Icosapent ethyl reduces atherogenic markers in high-risk statin-treated patients with stage 3 chronic kidney disease and high triglycerides

Figures & data

Table 1. Baseline Characteristics (CKD Subset of ANCHOR ITT Population).

Variable	Icosapent Ethyl 4 g/day (n = 18)	Icosapent Ethyl 2 g/day (n = 30)	Placebo (n = 35)
Age, mean (SD), years	68.2 (7.2)	67.9 (8.3)	68.0 (8.4)
Sex, n (%)
Male	10 (55.6)	15 (50.0)	17 (48.6)
Female	8 (44.4)	15 (50.0)	18 (51.4)
Race, n (%)
White	18 (100)	28 (93.3)	34 (97.1)
Body mass index, mean (SD), kg/m^2	32.2 (4.8)	31.8 (5.5)	33.4 (5.5)
eGFR
Mean (SD), mL/min/1.73 m^2	50.5 (10.6)	49.8 (7.2)	50.3 (7.3)
Median (minimum, maximum)	55.0 (24.7, 59.7)	50.5 (34.3, 59.4)	52.4 (32.7, 59.6)
Diabetes, n (%)	10 (55.6)	24 (80.0)	24 (68.6)

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; ITT, intent-to-treat; SD, standard deviation.

Table 2. Effects of Icosapent Ethyl on Lipids/Lipoproteins, Apolipoproteins, ox-LDL, hsCRP, and Lp-PLA₂ (CKD Subset of ANCHOR ITT Population).

										Median Difference in % Change From Baseline vs Placebo
Parameter	Icosapent Ethyl 4 g/day			Icosapent Ethyl 2 g/day			Placebo			Icosapent Ethyl 4 g/day	Icosapent Ethyl 2 g/day
	Baseline	End of Treatment	Change, %	Baseline	End of Treatment	Change, %	Baseline	End of Treatment	Change, %	%, P Value	%, P Value
Lipids/Lipoproteins
TG (mg/dL) (primary efficacy variable)
n = 18, 30, 35	268.5	230.5	–17.1	268.0	247.8	–7.8	262.0	272.5	5.9	–16.9	–11.7
	(101.5)	(66.0)	(43.2)	(112.0)	(130.0)	(30.0)	(70.5)	(98.5)	(36.0)	0.0074	0.0523
LDL-C (mg/dL)
n = 18, 30, 35	76.0	70.5	–6.5	80.5	87.5	–0.7	74.0	84.0	13.7	–20.8	–12.1
	(24.0)	(24.0)	(19.9)	(18.0)	(27.0)	(24.6)	(38.0)	(27.0)	(38.9)	0.0086	0.0539
Non-HDL-C (mg/dL)
n = 18, 30, 35	124.5	116.0	–8.4	129.0	137.5	0.9	131.0	141.0	10.7	–21.5	–9.3
	(34.0)	(21.0)	(7.7)	(36.00)	(38.0)	(25.8)	(31.0)	(45.0)	(34.3)	<0.0001	0.0947
TC (mg/dL)
n = 18, 30, 35	159.5	151.5	–8.1	177.0	178.5	1.5	165.0	176.0	9.5	–18.2	–8.0
	(49.0)	(41.0)	(8.2)	(38.0)	(41.0)	(20.3)	(43.0)	(40.0)	(21.0)	<0.0001	0.0395
HDL-C (mg/dL)
n = 18, 30, 35	35.0	35.5	0.9	37.5	39.0	0.0	40.0	40.0	10.4	–8.3	–5.6
	(13.0)	(14.0)	(12.4)	(12.0)	(16.0)	(17.22)	(15.0)	(21.0)	(25.0)	0.0362	0.2088
VLDL-C (mg/dL)
n = 18, 30, 35	42.0	36.5	–16.3	45.0	48.0	5.0	47.0	55.0	10.0	–28.7	–7.3
	(12.0)	(12.0)	(40.4)	(30.0)	(22.0)	(48.8)	(19.0)	(20.0)	(46.0)	0.0026	0.4108
VLDL-TG (mg/dL)
n = 18, 30, 35	194.0	168.5	–25.8	191.0	175.0	7.3	185.0	209.0	0.0	–25.6	–10.1
	(102.0)	(65.0)	(56.6)	(91.0)	(106.0)	(50.7)	(89.0)	(115.0)	(59.7)	0.0020	0.3887
RLP-C (mg/dL)*
n = 9, 11, 14	17.0	10.0	–38.9	12.0	11.0	–8.3	14.5	14.0	6.3	–38.8	–12.8
	(7.0)	(2.0)	(40.6)	(10.0)	(9.0)	(56.4)	(7.0)	(6.0)	(62.4)	0.0295	0.3956
Apolipoproteins
Apo B (mg/dL)^†
n = 17, 28, 35	87.0	83.0	–7.2	97.0	97.0	–1.6	90.0	94.0	13.0	–18.7	–9.8
	(27.0)	(22.0)	(10.2)	(15.5)	(22.0)	(18.8)	(22.0)	(24.0)	(23.3)	0.0002	0.0225
Apo C-III (mg/dL)^†
n = 13, 27, 32	15.6	13.9	–7.3	17.0	17.5	6.5	16.2	17.0	10.0	–15.0	–9.9
	(3.9)	(2.6)	(24.4)	(4.5)	(4.8)	(29.7)	(3.2)	(4.0)	(23.1)	0.0168	0.1549
Oxidation and Inflammation Markers
Ox-LDL (U/L)*
n = 8, 12, 17	48.6	45.1	–9.5	52.4	52.0	–1.8	53.7	55.5	16.7	–25.7	–15.0
	(19.7)	(21.6)	(8.6)	(6.5)	(21.2)	(19.50)	(10.5)	(21.6)	(31.6)	0.0068	0.1501
Lp-PLA2 (ng/mL)
n = 17, 28, 34	173.0	150.0	–12.7	186.5	176.5	–2.2	197.0	202.5	7.0	–17.5	–8.9
	(65.0)	(68.0)	(21.2)	(75.0)	(39.5)	(21.6)	(68.0)	(74.0)	(21.5)	0.0068	0.0782
hsCRP (mg/L)
n = 17, 28, 35	1.9	2.1	–16.9	2.5	2.3	11.0	2.6	2.6	9.1	–25.0	–19.6
	(1.8)	(2.9)	(26.1)	(4.9)	(2.9)	(76.0)	(3.8)	(6.3)	(103.3)	0.1209	0.3434

