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7 Hypertriglyceridaemia Triglyceride levels are associated with CV risk independent of LDL-C levels.102–104 With respect to pharmacological treatment of hypertriglyceridaemia, this Task Force continues to recommend statins as the first drug of choice to reduce CVD risk in high-risk patients.1 Currently available fibrates (gemfibrozil, fenofibrate, bezafibrate) have moderate triglyceride-lowering effects.105–107 Fenofibrate and bezafibrate lead to small decreases in LDL-C, but have not reduced MACE (MI, ischaemic stroke, CV mortality) or total mortality in patients treated with statins. A reduction in non-fatal MI was only seen in subgroup analyses of patients with atherogenic dyslipidaemia (low HDL-C and high triglycerides) in these trials.105,106 In a pre-specified subgroup analysis of the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) trial, fenofibrate was associated with a lower risk of lower-limb amputations, likely not mediated by lipid-related mechanisms.108 The PROMINENT (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN PatiENts With DiabeTes) trial recently showed that the selective peroxisome proliferator-activated receptor (PPAR-a) modulator pemafibrate109 did not reduce the risk of MACE in 10 497 patients with T2DM, mild-to-moderate hypertriglyceridaemia and low HDL-C levels; notably, pemafibrate increased ApoB and LDL-C levels in that trial. Overall, in contrast to the robust evidence of ASCVD risk reduction with LDL-C lowering therapies, the efficacy of triglyceride lowering with fibrates in reducing ASCVD risk has not been established. This Focused Update supports the Class IIb recommendations of the 2019 ESC/EAS Guidelines for the use of fenofibrate or bezafibrate.1 Fibrates are not indicated to lower serum cholesterol or LDL-C levels.110 Regarding n-3 polyunsaturated fatty acids (PUFAs), the STRENGTH trial was published following the publication of the 2019 ESC/EAS Guidelines.1 The trial failed to demonstrate benefit of a combined eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) preparation in 13 078 patients (70% with diabetes; 56% with established ASCVD) in lowering MACE (composite of cardiovascular death, nonfatal MI, non-fatal stroke, coronary revascularization, or unstable angina requiring hospitalization).8 1.0 0 Lifetime risk for major cardiovascular events mg/dL nmol/L Lipoprotein (a) 20 10 50 24 100 48 150 71 200 95 250 119 300 138 350 161 400 184 0 1.5 2.0 2.5 3.0 4.0 Hazard ratio (95% CI) Percentage of individualsa Figure 3 Association between Lp(a) levels and lifetime risk of major cardiovascular events. CI, confidence interval; Lp(a), lipoprotein (a). The risk of major CV events starts to slightly increase in individuals with Lp(a) levels >62 nmol/L (30 mg/dL), and the increase in risk becomes more pronounced in individuals with Lp(a) levels ≥105 nmol/L (50 mg/dL). The grey lines indicates the smoothed adjusted hazard ratio and 95% confidence interval (left y-axis) for lifetime risk for major CV events for a given Lp(a) concentration relative to the median Lp(a) in the population (data from the United Kingdom Biobank, sub-analysis including 415 274 white individuals).78 aThe blue line shows the frequency distribution of Lp(a) levels, with respective percentages indicated in the right y-axis (data from the United Kingdom Biobank including 443 180 individuals without prior atherosclerotic CVD).37 ESC Guidelines 4371 Downloaded from academic.oup.com/eurheartj/article/46/42/4359/8234482 by guest on 07 October 2026