Recent publications on Residual Risk

A number of posters added to the information about this novel lipid-modifying agent. As a follow-up to the clinical study in dyslipidaemic patients with elevated triglycerides, reported by Ishibashi et al,¹ pemafibrate was shown to reduce the particle number of triglyceride-rich chylomicrons, very low-density lipoproteins (VLDL) and small low-density lipoproteins (LDL), but increased large LDL and antiatherogenic high-density lipoproteins (HDL).²
A pooled analysis of phase II/III trials in 1255 patients, 957 treated with pemafibrate, showed a favourable safety profile consistent with that reported in other trials. The incidence of adverse events was comparable with placebo with no indication of any increase in adverse events with increasing dose, and there were no clinically meaningful changes in liver or renal function tests.³ In another study in 189 patients with a spectrum of renal function based on estimated glomerular filtration rate (ranging from <45 to ?90 ml/min/1.73 m2) there was no change in renal function in any cohort of patients over 52 weeks treatment with pemafibrate 0.2 mg twice daily.⁴
Furthermore, in separate studies, pemafibrate exposure was not dependent on the severity of renal dysfunction,⁵ and there was no need for dose adjustment in individuals with fatty liver disease.⁶ Concomitant treatment with pemafibrate and statins had no clinically meaningful effect on the systemic exposure on either agent.⁷
 
References
1. Ishibashi S et al. Effects of K-877, a novel selective PPAR? modulator (SPPARM?), in dyslipidaemic patients: A randomized, double blind, active- and placebo-controlled, phase 2 trial. Atherosclerosis 2016;249:36-43.
2. Yamashita S et al. Effect of selective PPAR? modulator K-877 on particle numbers of lipoprotein subclasses in dyslipidemic patients: analysis by HPLC and NMR lipoprofile 2 and 3. P1-095
3. Arai H et al. A pooled analysis of pemafibrate phase II/III clinical trials showed no significant increase in incidence of adverse events compared with placebo. P5-029
4. Yokote K et al. Long-term pemafibrate treatment was well tolerated in patients with dyslipidemia including those with kidney dysfunction. P5-049.
5. Hosford D, et al. The plasma concentration and pharmacokinetic parameters of pemafibrate did not increase in a creatine clearance-dependent manner. Poster P5-036
6. Hosford D et al. Dose adjustment should be considered for the administration of pemafibrate in patients with hepatic cirrhosis. Poster P5-037
7. Hounslow N et al. Pemafibrate minimally affected the systemic exposure of statins, and vice versa, in healthy male volunteers. Poster P5-052.
 
One key focus of the meeting was the role of visceral obesity in health, relating to cardiovascular disease and beyond. The R3i covered the Joint International Atherosclerosis Society (IAS)-International Chair on Cardiometabolic Risk (ICCR) satellite symposium on visceral adiposity and related atherogenic hypertriglyceridemia; check back for the highlights report from this key meeting.