Data are presented as median (interquartile range) for endpoint values. Median percent changes versus placebo are Hodges-Lehmann estimates. P values from the Wilcoxon rank-sum test for treatment comparisons.

Patient numbers are presented as icosapent ethyl 4 g/day, 2 g/day, and placebo, respectively.

*RLP-C and ox-LDL were only measured in approximately the first 35% of patients randomized in ANCHOR.

^†Apo B and Apo C-III levels were measured in the subset of all patients with available archived plasma samples from ANCHOR.

Apo C-III, apolipoprotein C-III; Apo B, apolipoprotein B; HDL-C, high-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; LDL-C, low-density lipoprotein cholesterol; Lp-PLA₂, lipoprotein-associated phospholipase A₂; ox-LDL, oxidized low-density lipoprotein; RLP-C, remnant lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; VLDL-C, very-low-density lipoprotein cholesterol; VLDL-TG, very-low-density lipoprotein triglycerides.

Figure 1. Percent change in lipids/lipoproteins, apolipoproteins, ox-LDL, hsCRP, and Lp-PLA₂ in patients with CKD (CKD subset of ANCHOR ITT population). Values represent median difference in percent change from baseline to week 12 for (a) icosapent ethyl 4 g/day vs placebo and (b) icosapent ethyl 2 g/day vs placebo. IQRs are available for each parameter in Table 2. *P < 0.0001; ^†P < 0.001; ^‡P < 0.01; ^§P < 0.05; NS, not significant versus placebo. Apo C-III, apolipoprotein C-III; Apo B, apolipoprotein B; HDL-C, high-density lipoprotein cholesterol; non-HDL-C, non-high-density lipoprotein cholesterol; hsCRP, high-sensitivity C-reactive protein; IQR, interquartile range; LDL-C, low-density lipoprotein cholesterol; ox-LDL, oxidized low-density lipoprotein; RLP-C, remnant lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; VLDL-C, very-low-density lipoprotein cholesterol; VLDL-TG, very-low-density lipoprotein triglycerides.