From joints to vessels: How rheumatoid arthritis therapy alters the fate of the heart

Table 3 Comparison of CANTOS and CIRT trials: Impact of anti-inflammatory therapy on cardiovascular outcomes

Criterion	CANTOS (2017)	CIRT (2019)
Study drug	Canakinumab (IL-1β inhibitor)	Methotrexate
Study objective	Evaluate IL-1β suppression on cardiovascular outcomes	Test if low-dose immunosuppression reduces CVD risk
Design	Double-blind, placebo-controlled, multicenter	Double-blind, placebo-controlled, multicenter
Patient population	10061 patients with CAD and hs-CRP ≥ 2 mg/L	4786 patients with CAD/metabolic syndrome + diabetes/obesity
Primary outcomes	15% reduction in acute coronary syndrome (MI, unstable angina, cardiac death) (P = 0.007)	No significant effect: No difference in CVD outcomes vs placebo (P = 0.67)
	37%-41% reduction in hs-CRP
Effect on inflammation	Sustained reduction in IL-6 and hs-CRP	Minimal impact on CRP
Adverse effects	↑ Fatal infections (0.18 vs 0.06 per 100 person-years)	↑ Liver enzyme abnormalities
	↑ LDL levels	↑ Leukopenia risk
Conclusions	Hypothesis confirmed: IL-1β is a valid target for secondary CVD prevention	Hypothesis rejected: Methotrexate does not reduce CVD risk in this population

IL-1β: Interleukin-1β; hs-CRP: High-sensitivity C-reactive protein; CAD: Coronary artery disease; MI: Myocardial infarction; CVD: Cardiovascular disease; LDL: Low-density lipoprotein.