Table 1.
Clinical trials of anti-inflammatory therapy for cardiovascular protection with positive outcomes.
| Clinical trial | Treatment | Target and mechanism | Patients | Outcomes | Reference |
|---|---|---|---|---|---|
| Cardiovascular protection in rheumatoid arthritis | |||||
| NCT01566201 | Anakinra | IL-1R | Rheumatoid arthritis | Improvement in endothelial, coronary aortic function and left ventricular myocardial deformation and twisting after CAD | (33) |
| ENTRACTE | Etanercept | TNF-α | Rheumatoid arthritis | Rare cardiovascular events in both groups. | Preliminary results (34) |
| Tocilizumab | IL-6 | ||||
| Coronary artery disease | |||||
| CANTOS | Canakinumab | IL-1β | Previous MI and hsCRP≥2 mg | Lower rate of nonfatal MI, nonfatal stroke, cardiovascular death, and hospitalized UA leading to urgent revascularization | (35) |
| LoDoCo | Colchicine | Central pathway* | SCAD | Prevention of ACS, out-of-hospital cardiac arrest, and non-cardioembolic ischemic stroke | (36) |
| COLCOT | Colchicine | Central pathway* | Within 30 days after a MI | Lower risk of cardiovascular death, resuscitated cardiac arrest, MI, stroke, and hospitalized UA leading to urgent revascularization) | (37) |
| Myocardial ischemia/reperfusion injury | |||||
| NCT01491074 | Tocilizumab | IL-6 | NSTEMI | Attenuated hsCRP and primarily PCI-related hsTnT release | (38) |
| Heart failure | |||||
| CANTOS | Canakinumab | IL-1β | Previous MI and hsCRP≥2 mg | Dose-dependent reduction in HHF and the composite of HHF or HF–related mortality | (39) |
| ACCLAIM | Immunomodulation therapy | Macrophages | NYHA II-IV chronic HF | Reduction in all-cause mortality and cardiovascular admission in patients with no history of MI or with NYHA II HF, | (40) |
| STAR-heart | Intracoronary bone marrow cell therapy | Resident cardiac macrophages# | Chronic HF due to ischemic cardiomyopathy | Improvement in ventricular performance, quality of life and survival | (41) |
| ixCELL-DCM | Ixmyelocel-T§ | Bone marrow mononuclear cells¶ | NYHA III or IV symptomatic HF due to ischemic dilated cardiomyopathy | Improvement in all-cause mortality, cardiac admissions, HF admissions, and left ventricular function | (42) |
| Chronic myocarditis/dilated cardiomyopathy | |||||
| CZECH-ICIT | Steroids and azathioprine | T cells suppression | Dilated cardiomyopathy and increased HLA expression on biopsy specimens | Long-term benefit in LVEF, LVV, LVDd, and NYHA class | (43) |
| TIMIC | Steroids and azathioprine | T cells suppression | Virus-negative myocarditis with chronic HF | Improvement in LVEF, LVV, LVD, and NYHA class | (44) |
Central pathway refers to the immune pathway linking IL-1β, TNF-α, and IL-6.
Patients' own blood was stressed to induced cell death, and then the mixture of apoptotic cells was injected intramuscularly into the same patient.
Macrophages that phagocytose apoptotic cells downregulate proinflammatory cytokines and upregulate anti-inflammatory cytokines.
Stem cells were taken up by resident cardiac macrophages which would exert cardioprotective effects.
Intramyocardial injection of expanded bone marrow–derived mesenchymal stem cells with macrophages activated ex vivo.
Bone marrow mononuclear cells express the anti-inflammatory cytokine IL-10 to exert protective role by limiting T-cell recruitment.
IL-1R, interleukin-1 receptor; CAD, coronary artery disease; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; IL-1β, interleukin-1β; MI, myocardial infarction; hsCRP, high-sensitivity C-reactive protein; UA, unstable angina; SCAD, stable coronary artery disease; ACS, acute coronary syndrome; NSTEMI, non-ST segment elevation myocardial infarction; PCI, percutaneous coronary intervention; hsTnT, high-sensitivity troponin T; HHF, hospitalization for heart failure; HF, heart failure; NYHA, New York Heart Association; IL-10, interleukin-10; HLA, human leukocyte antigen; LVEF, left ventricular ejection fraction; LVV, left ventricular volume; LVDd, left ventricular diastolic dimension.