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

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Weintraub reported receiving grants from Amarin during the conduct of the study. Dr Bhatt reported serving as the REDUCE-IT chair and principal investigator during the conduct of the study; and receiving grants from Amarin, AstraZeneca, Bristol Myers Squibb, Eisai, Ethicon, Medtronic, sanofi aventis, The Medicines Company, Roche, Pfizer, Forest Laboratories/AstraZeneca, Ischemix, Amgen, Lilly, Chiesi, Ironwood, Regeneron, Idorsia, Synaptic, Fractyl, Afimmune, Ferring Pharmaceuticals, Lexicon, Contego Medical, Owkin, HLS Therapeutics, 89bio, Garmin, Stasys, Faraday Pharmaceuticals, and Abbott; performing unfunded research for FlowCo, Takeda, and Merck; serving on the advisory board for Medscape Cardiology, Elsevier Practice Update Cardiology, Level Ex, Regado Biosciences, and Stasys; serving on the board of directors for Boston VA Research Institute; serving as deputy editor for Clinical Cardiology; serving as a site coinvestigator for Abbott, Biotronic, St Jude Medical (now Abbott), Svelte, CSI, and Philips; receiving grants from and serving on the advisory board for PLx Pharma, Cardax, PhaseBio, Novo Nordisk, Cereno Scientific, CellProthera, MyoKardia/Bristol Myers Squibb, Janssen, and NirvaMed; receiving grants from and serving as a site co-investigator for Boston Scientific; receiving personal fees and nonfinancial support from and serving as a trustee for American College of Cardiology; receiving grants and personal fees from and serving on the advisory board for Boehringer Ingelheim; personal fees from Duke Clinical Research Institute, Mayo Clinic, Population Health Research Institute, Belvoir Publications, Slack Publications, WebMD, Elsevier, HMP Global, Harvard Clinical Research Institute (now Baim Institute for Clinical Research), Journal of the American College of Cardiology, Cleveland Clinic, TobeSoft, Bayer, Medtelligence/ReachMD, CSL Behring, MJH Life Sciences, Level Ex, K2P, Canadian Medical and Surgical Knowledge Translation Research Group, Arnold and Porter law firm, Piper Sandler, Cowen and Company, and Mount Sinai School of Medicine; personal fees and nonfinancial support from Society of Cardiovascular Patient Care; and nonfinancial support from American Heart Association outside the submitted work. Dr Zhang reported receiving personal fees from MedStar outside the submitted work. Dr Bress reported receiving grants from Amarin during the conduct of the study. Dr King reported receiving personal fees from MedStar Health which were funded by Amarin Corporation during the conduct of the study. Dr Tajeu reported receiving grants from the National Institutes of Health (NIH)/National Institute of Diabetes and Digestive and Kidney Diseases and grants and personal fees from the NIH/National Heart, Lung, and Blood Institute during the conduct of the study. Dr Derington reported receiving research funds directly to institution from Amgen Inc and Amarin Corporation outside the submitted work. Mr Johnson and Ms Andrade reported being employees of Optum and that Amarin funded analyses performed by Optum during the conduct of the study. Dr Steg reported receiving personal fees from Amarin during the conduct of the study; personal fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Idorsia, Novartis, Novo Nordisk, Sanofi, and Servier; and grants from Sanofi, Servier, and Bayer outside the submitted work; in addition, Dr Steg had a patent for use of alirocumab to reduce cardiovascular risk issued to Sanofi with no royalties. Dr Miller reported receiving personal fees from Amarin during the conduct of the study and personal fees from Amarin outside the submitted work. Dr Brinton reported receiving personal fees from Amarin during the conduct of the study; and personal fees from Esperion, AstraZeneca, Kowa, and from Pfizer outside the submitted work; grants from Regeneron; and serving as a speaker and/or consultant to 89bio, Amgen, Amryt, Dalcor, Medicure, and Novartis. Dr Jacobson reported receiving personal fees from Amarin during the conduct of the study and personal fees from Amgen, Esperion, Novartis, Regeneron and AstraZeneca outside the submitted work. Dr Tardif reported receiving grants from Amarin and personal fees from HLS Pharmaceuticals during the conduct of the study; and grants and personal fees from AstraZeneca and DalCor Pharmaceuticals; grants from Ceapro, Esperion, Novartis, Pfizer, RegenXBio, and Sanofi; holding minor equity interest in DalCor Pharmaceuticals; and personal fees from Pendopharm, outside the submitted work; in addition, Dr Tardif had a patent for pharmacogenomics-guided cholesteryl ester transfer protein inhibtion issued to DalCor Pharmaceuticals, a patent for use of colchicine after myocardial infarction pending, and a patent for genetic determinants of response to colchicine pending. Dr Ballantyne reported receiving personal fees from Amarin during the conduct of the study; grants from Akcea, Amgen, Arrowhead, Esperion, Ionis, Novartis, and Regeneron; grant/research support (to his institution) and personal fees from Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Esperion, Genentech, Gilead, Illumina, Matinas BioPharma Inc, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Sanofi-Synthelabo outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Cost-effectiveness Planes During the Trial Period Using National Inpatient Sample Costs for Events

A, Cost-effectiveness plane for SSR cost. B, Cost-effectiveness plane for wholesale acquisition cost (WAC). C, Acceptability curve for SSR cost. D, Acceptability curve for WAC. QALY indicates quality-adjusted life-year; and WTP, willingness-to-pay.

Figure 2.. Cost-effectiveness Planes Over the Lifetime Using National Inpatient Sample Costs for Events

A, Cost-effectiveness plane for SSR cost. B, Cost-effectiveness plane for wholesale acquisition cost (WAC). C, Acceptability curve for SSR cost. D, Acceptability curve for WAC. QALY indicates quality-adjusted life-year; and WTP, willingness-to-pay.

Figure 3.. Icosapent Ethyl Daily Costs for Various Willingness-to-Pay (WTP) Thresholds

A, Costs during the trial period. B, Costs over the lifetime. NADAC indicates National Average Drug Acquisition Cost; VA, Veterans Administration; and WAC, wholesale acquisition cost.

Figure 4.. Tornado Diagrams for Incremental Cost-effectiveness Ratio (ICER)

A, ICER during the trial period using SSR Health net cost (SSR cost). B, ICER during the trial period using wholesale acquisition cost (WAC). C, ICER over the lifetime using SSR cost. D, ICER over the lifetime using WAC. Gray bar indicates low value, and orange bar indicates high value, separated by central line (ICER).