Table 1.
Summary of major clinical trials targeting inflammatory pathways and immune-modulatory therapies in heart failure
| Study | Treatment | Target | Duration (months) | Clinical setting | NYHA class | n | Primary outcome |
|---|---|---|---|---|---|---|---|
| ATTACH [66] | Infliximab | TNFα | 7 | DCM, ICM | III, IV | 150 | ↑ Death and hospitalization for HF at high doses |
| RENEWAL (RECOVER and RENAISSANCE) [67] | Etanercept | TNFα | 5.7/12.9 | DCM, ICM | II–IV | 2048 | ↔ Death and hospitalization rate for HF |
| Gullestad et al. [69] | Thalidomide | Multiple | 3 | DCM, ICM | II, III | 56 | ↑ LVEF |
| Parrillo et al. [81] | Prednisone | Multiple | 3 | DCM | – | 102 | ↑ LVEF |
| Skudicky et al. [70] | Pentoxifylline | Multiple | 6 | DCM | II, III | 39 | ↑ LVEF and symptoms |
| Sliwa et al. [71] | Pentoxifylline | Multiple | 6 | DCM | II, III | 28 | ↑ LVEF and symptoms |
| Sliwa et al. [72] | Pentoxifylline | Multiple | 1 | DCM | IV | 18 | ↑ LVEF and ↓ TNFα |
| Sliwa et al. [73] | Pentoxifylline | Multiple | 6 | ICM | II, III | 38 | ↑ LVEF and ↓ plasma inflammatory markers |
| Bahrmann et al. [74] | Pentoxifylline | Multiple | 6 | DCM, ICM | II, III | 47 | ↔ LVEF |
| CORONA [75] | Rosuvastatin | Multiple | 32.8 | ICM | II–IV | 5011 | ↔ Cardiovascular death, nonfatal MI, and nonfatal stroke |
| GISSI-HF [76] | Rosuvastatin | Multiple | 46.9 | DCM, ICM | II–IV | 4574 | ↔ Death and cardiovascular hospitalization |
| Krum et al. [77] | Rosuvastatin | Multiple | 6 | DCM, ICM | II–IV | 87 | ↔ LVEF |
| ACCLAIM [78] | Device-based immunomodulation | Nonspecific | 10.2 | DCM, ICM | II–IV | 2426 | ↔ Death and cardiovascular hospitalization |
| Gullestad et al. [79] | Intravenous immunoglobulin | Multiple | 6 | DCM, ICM | II, III | 40 | ↑ LVEF |
| IMAC [80] | Intravenous immunoglobulin | Multiple | 12 | DCM | I–IV | 62 | ↔ LVEF |
| METIS [82] | Methotrexate | Multiple | 3 | ICM | II–IV | 50 | ↔ 6‑Minute walk test |
ACCLAIM Advanced Chronic Heart Failure Clinical Assessment of Immunomodulation, ATTACH Anti-TNF Therapy Against Congestive Heart Failure, CORONA Controlled Rosuvastatin Multinational Trial in Heart Failure, DCM dilated cardiomyopathy, GISSI-HF Gruppo Italiano per lo Studio della Sopravvivenza nell’Insufficienza cardiaca-Heart Failure, HF heart failure, ICM ischemic cardiomyopathy, IMAC Intervention in Myocarditis and Acute Cardiomyopathy, LVEF left-ventricular ejection fraction, METIS Methotrexate Therapy on the Physical Capacity of Patients with Ischemic Heart Failure, MI myocardial infarction, RECOVER Etanercept Cytokine Antagonism in Ventricular Dysfunction, RENAISSANCE Randomized Etanercept North American Strategy to Study Antagonism of Cytokines, RENEWAL Randomized Etanercept Worldwide Evaluation