Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

A possible explanation for the contrasting results of REDUCE-IT vs. STRENGTH: cohort study mimicking trial designs

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Genome-wide association study reveals novel genetic loci: a new polygenic risk score for mitral valve prolapse

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Volunteer first responders for out-of-hospital cardiac arrest at home: the missing link for improved survival?

    Research output: Contribution to journalEditorialResearchpeer-review

  3. Risk of sports-related sudden cardiac death in women

    Research output: Contribution to journalReviewResearchpeer-review

  1. Monocyte count and soluble markers of monocyte activation in people living with HIV and uninfected controls

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Self-reported and genetically predicted coffee consumption and smoking in dementia: A Mendelian randomization study

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. New insights into the genetic etiology of Alzheimer's disease and related dementias

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Plasma high-density lipoprotein cholesterol and risk of dementia: observational and genetic studies

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

AIMS: We tested the hypothesis that the contrasting results for the effect of high-dose, purified omega-3 fatty acids on the prevention of atherosclerotic cardiovascular disease (ASCVD) in two randomized trials, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) vs. Long-Term Outcomes Study to Assess Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridaemia (STRENGTH), can be explained by differences in the effect of active and comparator oils on lipid traits and C-reactive protein.

METHODS AND RESULTS: In the Copenhagen General Population Study (CGPS) with 106 088 individuals, to mimic trial designs we analysed those who met key inclusion criteria in REDUCE-IT (n = 5684; ASCVD = 852) and STRENGTH (n = 6862; ASCVD = 697). Atherosclerotic cardiovascular disease incidence was followed for the median durations of REDUCE-IT and STRENGTH (4.9 and 3.5 years), respectively. When combining changes in plasma triglycerides, low-density lipoprotein cholesterol, and C-reactive protein observed in the active oil groups of the original studies, estimated hazard ratios for ASCVD in the CGPS were 0.96 [95% confidence interval 0.93-0.99] mimicking REDUCE-IT and 0.94 (0.91-0.98) mimicking STRENGTH. In the comparator oil groups, corresponding hazard ratios were 1.07 (1.04-1.10) and 0.99 (0.98-0.99). Combining these results, the active oil vs. comparator oil hazard ratio was 0.88 (0.84-0.93) in the CGPS mimicking REDUCE-IT compared to 0.75 (0.68-0.83) in the REDUCE-IT. The corresponding hazard ratio was 0.96 (0.93-0.99) in the CGPS mimicking STRENGTH compared to 0.99 (0.90-1.09) in STRENGTH.

CONCLUSION: The contrasting results of REDUCE-IT vs. STRENGTH can partly be explained by a difference in the effect of comparator oils (mineral vs. corn), but not of active oils [eicosapentaenoic acid (EPA) vs. EPA + docosahexaenoic acid], on lipid traits and C-reactive protein. The unexplained additional 13% risk reduction in REDUCE-IT likely is through other effects of EPA or mineral oil.

Original languageEnglish
JournalEuropean Heart Journal
Volume42
Issue number47
Pages (from-to)4807-4817
Number of pages11
ISSN0195-668X
DOIs
Publication statusPublished - 14 Dec 2021

Bibliographical note

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.

    Research areas

  • C-Reactive Protein, Cholesterol, LDL, Cohort Studies, Food, Humans, Triglycerides

ID: 71680552