Topics:
1. Limitations of the EVAPORATE Trial
2. Triglyceride Levels & REDUCE-IT trial outcomes
3. Stroke Rate & REDUCE-IT trial
Eric Roehm, MD, Oct. 2020
Limitations of the EVAPORATE* trial findings
*EVAPORATE1 (Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy)
The EVAPORATE trial examines serial CT coronary angiography findings for a Vascepa treatment group vs. a mineral oil placebo group.1 Coronary plaque CT data from this trial suffers the same limitation as REDUCE-IT* in that a mineral oil placebo may potentially worsen vascular findings secondary to the effects of inflammation resulting from mineral oil intake.
*REDUCE-IT2 is named “Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia”
Baseline triglyceride levels & CV outcomes
in REDUCE-IT trial.
Is the substantial reduction in cardiovascular events (CV) in REDUCE-IT the result of the study population having high triglycerides on trial entry?
That does not appear to be the case. Approximately 10% of the study group in REDUCE-IT had baseline triglycerides <150mg/dL. The reduction in CV events as per hazard ratio was similar for participants with baseline triglycerides above or below 150mg/dL.2
Similarly, for participants with baseline triglycerides above or below 200mg/dL, the reduction of CV events was similar for participants with triglycerides ≥200mg/dL and <200mg/dL2
The subgroup of the trial participants with baseline triglycerides ≥200 mg/dL and HDL ≤35 mg/dL had a statistically significantly greater reduction in CV events as per hazard ratio than those with triglycerides <200mg/dL and HDL >35mg/dL.2 Whether this was the result of a subgroup being selected that more strongly benefited from the positive effects of icosapent ethyl or were more adversely affected by the potential negative effects of mineral oil is not known.
Stroke Rate Reduction in REDUCE-IT is a First for a Omega-3 Trial. Possible Reason:
There was a statistically significant reduction in overall stroke rate in the REDUCE-IT treatment group2 that had never been seen before in a large randomized omega-3 trial. Is this unique finding of a reduction in overall stroke rate because of the study medication, treatment group, or the negative effects of the mineral oil placebo?
(Of note, in a JELIS* trial post-hoc analysis3, a reduction in recurrent stroke was found that may simply be a chance finding resulting from the vagaries of post-hoc analysis. However, the JELIS trial4 did not show a reduction in overall, ischemic, or hemorrhagic stroke4.)
*JELIS (Japan Eicosapentaenoic Acid Lipid Intervention Study)4
References:
1.Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy (EVAPORATE). Accessed Sept. 2020. https://www.tctmd.com/news/evaporate-icosapent-ethyl-may-slow-atherosclerosis-progression
2. Bhatt DL, Steg PG, Miller M, et al. for the REDUCE-IT Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med 2019;380:11-22.
3. Reduction in the recurrence of stroke by eicosapentaenoic acid for hypercholesterolemic patients: subanalysis of the JELIS trial Tanaka K, Ishikawa Y, Yokoyama M, et al. Stroke 2008:39:2052-8.
4. Yokoyama M, Origasa H, Matsuzaki M, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS):
