Key Points:
- In the original CANTOS, patients with stable CAD post-MI with elevated CRP were randomized to either canakinumab or placebo. In this secondary analysis, , the relative contributions of residual cholesterol risk and residual inflammatory risk were determined in the prediction of MACE, CV death, and mortality in patients already treated with statins, which was then stratified by eGFR.
- Elevated levels of both hsCRP and IL-6 were found to be predictive of MACE in patients with both preserved and reduced kidney function; however, LDLC and non-HDLC were predictive of MACE only in preserved kidney function. Elevated CRP predicted CV mortality, with or without kidney dysfunction.
- Residual inflammatory risk appears to play an important role in determining MACE risk in patients already treated with lipid-lowering therapy.
Inflammation has recently been identified as an independent contributor to the development of atherosclerotic cardiovascular disease, and it has also been theorized to act jointly with hyperlipidemia in the development of this risk. Canakinumab is a monoclonal antibody which neutralizes IL-1β and was recently studied in the CANTOS trial to determine whether it could effect MACE reduction in patients with stable CAD post MI and elevated CRP. In a breaking presentation at the 2022 American College of Cardiology Conference today, Dr. Paul Ridker (Brigham and Women’s Hospital, Boston) and his team presented “Residual Inflammatory Risk and Residual Cholesterol Risk Among Statin Treated Atherosclerosis Patients With and Without Chronic Kidney Disease: A Secondary Analysis of CANTOS.”
The original CANTOS study (NCT01327846) was a randomized multicenter trial which demonstrated that patients with stable CAD post MI and elevated CRP (≥2mg/L) led to reduced MACE at a median follow-up of 3.7 years. In this secondary analysis, the relative contributions of residual cholesterol risk and residual inflammatory risk were determined in the prediction of MACE, CV death, and mortality, which was then stratified by eGFR.
A total of 9,151 randomized patients (all of whom were treated with statins) were analyzed and followed for up to 5 years. hsCRP, IL-6, LDLC, and non-HDLC were measured and monitored. For the primary outcome, hsCRP and IL-6 were both found to be predictive of MACE in patients with both preserved and reduced kidney function; however, LDLC and non-HDLC were predictive of MACE only in preserved kidney function. Elevated CRP predicted CV mortality, with or without the concomitant presence of kidney dysfunction.
When discussing the additive potential of anti-inflammatory therapies to existing medical therapy for CAD at the ACC, Dr. Ridker stated: “Relative risk reduction is infinite…there is a lot of residual risk in these [stable CAD] patients…upcoming trials of anti-inflammatory drugs will be in addition to standard of care therapies for CAD [such as SGLT2s].”