Icosapent ethyl decreases triglycerides in reduced kidney function, diabetes

Harold M. Szerlip

Icosapent ethyl reduced triglycerides and other inflammatory and atherogenic markers in patients with reduced kidney function, persistent high triglycerides and either diabetes or elevated high-sensitivity C-reactive protein who were treated with statins, according to data presented at the National Kidney Foundation Spring Clinical Meetings.

Treatment with icosapent ethyl (Vascepa, Amarin) 4 g per day did not raise LDL and had no negative effect on renal function.

“Residual cardiovascular risk remains in some patients despite optimized statin therapy and may necessitate add-on therapy to reduce this risk,” Krishnaswami Vijayaraghavan, MD, FACC, FACP, FNLA, FHFSA, medical director of the congestive heart failure program at Abrazo Arizona Heart Hospital in Phoenix, told Cardiology Today. “Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, lowers plasma triglyceride levels without raising low-density lipoprotein cholesterol levels and has potential beneficial effects on atherosclerotic plaques. The mechanistic behavior of the EPA agent icosapent ethyl is fascinating. Animal studies have shown that EPA reduces levels of proinflammatory cytokines and chemokines. In clinical trials utilizing a wide spectrum of plaque imaging modalities, EPA has shown beneficial effects on plaque characteristics. Studies of patients with coronary artery disease receiving statin therapy suggest that EPA may decrease plaque vulnerability and prevent plaque progression.”

Triglyceride reduction in diabetes

Harold M. Szerlip, MD, FACP, FCCP, FASN, FNKF, chief of the nephrology division and director of the nephrology fellowship program at Baylor University Medical Center in Dallas, and colleagues analyzed data from the ANCHOR trial of 198 patients with increased CVD risk who were treated with statins and had triglycerides between 200 mg/dL and 499 mg/dL even with LDL levels between 40 mg/dL and 99 mg/dL. In this analysis, patients also had diabetes and an estimated glomerular filtration rate (eGFR) less than 90 mL/min/1.73 m² for more than 3 months.

Patients were assigned 4 g per day of icosapent ethyl (n = 98; mean age, 63 years; 57% men) or placebo (n=100; mean age, 63 years; 54% men).

Triglycerides decreased by 19.7% in patients assigned icosapent ethyl without increasing LDL compared with patients assigned placebo (P < .0001). This treatment also significantly improved other potentially inflammatory and atherogenic parameters.

At baseline and 12 weeks, respectively, serum creatinine was 0.9 and 0.9 mg/dL, eGFR was 75.4 and 79.1 mL/min/1.73 m², and albumin was 4.5 and 4.5 g/dL for icosapent ethyl 4 g per day. All percentage changes vs. placebo were not statistically significant.

EPA increased by 611.7% in red blood cells and by 676.2% in plasma in the icosapent ethyl group vs. placebo (P for both < .0001).

“At the present time, physicians should be aware of the data and understand the increased risk that their patients with reduced renal function and diabetes have,” Szerlip told Cardiology Today. “All necessary interventions to decrease their cardiovascular risk burden should be employed. These interventions include a healthy diet, exercise, weight reduction, smoking cessation, stringent BP control as per our new guidelines, statin use and blood sugar control.”

Triglycerides and high-sensitivity CRP

In a separate presentation, Vijayaraghavan and colleagues analyzed data from 152 patients from the ANCHOR trial with increased CVD risk who were treated with statins and had triglycerides between 200 mg/dL and 499 mg/dL even with LDL levels between 40 mg/dL and 99 mg/dL. Patients also had elevated high-sensitivity CRP greater than 2 mg/dL at baseline and an eGFR less than 90 mL/min/1.73 m² for more than 3 months.

In this analysis, 72 patients were assigned 4 g per day of icosapent ethyl (mean age, 63 years; 58% men) and 80 patients were assigned placebo (mean age, 64 years; 50% men).

Triglycerides decreased by 16.9% in patients assigned icosapent ethyl compared with those assigned placebo (P < .0001). This decrease did not affect LDL and resulted in an improvement in other potentially inflammatory or atherogenic parameters.

Icosapent ethyl 4 g per day did not produce significant changes from baseline to week 12 in serum creatinine, eGFR, albumin, or blood urea nitrogen. At baseline and 12 weeks, respectively, median serum creatinine was 0.9 and 0.9 mg/dL, median eGFR was 72.4 and 78.5 mL/min/1.73 m², median albumin was 4.5 and 4.4 g/dL, and median blood urea nitrogen was 18 and 18 mg/dL for icosapent ethyl 4 g per day. All percentage changes vs. placebo were not statistically significant.

Compared with placebo, icosapent ethyl increased EPA by 622% in red blood cells and by 662.7% in plasma (P for both < .0001).

“The clinical implications of these data are meaningful, so far as a health care provider would want to address the larger picture of stabilization of a vulnerable state of higher cardiovascular event risk in the [chronic kidney disease] population with increased inflammatory background,” Vijayaraghavan said in an interview. – by Darlene Dobkowski

References:

Szerlip HM, et al. Abstract 159.

Vijayaraghavan K, et al. Abstract 161. Both presented at: National Kidney Foundation Spring Clinical Meetings; April 10-14, 2018; Austin, Texas.

Disclosures: Szerlip reports he received consultant fees from Amarin. Vijayaraghavan reports he consults for Amarin.

Editor’s Note: This article was updated on April 26, 2018 to reflect updates to the data.