Does Magnitude of CRP Level Reduction Correlate With Cardiovascular Mortality?

In a recent study published in The Lancet, it has been found that the magnitude of reduction in C Reactive Protein (CRP) levels due to treatment with Canakinumab, an interleukin 1β targeting monoclonal antibody, may directly correlate with a decrease in major cardiovascular events in post-myocardial infarction (MI) patients, even in the absence of an alteration in LDL levels.

Previous studies have shown that Canakinumab decreases inflammation and cardiovascular mortality without altering lipid levels. However, the correlation of reduced CRP levels and cardiovascular event reduction was yet to be determined. To address this, Ridker and his colleagues recently published the results of a secondary analysis of the CANTOS trial in The Lancet.

A total of 10,061 stable patients with a history of MI were enrolled in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) and treated with placebo or one of three doses of Canakinumab (50, 150 or 300mg) administered subcutaneously every three months.  The primary endpoint of the study was a composite of major adverse cardiovascular events including cardiovascular death, stroke and recurrent MI. Additional endpoints encompassed hospitalization for unstable angina, all-cause, and cardiovascular mortality.  The median follow-up period was 3.7 years.

Ridker et al reported that a CRP level of less than 2mg/L led to a 25 percent reduction in major adverse cardiovascular events. Cardiovascular and all-cause mortality in these patients were both reduced by 31 percent. These findings clearly showcased a relationship between the degree of reduction in serum CRP levels and a decrease in cardiovascular events in patients treated with Canakinumab.

The authors acknowledge the limitations of the study by stating that, “the observations made here are no longer formally randomized.” They remind us that their data only applies to Canakinumab and “those with elevated CRP at study entry.” However, Ridker and his colleagues argue that “for individual patients where variability in drug response might exist, the availability of both a 150 mg and a 300 mg dose might broaden the clinical use of Canakinumab.”

This study helps demarcate the difference in treatment approach between patients having a residual risk of inflammation as opposed to those with residual cholesterol risk. “We believe the clinical approach of targeting treatment to those who truly benefit on the basis of biological response represents a major step toward personalized medicine and rational resource utilization.”