ARTICLE: Treatment concentration of high-sensitivity C-reactive protein
AUTHORS: Erin D. Michos, Roger S. Blumenthal
JOURNAL: Lancet. 2017 Nov 13. pii: S0140-6736(17)32865-9. doi: 10.1016/S0140-6736(17)32865-9. [Epub ahead of print]
The landmark CANTOS trial evaluated the use of canakinumab, a monoclonal antibodytargeting interleukin 1β, in 10 061 patients with previous myocardial infarction who had high-sensitivity C-reactive protein (hsCRP) concentrations of 2 mg/L or higher.1 Interleukin 1β has multiple potential mechanisms that contribute to the pathogenesis of atherothrombotic cardiovascular disease.2 Induction of interleukin 6 leads to the release of acute phase reactants including hsCRP. Thus, hsCRP serves as a surrogate marker of the overall inflammatory milieu,2 often in situations where patients have multiple co-morbidities,3 with a cumulative dose-response indicating a higher risk.4
CANTOS propelled the prevention field forward by showing that the inflammation-targeted therapy canakinumab (at 50, 150, or 300 mg subcutaneously once every 3 months) conferred a relative 15% reduction in major adverse cardiovascular events over a median of 3·7 years without altering the lipid profile.1 Interestingly, there was also a significant 30% reduction in fatal cancer, balanced by a modest increase in fatal infection, with no difference in all-cause mortality. Thus, the observed reduction in the primary endpoint likely would not justify its routine use in all patients post myocardial infarction with elevated hsCRP.
So which patients, pending regulatory approval, might we consider canakinumab for? In The Lancet, Paul Ridker and colleagues5 report that baseline demographics did not identify which groups of patients post myocardial infarction are most likely to benefit. Although women only made up 25% of the CANTOS sample and generally have higher baseline hsCRP relative to men,6 they derived the same benefit. Individuals with lower LDL cholesterol are generally at lower risk for recurrent major adverse cardiovascular events, but they also equally benefited with canakinumab. Younger adults, individuals without diabetes, non-smokers, and the non-obese also equally benefited.
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