Dataset Information

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.

SUBMITTER: Weintraub WS

PROVIDER: S-EPMC8844997 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description: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.

Project description:BackgroundInclisiran is a novel, cholesterol-lowering therapy, with a long duration of effect, administered every 6 months (subcutaneously by a healthcare professional). In the ORION-10 trial in US patients with atherosclerotic cardiovascular disease (ASCVD) in addition to maximum tolerated statins, with or without ezetimibe, inclisiran demonstrated statistically significant reductions in low-density lipoprotein cholesterol (LDL-C) of up to 51%. This is the first peer-reviewed publication to investigate the price at which inclisiran is cost effective in the US.ObjectiveThe aim of this study was to determine the maximum price at which inclisiran is cost effective in addition to standard of care, in US patients with ASCVD, versus standard of care alone, at different willingness-to-pay thresholds.Design, setting and participantsA lifetime Markov model from the US health system perspective, including 15 health states, was used to evaluate the cost effectiveness of inclisiran. The following states were separated by time from a previous cardiovascular event (0-1 years, 1-2 years, 2+ years ['stable']): initial, unstable angina, myocardial infarction, and stroke. Additional states included revascularization and death (cardiovascular or non-cardiovascular causes). Baseline risk of cardivoascular events were from US database sources or published literature. Reductions in LDL-C from inclisiran were from the ORION-10 trial. LDL-C reduction was used to adjust baseline risk of cardiovascular events, based on established relationships between 1 mmol/L reduction in LDL-C and decreases in cardiovascular events, from the Cholesterol Treatment Trialists studies. The population included adults with a history of ASCVD, and LDL-C ≥ 70 mg/dL, despite maximum tolerated doses of statin therapy.InterventionsInclisiran as an adjunct to standard of care, compared with standard of care alone.Main outcomes and measuresThe threshold price of inclisiran.ResultsInclisiran as an adjunct to standard of care resulted in threshold annual inclisiran prices of $6383, $9973, and $13,563 at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per quality-adjusted life-year, respectively. Probabilistic sensitivity analysis showed that at a threshold of $100,000 per QALY, inclisiran had a 100% probability of being cost effective, with an annual price below $9000. At the publicly available price of $3250 per dose, inclisiran was found to have an incremental cost-effectiveness ratio just above the $50,000 per QALY threshold, of $51,686.Conclusions and relevanceThis study identified the price at which inclisiran is cost effective for the US health system, at generally accepted willingness-to-pay thresholds.