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Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results.
Cardiovasc Res. 2021 03 21; 117(4):1070-1077.CR

Abstract

AIMS

Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients.

METHODS AND RESULTS

EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40-115 mg/dL, and persistently high triglyceride levels (135-499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (-1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use.

CONCLUSION

EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial.

CLINICALTRIALS. GOVIDENTIFIER

NCT029226027.

Authors+Show Affiliations

Department of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, 1124 W Carson Street, CDCRC, Torrance, CA 90502, USA.Department of Internal Medicine, Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, UT, USA.Department of Internal Medicine, Brigham and Women's Hospital Heart & Vascular Center and Harvard Medical School, Boston, MA, USA.Department of Internal Medicine, Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, UT, USA. Department of Internal Medicine, Rocky Mountain University of Health Profession, Provo, UT, USA.Department of Internal Medicine, Intermountain Heart Institute, Intermountain Medical Center, Salt Lake City, UT, USA.Department of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, 1124 W Carson Street, CDCRC, Torrance, CA 90502, USA.Department of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, 1124 W Carson Street, CDCRC, Torrance, CA 90502, USA.Department of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, 1124 W Carson Street, CDCRC, Torrance, CA 90502, USA.Department of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, 1124 W Carson Street, CDCRC, Torrance, CA 90502, USA.Department of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, 1124 W Carson Street, CDCRC, Torrance, CA 90502, USA.Department of Medicine, Lundquist Institute at Harbor-UCLA Medical Center, 1124 W Carson Street, CDCRC, Torrance, CA 90502, USA.Department of Internal Medicine, California Cardiovascular Institute, Fresno, CA, USA.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32609331

Citation

Budoff, Matthew J., et al. "Effect of Icosapent Ethyl On Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides On Statin Therapy: a Prospective, Placebo-controlled Randomized Trial (EVAPORATE): Interim Results." Cardiovascular Research, vol. 117, no. 4, 2021, pp. 1070-1077.
Budoff MJ, Muhlestein JB, Bhatt DL, et al. Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results. Cardiovasc Res. 2021;117(4):1070-1077.
Budoff, M. J., Muhlestein, J. B., Bhatt, D. L., Le Pa, V. T., May, H. T., Shaikh, K., Shekar, C., Kinninger, A., Lakshmanan, S., Roy, S. K., Tayek, J., & Nelson, J. R. (2021). Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results. Cardiovascular Research, 117(4), 1070-1077. https://doi.org/10.1093/cvr/cvaa184
Budoff MJ, et al. Effect of Icosapent Ethyl On Progression of Coronary Atherosclerosis in Patients With Elevated Triglycerides On Statin Therapy: a Prospective, Placebo-controlled Randomized Trial (EVAPORATE): Interim Results. Cardiovasc Res. 2021 03 21;117(4):1070-1077. PubMed PMID: 32609331.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results. AU - Budoff,Matthew J, AU - Muhlestein,Joseph B, AU - Bhatt,Deepak L, AU - Le Pa,Viet T, AU - May,Heidi T, AU - Shaikh,Kashif, AU - Shekar,Chandana, AU - Kinninger,April, AU - Lakshmanan,Suvasini, AU - Roy,Sion K, AU - Tayek,John, AU - Nelson,John R, PY - 2020/06/23/accepted PY - 2020/7/2/pubmed PY - 2022/1/5/medline PY - 2020/7/2/entrez KW - Atherosclerosis KW - CT angiography KW - Fish oil KW - Progression KW - Randomized trial SP - 1070 EP - 1077 JF - Cardiovascular research JO - Cardiovasc Res VL - 117 IS - 4 N2 - AIMS: Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients. METHODS AND RESULTS: EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40-115 mg/dL, and persistently high triglyceride levels (135-499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (-1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use. CONCLUSION: EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial. CLINICALTRIALS. GOVIDENTIFIER: NCT029226027. SN - 1755-3245 UR - https://www.unboundmedicine.com/medline/citation/32609331/Effect_of_icosapent_ethyl_on_progression_of_coronary_atherosclerosis_in_patients_with_elevated_triglycerides_on_statin_therapy:_a_prospective_placebo_controlled_randomized_trial__EVAPORATE_:_interim_results_ L2 - https://academic.oup.com/cardiovascres/article-lookup/doi/10.1093/cvr/cvaa184 DB - PRIME DP - Unbound Medicine ER -