Table 1.
Main clinical randomized, placebo-controlled, double-blind trials that investigated anti-inflammatory drugs to reduce atherosclerotic cardiovascular risk.
| Trial | Tested Drug | Mechanism of Action | Study Design | N Patients | Study Population | Follow-Up Duration | Main Findings |
|---|---|---|---|---|---|---|---|
| CANTOS [47] | Canakinumab | IL-1β inhibition | Randomized Controlled Double-blind Phase 3 Trial |
10,061 | Previous MI and high CRP levels |
3.7 years * | Canakinumab reduced cardiovascular events |
| COLCOT [50] | Colchicine | Tubulin polymerization and inflammasome inhibition | Randomized Controlled Double-blind Phase 3 Trial | 4745 | Patients who had had a MI within 30 days before recruitment |
22.6 months * | Significant reduction in ischemic cardiovascular events |
| LoDoCo2 [51] | Colchicine | Tubulin polymerization and inflammasome inhibition | Randomized Controlled Double-blind Phase 3 Trial |
5522 | Chronic coronary disease | 28.6 months * | Colchicine vs. placebo reduced cardiovascular event risk |
| VCUART3 [53] | Anakinra | IL-1 receptor antagonist | Randomized Controlled Double-blind Phase 2 Trial |
99 | ST-segment-elevation myocardial infarction | 12 months | Significant reduction in hsCRP area under the curve during the first 14 days. Lower incidence of HF. |
| RESCUE [54] | Ziltivekimab | IL-6 inhibition | Randomized Controlled Double-blind Phase 2 Trial |
264 | Chronic kidney disease and high CRP levels |
24 weeks | Ziltivekimab (dose dependent) reduced inflammation and thrombosis biomarkers |
| Tocilizumab in NSTEMI patients (ClinicalTrials.gov, NCT01491074) [55] |
Tocilizumab | IL-6 receptor inhibition | Randomized Controlled Double-blind Phase 2 trial |
117 | NSTEMI patients scheduled for angiography | 6 months | Tocilizumab reduced hsCRP levels and troponin T release after PCI |
| ASSAIL-MI [56] | Tocilizumab | IL-6 receptor inhibition | Randomized Controlled Double-blind Phase 2 trial |
199 | STEMI patients within 6 h of symptom onset | 6 months | Greater myocardial salvage index (Measured with CMR after 3–6 days) |
| CIRT [38] | Metothrexate | Nucleotide synthesis inhibition leading to suppression of inflammation | Randomized Controlled Double-blind Phase 3 Trial |
4786 | Previous MI or multivessel CAD and Type 2 diabetes or metabolic syndrome |
2.3 years * | Low-dose methotrexate did not result in lower IL-1B/ IL-6 or CRP levels |
* Median. CAD indicates coronary artery disease; CMR, cardiac magnetic resonance; CRP, C-reactive protein; HF, heart failure; IL, interleukin; MI, myocardial infarction; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction.