Table 2.

Major randomized clinical trials of anti-inflammatory therapy in cardiovascular disease

Trial	Inclusion criteria	Intervention	Signaling pathway	Size	Results	Benefit observed
Anti-inflammatory Therapy with Cankinumab for Atherosclerosis (CANTOS) [6]	Previous MI and a hs-CRP ≥ 2 mg/l	Canakinumab (subcutaneous injection 50 mg, 150 mg or 300 mg every 3 months) vs placebo	Interleukin-1ß	N = 10,061	HR 0.85; 95% CI 0.74–0.98; p = 0.021 in the 150 mg treated group	Yes
Cardiovascular Inflammation Reduction Trial (CIRT) [86]	Previous MI; MVD with DM2/metabolic syndrome	Methotrexate (15–20 mg weekly) vs placebo	Interleukin-6, TNF	N = 4786	HR 1.01; 95% CI 0.82–1.25; p = 0.91	No
Colchicine Cardiovascular Outcomes Trial (COLCOT) [87]	Previous MI ≤ 30 days	Colchicine (0.5 mg daily) vs placebo	Multiple targets	N = 4745	HR 0.33; 95% CI 0.18–0.59; p < 0.001 HR 0.77; 95% CI 0.61–0.96; p = 0.02	Yes
Low Dose Colchicine (LoDoCo2) [88]	Chronic coronary syndrome	Colchicine (0.5 mg daily) vs placebo	Multiple targets	N = 5522	HR 0.69; 95% CI 0.57–0.83; p < 0.001 HR 0.72; 95% CI 0.57–0.92; p = 0.007	Yes
SOLID-TIMI 52 [89]	Previous MI	Darapladib (160 mg daily) vs placebo	Lipoprotein-Phospholipase A2	N = 13,026	HR 1.00; 95% CI 0.91–1.09; p = 0.93	No
LATITUDE-TIMI 60 [90]	Acute MI	Losmapimod (7.5 mg twice daily) vs placebo	P38 mitogen-activated protein kinases	N = 3503	HR 1.16; 95% CI 0.91–1.47; p = 0.24	No
Aggressive Reduction of Inflammation Stops Events (ARISE) [91]	Previous ACS	Succinobucol (300 mg daily) vs placebo	LDL-Oxidation	N = 6144	HR 1.00, 95% CI 0.89–1.13, p = 0.96	No
VISTA-16 [92]	ACS	Varespladib (500 mg daily) vs placebo	Secretory Phospholipase A2	N = 5000	HR 1.25; 95% CI 0.97–1.61; p = 0.08	No

ACS acute coronary syndrome, HR hazard ratio, CI confidence interval, LDL low density lipoprotein, MI myocardial infarction, hsCRP high-sensitivity C-reactive protein, MVD multivessel coronary disease, DM2 type 2 diabetes mellitus