The effect of elevated triglycerides and purified eicosapentaenoic acid ethyl ester (EPA) for cardiovascular risk reduction in the UK Biobank population

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Abstract Elevated plasma triglycerides (TG) are associated with insulin resistance, metabolic syndrome and major adverse cardiovascular events (MACE). Elevated plasma TG (>150 and 200–499 mg/dL) were recently reported to be a predictor of heart failure in patients with coronary heart disease on statin therapy with a respective 19% and 24% risk increase compared to normal TG levels. REDUCE-IT was a major double-blind randomised controlled trial that tested a novel formulation of highly purified eicosapentaenoic acid ethyl ester (EPA) in 8179 patients with elevated TG on statin therapy. In the trial, daily 4g of EPA lowered MACE by an absolute rate of 4.8% compared to a placebo over a median 4.9-year follow-up. This reflected a 25% risk reduction in MACE and a number needed to treat of 21. EPA recently received significant public attention in late 2019 as the FDA has approved it for secondary prevention and high-risk primary prevention of cardiovascular disease (CVD) in patients with elevated TG that match the trial criteria in the USA. We aimed to investigate the risk reduction in MACE from using EPA in the UK population. We used the UK BioBank, a panomic resource following 500,000 participants over >10 years, with similar age and sex adjusted rates of CVD as the UK population. We first calculated the hazard ratios and Kaplan-Meier survival curves by deciles of increasing TG for incidence of combined CV outcomes: stroke, coronary heart disease, and atherosclerosis. Non-linear CoxPH and DeepSurvival models were trained using different variables from >200,000 UK BioBank participants' data. C-index with standard error and confidence interval estimated with bootstrap sampling ensured quality control. We then matched the UK Biobank population with the REDUCE-IT inclusion criteria and estimated the reduction of combined cardiovascular outcomes if EPA was approved in this population. Hazard ratios increased for TG levels to 5.44 between the 10th decile, and the 1st decile TG level, which was used as baseline. 3563 UK Biobank participants matched with the REDUCE-IT criteria. With the assumption that EPA would have the same effect on the UK Biobank population, we estimate that if the participants were taking EPA, only 29% of the risk group versus actual 37% would have suffered an outcome within the UK Biobank follow-up period. This means that 289 less individuals would have suffered an event instead of the recorded 1318, for a total of 1037. That means according to the number needed to treat analysis, 13 patients would need to be treated to prevent 1 patient from experiencing an event. Elevated TG increase risk for CV events in the UK Biobank population. Purified EPA might become an important tool in our arsenal for CVD secondary and primary prevention. Survival Curves & CI of TG for CVD Funding Acknowledgement Type of funding source: None