IPE Reduces Atherogenic Lipid, Inflammatory Markers in Patients with Reduced Kidney Function, High Triglycerides

Krishnaswami Vijayaraghavan, MD

According to new data, icosapent ethyl (IPE; Vascepa, Amarin), has been shown to reduce potentially atherogenic lipid and inflammatory markers in patients with reduced kidney function and high triglycerides that were treated with statins.

The data were presented in 2 poster presentations at the National Kidney Foundation (NFK) 2018 Spring Clinical Meetings in Austin, Texas. Both posters were led by author Krishnaswami Vijayaraghavan, MD, the Medical Director, Congestive Heart Failure Program at the Abrazo Arizona Heart Hospital, in Phoenix.

“In the study presented at the NKF meeting, data shows significant improvement in inflammatory markers and atherogenic lipid biomarkers, as compared to placebo, in patients with reduced kidney function with use of an EPA only agent beyond statin therapy,” Vijayaraghavan told MD Magazine. “This was shown in this study without increasing the LDL-C levels. The clinical implications of this data are meaningful so far as a healthcare provider would want to address the larger picture of stabilization of a vulnerable state of higher cardiovascular event risk in this population.”

The data from the first presentation showed that compared with placebo, 4 g/day of IPE reduced triglycerides by —19.7% (P <.0001) and other lipids without affecting low-density lipoprotein cholesterol (LDL-C) levels in patients with diabetes and persistent triglycerides, estimated glomerular filtration rate (eFGR) <90 mL/min/1.73 m². These findings were consistent with the previous findings of the ANCHOR trial. Moreover, apolipoproteins and markers of oxidation and inflammation were also significantly improved.

“While we expected a reduction in triglyceride and non-HDL-C levels in this population, there were other markers that showed [a] significant reduction,” Vijayaraghavan said. “To me, the reduction of remnant lipoprotein cholesterol (RLP-C) by 30 % was pleasantly surprising. This is because RLP-C has recently been shown to be a risk factor for incident coronary events as well as atherosclerotic stroke.”

Additional data from the second poster showed that in statin-treated patients with reduced kidney function and persistent high triglycerides, eFGR <90 mL/min/1.73 m², when compared to placebo, a 4g daily dose of IPE reduced triglycerides and other potentially atherogenic and inflammatory markers without raising low-density cholesterol.

“The biggest takeaway from these data is the stronger belief in the residual risk beyond LDL-C,” Vijayaraghavan said. “Triglycerides, RLP-C, other atherogenic lipid markers as well as inflammatory markers have a role to play in plaque genesis and making them vulnerable for rupture causing a CV event. This is more so in that patient with CKD.”

“We are still struggling to figure out what it is that increases the CV risk in this population. While statins have not been impactful, the question comes up as to the agent of choice in CKD patients that will hopefully protect them,” he added.

Vijayaraghavan and colleagues both noted that more research is needed to elucidate the future risk of cardiovascular events in patients with reduced kidney function and high triglycerides despite being treated with statins. The findings of the REDUCE-IT trial will seek to determine this, Vijayaraghavan noted.

REDUCE-IT is the first multinational cardiovascular outcomes study that will evaluate the impact of prescription pure eicosapentaenoic acid therapy—or any triglyceride lowering therapy&mdash;as an add-on treatment to statins in patients with a high cardiovascular risk that have elevated triglyceride levels (150-499 mg/dL), despite statin therapy. It is also anticipated that a large portion of the patients enrolled in the study will have type 2 diabetes.