Efficacy and Safety of the PCSK9 Inhibitor Evolocumab in Patients with Mixed Hyperlipidemia

Rosenson RS, Jacobson TA, Preiss D, et al.
Cardiovasc Drugs Ther 2016;published online ahead of print

Background

Evolocumab, a PCSK9 inhibitor, significantly reduces LDL-C and other atherogenic lipid fractions in individuals with different lipid phenotypes, various levels of cardiovascular (CV) risk, and diverse baseline statin therapies [1-7]. Mixed hyperlipidaemia is characterised by elevated triglyceride (TG) (≥1.7 mmol/L [150 mg/dL] to <4.5mmol/L [400 mg/dL]) and LDL-C levels (≥2.0 mmol/L [75 mg/dL]), with increased serum concentrations of particles originating from either chylomicrons or very low–density lipoprotein (VLDL) [8].
It is not known whether evolocumab might significantly decrease LDL-C levels in patients with increased circulating levels of TGs and remnant-like lipoproteins.
In this analysis, the efficacy and safety of evolocumab (140 mg every 2 weeks or 420 mg monthly) in participants from phase 2 and 3 trials with mixed hyperlipidaemia (elevated LDL-C and TGs, total n = 1148) were evaluated, and compared with individuals with hypercholesterolaemia only (elevated LDL-C, normal triglycerides, total n = 1998). In addition, comparisons with participants meeting LDL-C, non–HDL-C and ApoB thresholds were conducted. Within the cohort, different patient groups were used to investigate efficacy or safety.

Main results

• The treatment difference (mean percentage change in LDL-C, from baseline to the mean LDL-C of week 10 and 12) for evolocumab-treated participants was approximately −67% vs. placebo and −42% vs. ezetimibe with elevated TGs, and −65% vs. placebo and −39% vs. ezetimibe (all P < 0.001) without elevated TG levels.
• Treatment differences for evolocumab vs. placebo and ezetimibe followed a similar pattern for non–HDL-C, ApoB, triglycerides, and HDL-C.
• A higher percentage of participants with elevated TGs were classed as National Cholesterol Education Program (NCEP) high-risk (41%) compared with participants without elevated triglycerides (30% NCEP high-risk).

• A similarly high proportion of evolocumab-treated, NCEP III–high-risk patients with and without elevated TGs achieved the target of LDL-C <1.8 mmol/L (70 mg/dL): 82% vs. 81%, respectively and LDL-C <2.6 mmol/L (100 mg/dL): 92% vs. 92%, respectively.

• Significantly more participants without elevated TGs achieved the ApoB targets, compared with participants with elevated TGs (P < 0.05), the non–HDL-C target of <2.6 mmol/L (100 mg/dL), compared with participants with elevated TGs (85 % vs. 77 %; P < 0.05).
• Evolocumab was generally well tolerated. Rates of adverse events were balanced between evolocumab vs. placebo or ezetimibe.  

Conclusion

Similar to hypercholesterolaemia patients without elevated triglycerides, the PCSK9 inhibitor evolocumab was well tolerated and associated with significant reductions of atherogenic lipids including LDL-C, non–HDL-C, and ApoB, compared with placebo and ezetimibe in mixed hyperlipidaemia patients with elevated triglyceride levels.

Find this article online at Cardiovasc Drugs Ther

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