Physicians' Academy for Cardiovascular Education

Inflammation stronger predictor of future MACE in statin-treated CKD patients than LDL-c

Inflammation drives residual risk in chronic kidney disease: a CANTOS substudy

Literature - Ridker PM, Tuttle KR, Perkovic V, et al. - Eur Heart J. 2022 Aug 9;ehac444 [Online ahead of print]. doi: 10.1093/eurheartj/ehac444

Introduction and methods


Despite taking statins, patients with atherosclerosis and CKD have a particularly high risk of recurrent CV events. However, it is not clear what drives the occurrence of MACE in this population: their residual cholesterol risk or their residual inflammatory risk?

Aim of the study

The authors set out to evaluate the relative utility of lipid and inflammatory biomarker levels as predictors of future MACE, CV death, and all-cause mortality in stable atherosclerosis patients on statin therapy who had participated in the CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) trial, stratified by eGFR.


In the international CANTOS trial, the effect of IL -1β inhibition with canakinumab versus placebo was investigated in stable coronary artery disease [1]. For the current substudy, data from 9151 statin-treated patients with a history of MI, and hs-CRP >2 mg/L and eGFR >30 mL/min per 1.73 m2 at baseline were used. Irrespective of randomized treatment allocation, participants were divided into two groups based on baseline eGFR (recalculated using the race agnostic CKD-EPI 2021 formula): <60 versus ≥60 mL/min per 1.73 m2. The median follow-up duration was 3.7 years.

The primary analyses focused on LDL-c and hs-CRP, whereas the secondary analyses focused on non–HDL-c and IL-6. In additional secondary analyses, participants were stratified by albumin-to-creatinine ratio (<3 vs. ≥3 mg/mmol), rather than by eGFR. All analyses were adjusted for randomized treatment assignment. To eliminate potential confounding based on treatment allocation, additional sensitivity analyses were performed in patients in the placebo group.


The endpoints were adjudicated incident CV clinical outcomes (including recurrent nonfatal MI, nonfatal stroke, coronary revascularization procedures, and CV death) and adjudicated all-cause mortality.

Main results

MACE risk

CV death risk

All-cause mortality risk

Stratification by albumin-to-creatinine ratio


In statin-treated, post-MI patients with preserved kidney function, both residual inflammatory risk (as assessed by hs-CRP or IL-6) and residual cholesterol risk (as assessed by LDL-c or non–HDL-c) were associated with risk of MACE. However, in those with impaired kidney function, only residual inflammatory risk predicted MACE. The authors believe their results have implications for CV risk stratification of CKD patients and for the development of novel therapeutic agents that target inflammatory processes in this high-risk patient group.


Show references

Find this article online at Eur Heart J.

Share this page with your colleagues and friends: