Icosapent ethyl reduces cardiovascular risk across apolipoprotein b and fasting triglyceride rich lipoprotein levels

Abstract Background/Introduction Increased apolipoprotein B (ApoB) levels due to triglyceride rich lipoproteins (TRLs) are associated with increased cardiovascular risk, even when low-density lipoprotein cholesterol (LDL-C) levels are well controlled. In the REDUCE-IT cardiovascular outcomes trial, icosapent ethyl (IPE) showed cardiovascular risk reduction in patients with residual elevated triglycerides (TGs) persisting on statin therapy, but the impact of IPE on cardiovascular risk reduction across ApoB and TRL-cholesterol (TRL-C) strata is unclear. Purpose To study the impact of IPE on major adverse cardiovascular events (MACE) stratified by ApoB and fasting TRL-C. Methods REDUCE-IT was an international, double-blind, placebo-controlled study of 8,179 participants receiving statin therapy with established cardiovascular disease or age ≥ 50 years with diabetes and ≥ 1 additional risk factor, fasting TG level of 1.52 to 5.63 mmol/L (135 to 499 mg/dL) and LDL-C level of 1.06 to 2.59 mmol/L (41 to 100 mg/dL). Patients were randomized to receive 2 grams twice daily of IPE or matching placebo. Relationships between quartiles of baseline ApoB concentration, baseline fasting TRL-C and risk for first and total MACE were analyzed. Results Baseline ApoB and fasting TRL-C concentrations were available in 8,107 (99.1%) and 8,157 (99.7%) participants, respectively. Median baseline ApoB concentration was 0.82 g/L (IQR: 0.72 – 0.93 g/L) 82.0 mg/dL (IQR: 72.0 – 93.0 mg/dL) and median baseline fasting TRL-C concentration was 0.80 mmol/L (IQR: 0.69 – 0.95 mmol/L) 31.0 mg/dL (IQR: 26.6 – 36.8 mg/dL). From the first through fourth baseline quartiles of ApoB, IPE resulted in significant reductions in MACE, HR 0.72 (95% CI 0.58, 0.88), HR 0.73 (95% CI 0.59, 0.89), HR 0.76 (95% CI 0.63, 0.91), and HR 0.80 (95% CI 0.66, 0.97), respectively (all P ≤ 0.02) (Figure 1). The first quartile of fasting TRL-C had a borderline reduction in MACE (HR 0.82, 95% CI 0.67, 1.00) (P = 0.05) (Figure 2), in contrast to significant reductions above the 25th percentile, HR 0.74 (95% CI 0.60, 0.90), HR 0.79 (95% CI 0.65, 0.96), and HR 0.68 (95% CI 0.56, 0.82), from the second through fourth quartiles, respectively (all P ≤ 0.02). Conclusion IPE significantly reduced MACE across all quartiles of baseline ApoB and TRL-C concentrations above the 25th percentile.