statin Treatment.

Importance: The Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial (REDUCE-IT) demonstrated the efficacy of icosapent ethyl (IPE) for high-risk patients with hypertriglyceridemia and known cardiovascular disease or diabetes and at least 1 other risk factor who were treated with statins. Objective: To estimate the cost-effectiveness of IPE compared with standard care for high-risk patients with hypertriglyceridemia despite statin treatment. Design, Setting, and Participants: An in-trial cost-effectiveness analysis was performed using patient-level study data from REDUCE-IT, and a lifetime analysis was performed using a microsimulation model and data from published literature. The study included 8179 patients with hypertriglyceridemia despite stable statin therapy recruited between November 21, 2011, and May 31, 2018. Analyses were performed from a US health care sector perspective. Statistical analysis was performed from March 1, 2018, to October 31, 2021. Interventions: Patients were randomly assigned to IPE, 4 g/d, or placebo and were followed up for a median of 4.9 years (IQR, 3.5-5.3 years). The cost of IPE was $4.16 per day after rebates using SSR Health net cost (SSR cost) and $9.28 per day with wholesale acquisition cost (WAC). Main Outcomes and Measures: Main outcomes were incremental quality-adjusted life-years (QALYs), total direct health care costs (2019 US dollars), and cost-effectiveness. Results: A total of 4089 patients (2927 men [71.6%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive IPE, and 4090 patients (2895 men [70.8%]; median age, 64.0 years [IQR, 57.0-69.0 years]) were randomly assigned to receive standard care. Treatment with IPE yielded more QALYs than standard care both in trial (3.34 vs 3.27; mean difference, 0.07 [95% CI, 0.01-0.12]) and over a lifetime projection (10.59 vs 10.35; mean difference, 0.24 [95% CI, 0.15-0.33]). In-trial, total health care costs were higher with IPE using either SSR cost ($18 786) or WAC ($24 544) than with standard care ($17 273; mean difference from SSR cost, $1513 [95% CI, $155-$2870]; mean difference from WAC, $7271 [95% CI, $5911-$8630]). Icosapent ethyl cost $22 311 per QALY gained using SSR cost and $107 218 per QALY gained using WAC. Over a lifetime, IPE was projected to be cost saving when using SSR cost ($195 276) compared with standard care ($197 064; mean difference, -$1788 [95% CI, -$9735 to $6159]) but to have higher costs when using WAC ($202 830) compared with standard care (mean difference, $5766 [95% CI, $1094-$10 438]). Compared with standard care, IPE had a 58.4% lifetime probability of costing less and being more effective when using SSR cost and an 89.4% probability of costing less than $50 000 per QALY gained when using SSR cost and a 72.5% probability of costing less than $50 000 per QALY gained when using WAC. Conclusions and Relevance: This study suggests that, both in-trial and over the lifetime, IPE offers better cardiovascular outcomes than standard care in REDUCE-IT participants at common willingness-to-pay thresholds.

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.

Add-On Therapies in Cardiovascular Disease: Reviewing ICER's Report and the Potential Effect on Payers.

DISCLOSURES: No outside funding supported this commentary. The authors have nothing to disclose.

The Effectiveness and Value of Rivaroxaban and Icosapent Ethyl as Additive Therapies for Cardiovascular Disease.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, Commonwealth Fund, California Health Care Foundation, National Institute for Health Care Management (NIHCM), New England States Consortium Systems Organization, Blue Cross Blue Shield of Massachusetts, Harvard Pilgrim Health Care, Kaiser Foundation Health Plan, and Partners HealthCare to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from Aetna, America's Health Insurance Plans, Anthem, Allergan, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Cambia Health Services, CVS, Editas, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, Health Partners, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Premera, Prime Therapeutics, Regeneron, Sanofi, Spark Therapeutics, and United Healthcare. Pearson is employed by ICER; Synnott was employed by ICER at the time of this report. Ollendorf, Campbell, and McQueen received grants from ICER for work on this review. Ollendorf also reports advisory board, consulting, and other fees from Sarepta Therapeutics, DBV Technologies, EMD Serono, Gerson Lehman Group, The CEA Registry Sponsors, Autolus, Analysis Group, Amgen, AbbVie, Cytokinetics, Aspen Institute/University of Southern California, and University of Colorado, unrelated to this review.

The cost-effectiveness of omega-3 polyunsaturated fatty acids - The Australian healthcare perspective.

