Table 4.
Study characteristics of clinical trials using cytokine inhibition
| Study | Design | n | Study population (% ischaemia) | Intervention | Dose/administration | Follow-up | Outcome measures |
|---|---|---|---|---|---|---|---|
| IL-1 inhibitors | |||||||
| Ridker et al.78 (CANTOS) | R, DB, PC | 10 061 | Previous MI | Canakinumab | 150 OR 200 OR 300 mg | 3.7 years | Mortality (0); MACE (+); SAE (−); CRP (+); LDL (0). |
| Van Tassell et al.79 | R, DB, PC | 30 | HF (33.3%) | Anakinra | 100 mg twice daily for 3 days + daily for 11 days | 2 weeks | MACE (0); clinical cardiac exam (0); LVEF (+); CRP (+); IL-6 (+); IL17 (0); lpPLA2 (0); Leptin (0); MPO (+); NTpro-BNP (0); galectin 3 (0); TNFa (0); hs-TnI (+). |
| Morton et al.80 (MRC-ILA Heart Study) | R, DB, PC | 182 | ACS (26%) | Anakinra | 100 mg sc once only | 1 year | Mortality (0); MACE (−); hs-CRP (+); FBC (0); IL-6 (+); platelets (+); TnT (0) TnI (0); WCC (+). |
| Sonnino et al.81 | R, DB, PC. ex vivo | 17 | AMI | Anakinra | 100 mg | 3 months | IL6 (+). |
| Abbate et al.82 (VCU-ART) | R, DB, PC | 10 | AMI | Anakinra | 100 mg sc daily for 2 weeks | 3.5 months | CI (+); LVEDV (+); LVEF (0); LVESVi (+); CRP (+). |
| Ridker et al.83 | R, DB, PC | 556 | T2DM with high-MI risk | Canakinumab | 5 OR 15 OR 50 OR 150 mg | 4 months | CRP (+); fibrinogen (+); HbA1c (0); IL-6 (+); triglyceride (−). |
| IL-6 inhibitors | |||||||
| Holte et al.84 | R, DB, PC | 117 | NSTEMI | Tocilizumab | 280 mg IV | 6 months | Coronary flow reserve (0); VCAM-1 (+) |
| Kleveland et al.85 | R, DB, PC | 117 | NSTEMI | Tocilizumab | 280 mg IV | 6 months | LVEF (0); SAE (0); nt-proBNP (0); Hb (0); hs-CRP (+); leukocytes (+); lipids (0); platelets (0); hs-TnT (+). |
| Carroll et al.86 | R, DB, PC | 28 | MI | Tocilizumab | 162 mg sc | 1 month | MACE (0); CRP (0); ECG (0). |
| TNF inhibitors | |||||||
| Padfield et al.87 | R, DB, PC | 26 | MI | Etanercept | 10 mg IV | 24 h | IL-6 (+); neutrophil (+); platelet-monocyte aggregate (−); t-PA (0). |
| Mann et al.88 (RENAISSANCE) | R, DB, PC | 1123 | CHF (16.3%) | Etanercept | 25 mg sc BIW OR TIW | 24 weeks | Mortality (0); MACE (0). |
| Mann et al.89 (RECOVER) | R, DB, PC | 925 | CHF (20%) | Etanercept | 25 mg sc QW OR BIW | 5.5 months | Mortality (0); MACE (0); |
| Chung et al.90 (ATTACH) | R, DB, PC | 150 | CHF | Infliximab | 5 or 10 mg/kg | 28 weeks | Clinical composite score (0), LVEF (0), CRP (+), IL-6 (+), worsened heart failure (+), mortality (+) |
| Bozkurt et al.91 | R, DB, PC | 47 | HF (82%) | Etanercept | 5 mg/m2 OR 12 mg/m2 sc BIW for 3 months | 3 months | Adverse events; functional status (0); LVEF (+); LVESV (+); LVEDV (+); LVESV (+) LV mass (0). |
| Fichtlscherer et al.92 | ND, OL, NPC | 18 | HF (50%) | Etanercept | 25 mg sc QW | 7 days | Endothelium dependent forearm blood flow (+); endothelium independent flow (0) |
| Deswal et al.93 | R, DB, PC | 18 | HF (83%) | Etanercept | 1, 4, 10 mg/m2 | 2 weeks | EF (+); 6MWT (+), QOL scores (+). |
ACS, acute coronary syndrome; T2DM, Type 2 diabetes mellitus; NSTEMI, non-ST elevation myocardial infarction; sc, subcutaneous injection; BIW, twice weekly; TIW, three times a week; QW, once weekly; IpPLA2, lipoprotein-associated phospholipase A2; MPO, myeloperoxidase; Ntpro-BNP, N-terminal pro b-type natriuretic peptide; TnI/T, troponin I/T; FBC, full blood count; WCC, white cell count; LVESVi, left ventricular end-systolic volume index; HbA1c, haemoglobin A1c; VCAM-1, vascular cell adhesion protein 1; Hb, haemoglobin; SAE, serious adverse events; t-PA, tissue plasminogen activator; EF, ejection fraction; R, randomized; DB, double blind; PC, placebo controlled; MACE, major adverse cardiac event; hs-CRP, high-sensitivity C-reactive protein; LVEF, left ventricular ejection fraction; TNF, tumour necrosis factor; ECG, electrocardiogram; (+), supports intervention use; (−), supports placebo use; (0), no difference between intervention and placebo; 6MWT, 6 min walk test; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume.