Icosapent ethyl shows consistent benefit in statin-treated patients regardless of eGFR status
16 Nov 2020
byAudrey Abella
The REDUCE-IT* RENAL study, a substudy of the REDUCE-IT trial, reflected the consistent benefit of icosapent ethyl (IPE) in statin-treated patients with established** cardiovascular disease (CVD) or diabetes, regardless of eGFR*** status.
“In REDUCE-IT RENAL, both primary# and secondary## endpoint event rates increased with decreasing eGFR. [Nonetheless,] relative risk reductions (RRRs) were similar with IPE vs placebo … across a broad range of eGFR categories,” said Dr Arjun Majithia from the Brigham & Women’s Hospital, Boston, Massachusetts, US, who presented the findings.
“Chronic kidney disease is associated with adverse outcomes amongst patients with established CVD or diabetes,” he noted. The findings thus underline the potential benefit of IPE in this setting, as “several widely available CV medications for the treatment of CVD [in] patients with low eGFR may be ineffective.”
Data on the >8,000 REDUCE-IT patients receiving either IPE 4 g daily or placebo were stratified into three eGFR categories: <60 mL/min/1.73 m2 (G3; n=1,816), 60–90 mL/min/1.73 m2 (G2; n=4,455), and ≥90 mL/min/1.73 m2 (G1; n=1,902). [ASN Kidney Week 2020, abstract FR-OR18]
Looking at the primary endpoint by baseline eGFR, the IPE benefit seen in the overall population (hazard ratio [HR], 0.75) appears to be sustained in each eGFR category (HRs, 0.71, 0.80, and 0.70 for G3, G2, and G1, respectively).
“[W]e observed early, consistent, and sustained separation in primary endpoint event rates,” said Majithia.
Notably, CV event rates with IPE were higher in the G3 vs the G2 and G1 arms (22 percent vs 17 percent [G2] and 13 percent [G1]). Absolute risk reduction (ARR) was greater in the G3 arm (7 percent vs 4 percent and 5 percent), but RRRs were similar across all eGFR categories (29, 20, and 30 percent for G3, G2, and G1, respectively). RRR in G3 was highly statistically significant (p=0.0002); p values for G2 and G1 were 0.001 and 0.003, respectively.
In a post hoc analysis further stratifying patients according to eGFR categories corresponding to CKD stage, there were consistent CV event reductions in IPE vs placebo recipients with eGFRs of ≥15 to <30, ≥30 to <45, and ≥45 to <60 mL/min/1.73 m2 (HRs, 0.59, 0.83, and 0.66, respectively). “[However,] the study was not specifically powered to identify differences within these categories,” said Majithia.
Regarding the key secondary endpoint, there was again a consistent, significant benefit across all eGFR categories with IPE vs placebo (HRs, 0.71, 0.77, and 0.70 for G3, G2, and G1, respectively), which mirrored that seen in the overall cohort (HR, 0.74). As in the primary endpoint, ischaemic CV event rates with IPE were higher in the G3 (17 percent) vs the G2 and G1 arms (10 percent and 8 percent, respectively). ARR was also higher in the G3 arm (6 percent vs 3 percent [both G2 and G1]); RRRs were similar across all categories (29, 23, and 30 percent, respectively). The corresponding p values for G3, G2, and G1 were 0.001, 0.002, and 0.02, respectively.
Post hoc analysis of the secondary endpoint also revealed consistent benefits with IPE including patients with the lowest eGFR category of 15–30, Majithia noted.
Looking at the prespecified hierarchical testing results, consistent benefits with IPE vs placebo were observed regarding CV death or nonfatal MI (HR, 0.75), fatal or nonfatal MI (HR, 0.69), and urgent or emergent revascularization (HR, 0.65).
“A safety profile similar to the full cohort was observed for IPE vs placebo across eGFR subgroups, including numerical/statistical increases in total bleeding events without statistical increases in serious central nervous system or gastrointestinal bleeding, and numerical increases in atrial fibrillation/flutter,” said Majithia.
Additionally, the incidence of microalbuminuria was lower with IPE vs placebo (n=3 vs 14). However, urine samples were not collected. “[We] relied on spontaneous checking/reporting. [As such,] microalbuminuria may have been underreported,” he said.