Canakinumab (an IL-B inhibitor) is associated with decreased heart failure (HF) hospitalizations and the composite of heart failure hospitalization and heart-failure related mortality in patients with a history of myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hsCRP), according to a new study published in Circulation.
“The results presented here are exploratory and hypothesis-generating, but nonetheless represent the first large-scale evidence indicating that IL-1 targeted therapy may have a role in preventing hospitalization for heart failure and heart-failure related mortality.” – Everett et al.
10,061 MI patients with high levels of hsCRP (more than or equal to ≥2 mg/L) were randomized to receive either placebo, canakinumab 50 mg, 150 mg, or 300 mg subcutaneously every three months. There was no significant difference between any single dose of canakinumab and placebo. However, the trend across the three doses was significant for the reduction of HF hospitalization (P-trend = 0.025) and the composite of heart failure hospitalization and heart-failure related mortality (P-trend = 0.037). The authors commented, “This study represents the first time a targeted anti-inflammatory therapy has reduced hospitalization for heart failure in at-risk patients with a history of myocardial infarction and ongoing subclinical inflammation.”
Targetting a new mechanism to help MI patients?
It is already known that certain inflammatory markers such as IL-6 and CRP are predictive of death and the exercise capacity of heart failure patients. However, previous randomized clinical trials on etanercept and infliximab [tumor necrotizing factor (TNF) inhibitors] did not show decreased mortality risk in HF patients.
The study also showed that the baseline concentrations of IL-6 and hsCRP were correlated with the risk of HF hospitalization. Additionally, patients who achieved a concentration of hsCRP <2 mg/L while on treatment had a lower risk of the endpoints of the study which was one more proof that the anti-inflammatory characteristics of the drug explained the findings of the study. Another important finding was that canakinumab did not cause significant changes in the blood pressure or the renal function of the patients. The patient population of the study had a high rate of using beta blockers and drugs affecting the renin-angiotensin-aldosterone system. Indeed, the absence of a drug interaction with these drugs by targeting a new mechanism was beneficial. The authors concluded, “The results presented here are exploratory and hypothesis-generating, but nonetheless represent the first large-scale evidence indicating that IL-1 targeted therapy may have a role in preventing hospitalization for heart failure and heart-failure related mortality.”
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