Table 1.
Major completed clinical trials involving anti-inflammatory agents in atherosclerotic heart disease.
| Trial name | Study design | Study population | Patient number | Follow-up (years) | Intervention | Target | Primary outcomes | Result |
|---|---|---|---|---|---|---|---|---|
| Therapy with a clear target | ||||||||
| Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-ST-elevation myocardial infarction (23) | Phase II, two-center, double-blind, placebo-controlled trial | Patients with NSTEMI | 117 | 0.5 | Tocilizumab 280 mg prior to coronary angiography vs. Placebo | Il-6ra | Auc for hscrp during hospitalization | 4.2 mg/L/h (placebo) vs. 2.0 mg/L/h (tocilizumab); p < 0.001 |
| ASSAIL-MI (24) | Phase II randomized, double blind, placebo-controlled trial | Patients with first-time STEMI presenting within 6 h of the onset of chest pain | 199 | 0.5 | Tocilizumab 20 mg/ml once vs. Placebo | Il-6ra | Myocardial salvage index | Completed, results not published |
| MRC-ILA Heart (25) | Phase II, double-blinded, randomized, placebo-controlled | Patients with NSTE-ACS, presenting <48 h from onset of chest pain | 182 | 1.0 | 100 mg of anakinra once daily vs. Placebo | Il-1ra | Auc for c-reactive protein over the first 7 days | IL-1Ra group, 21.98 mg day/L (95%CI 16.31–29.64) vs. placebo group, 43.5 mg day/L (31.15–60.75); p = 0.0028 |
| CANTOS (19) | Phase III multicenter, randomized, double-blind, placebo-controlled | Patients with MI and elevated hsCRP | 10,061 | 2.1 | Canakinumab (50, 150, or 300 mg) every 3 months vs. Placebo | Il-1β | Non-fatal mi, non-fatal stroke and cardiovascular death | HR 0.85;95% CI 0.75–0.98; p = 0.021 in 150 mg- treated group |
| LATITUDE-TIMI 60 (26) | Phase III multicenter, randomized, double-blind, placebo-controlled | Patients had been hospitalized with a presumed spontaneous (type 1) MI | 3,503 | 0.4 | Twice-daily losmapimod 7.5 mg vs. Placebo | Mapk | Composite of cardiovascular death, mi, or severe recurrent ischemia requiring urgent coronary revascularization | HR 1.16; 95% CI, 0.91–1.47; p = 0.24 |
| SOLID-TIMI 52 (27) | Phase III multicenter, randomized, double-blind, placebo-controlled | Patients within 30 days of hospitalization with an ACS | 13,026 | 2.5 | Once-daily darapladib 160 mg vs. Placebo | Lp-pla2 | Composite of coronary heart disease (chd) death, mi, or urgent coronary revascularization for myocardial ischemia | HR 1.00;95% CI, 0.91–1.09; p = 0.93 |
| Broad-spectrum anti-inflammatory approach | ||||||||
| CIRT (20) | Phase III multicenter, randomized, double-blind, placebo- controlled trial | Patients with previous myocardial infarction or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome | 4,786 | 2.3 | Methotrexate (target dose of 15–20 mg weekly) vs. Placebo | Multiple | Non-fatal mi, non-fatal stroke and cardiovascular death | HR 1.01; 95% CI 0.82–1.25; p = 0.91 |
| LoDoCo (21) | Prospective, randomized, observer-blinded | Patients with stable coronary disease | 532 | 3.0 | Colchicine 0.5 mg/day vs. Placebo | Multiple | Composite incidence of acute coronary syndrome, out-of-hospital cardiac arrest, or non-cardioembolic ischemic stroke | HR 0.29; 95% CI: 0.15 to 0.56; p < 0.001 |
| COLCOT (28) | Phase III multicenter, randomized, double-blind, placebo- controlled trial | Patients recruited within 30 days after a myocardial infarction | 4,745 | 1.8 | Colchicine 0.5 mg/day vs. Placebo | Multiple | Composite of death from cardiovascular causes, resuscitated cardiac arrest, myocardial infarction, stroke, or urgent hospitalization for angina leading to coronary revascularization | HR 0.77; 95% CI, 0.61 to 0.96; p = 0.02 |
| LoDoCo 2 (22) | Phase III multicenter, randomized, double-blind, placebo- controlled trial | Patients with chronic coronary disease | 5,522 | 2.3 | Colchicine 0.5 mg/day vs. Placebo | Multiple | Composite of cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization | HR 0.69; 95% CI, 0.57 to 0.83; p < 0.001 |
| COPS (29) | Multicenter, randomized, double-blind, placebo-controlled trial | Patients with acs and had evidence of coronary artery disease on coronary angiography | 795 | 1.0 | Colchicine 0.5 mg twice daily for first month, then 0.5 mg daily for 11 months | Multiple | Composite of all-cause mortality, acs, ischemia-driven (unplanned) urgent revascularization and non-cardioembolic ischemic stroke | HR 0.65; 95% CI, 0.38 to 1.09; p = 0.10 |
CI, confidence interval; HR, hazard ratio; IL, interleukin; MI, myocardial infarction; Ra, receptor antagonist; AUC, area under the curve; NSTEMI, non-ST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; ACS, acute coronary syndrome; MAPK, p38 mitogen-activated protein kinase; Lp-PLA2, lipoprotein-associated phospholipase A2.