Table 2.
Anti-inflammatory and immune therapies in patients with established CAD.
| Drug | Principal Mechanism of Action | Study | Design | Population | Findings |
|---|---|---|---|---|---|
| Colchicine | Inhibition of microtubules polymerisation | COLCOT (NCT02551094) LoDoCo2 (ACTRN12614000093684) |
Phase III RCT | 4745 pts with recent MI (COLCOT) 5522 pts with chronic CAD (LoDoCo2) |
Colchicine 0.5 mg significantly reduced the risk of ischemic CV events [70,71] |
| Canakinumab | anti-IL-1β monoclonal antibody | CANTOS (NCT01327846) |
Phase III RCT | 10,061 pts with previous MI and hs-CRP >2 mg/L | Canakinumab 150 mg every 3 months significantly reduced the rate of recurrent CV events [69] |
| Methotrexate | Folate pathway antagonist | CIRT (NCT01594333) |
Phase III RCT | 4786 pts with previous MI or MVD | MTX 15–20 mg weekly did not reduce levels of IL-1β, IL-6, or CRP and did not reduce CV events [99]; a phase III RCT evaluating MTX delivered in LDL-nanoparticles is ongoing (NCT04616872) |
| Anakinra | Inhibition of the interaction between IL-1 and IL-1R | VCU-ART3 (NCT01950299) |
Phase II RCT | 99 pts with STEMI and acute HF | Anakinra significantly reduces the systemic inflammatory response after STEMI; no difference in terms of CV outcomes [100] |
| Tocilizumab | Inhibits IL-6R | ASSAIL-MI (NCT03004703) |
Phase II RCT | 199 pts with STEMI | Tocilizumab increased myocardial salvage; no difference in terms of CV outcomes [101] |
| Ziltivekimab | Inhibits IL-6 ligand | RESCUE (NCT03926117) |
Phase II RCT | 264 pts with CKD | Ziltivekimab reduced biomarkers of inflammation and thrombosis [102]; phase III RCT evaluating the effect on CV outcomes is ongoing (NCT05021835) |
CAD, coronary artery disease; CKD, chronic kidney disease; CRP, C-reactive protein; CV, cardiovascular events; HF, heart failure; hs-CRP, high-sensitivity C-reactive protein; IL-1, interleukin-1; IL-1R, interleukin-1 receptor; IL-1β, interleukin-1β; IL-6, interleukin-6; IL-6R, interleukin-6 receptor; LDL, low-density lipoprotein; MI, myocardial infarction; MTX, methotrexate; MVD, multivessel disease; STEMI, ST-elevation myocardial infarction; pts, patients; RCT, randomized controlled trials.