OBJECTIVES: To examine the cost-effectiveness of a triglyceride lowering medication-icosapent ethyl added on to statin from Australian healthcare system perspective. METHODS: A Markov-model was developed using data from the pivotal trial of icosapent ethyl in a secondary prevention population. Probabilities of CVD events were derived and extrapolated from the published Kaplan-Meier curve using a valid algorithm. Management cost of CVD, health-related quality of life, and background non-CVD mortality were extracted from publicly available sources. Acquisition cost of icosapent ethyl from the United States was used in the current analysis. Australian patients with histories of CVD were modelled for a 25 year time horizon and costs and benefits were discounted. Sensitivity analyses (SA) were undertaken. Value of perfect information (VPI) was quantified. RESULTS: Treatment with icosapent ethyl was associated with both higher costs and benefits (i.e. quality-adjusted life year [QALY] and life year [LY]), resulting in an incremental cost-effectiveness ratio (ICER) of AUD59,036/QALY or AUD54,358/LY. Using the often quoted willingness-to-pay (WTP)/QALY of AUD50,000/QALY, icosapent ethyl was not considered cost-effective. SA showed that time horizon, drug cost, and discount rate were the key drivers of the ICER. Total monetary VPI for icosapent ethyl was over AUD15 million over 5 years. CONCLUSIONS: Patients with established CVD in whom level of triglycerides is high would benefit from the treatment using icosapent ethyl, however, it is not a cost-effective from an Australian healthcare system perspective. The government may consider subsidising this medication given the clinical need but at a discounted acquisition cost.

A novel cost-effectiveness model of prescription eicosapentaenoic acid extrapolated to secondary prevention of cardiovascular diseases in the United States.

OBJECTIVE: Given the substantial economic and health burden of cardiovascular disease and the residual cardiovascular risk that remains despite statin therapy, adjunctive therapies are needed. The purpose of this model was to estimate the cost-effectiveness of high-purity prescription eicosapentaenoic acid (EPA) omega-3 fatty acid intervention in secondary prevention of cardiovascular diseases in statin-treated patient populations extrapolated to the US. METHODS: The deterministic model utilized inputs for cardiovascular events, costs, and utilities from published sources. Expert opinion was used when assumptions were required. The model takes the perspective of a US commercial, third-party payer with costs presented in 2014 US dollars. The model extends to 5 years and applies a 3% discount rate to costs and benefits. Sensitivity analyses were conducted to explore the influence of various input parameters on costs and outcomes. RESULTS: Using base case parameters, EPA-plus-statin therapy compared with statin monotherapy resulted in cost savings (total 5-year costs $29,393 vs $30,587 per person, respectively) and improved utilities (average 3.627 vs 3.575, respectively). The results were not sensitive to multiple variations in model inputs and consistently identified EPA-plus-statin therapy to be the economically dominant strategy, with both lower costs and better patient utilities over the modeled 5-year period. LIMITATIONS: The model is only an approximation of reality and does not capture all complexities of a real-world scenario without further inputs from ongoing trials. The model may under-estimate the cost-effectiveness of EPA-plus-statin therapy because it allows only a single event per patient. CONCLUSION: This novel model suggests that combining EPA with statin therapy for secondary prevention of cardiovascular disease in the US may be a cost-saving and more compelling intervention than statin monotherapy.

Considerations for incorporating eicosapentaenoic and docosahexaenoic omega-3 fatty acids into the military food supply chain.

The U.S. military may consider exploring the inclusion of the long-chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in the diets of active duty military personnel. To be successful, certain challenges must be overcome including determining appropriate dosage, ensuring cost efficiency, and optimizing stability. To increase EPA and DHA intake, the military should consider using one of three strategies, including mandates or recommendations on omega-3 supplement usage, contracts to purchase commercially available foods for distribution in the food supply chain, or direct addition of EPA and DHA into currently consumed foods. This review presents the challenges and strategies and provides potential suggestions to the military to increase the likelihood of success.

A cost-effectiveness analysis of n-3 PUFA (Omacor) treatment in post-MI patients.

This study evaluates the cost-effectiveness of Omacor treatment as a standard prevention measure post-MI in the UK. A cost-effectiveness model was developed based on the GISSI-P trial, combining a survival and a Markov model, over a lifetime period. The base case results for Omacor, at 4 years and over a lifetime, respectively, were: cost [corrected] per QALY gained: pound15,189 and 3,723; [corrected] cost per life years gained (LYG): pound12,011 and pound2,812 [corrected] The cost per death avoided at 4 years was pound31,786. Deterministic and probabilistic sensitivity analyses did not change the base case results substantially. The use of Omacor as a standard post-MI prevention treatment seems warranted in the UK, both on the basis of its efficacy, which is in addition to other prophylactic treatments as evidenced by the results of the GISSI-P trial, and on cost-effectiveness grounds - both at 4 years and over a lifetime's time-horizon, using the current cost-effectiveness thresholds.