Table 3.
Clinical trials of NLRP3 inflammasome and IL-1 or IL-6 blockers in CVDs.
| Clinical drugs | Indication (n) | Study design | Outcomes | Refs |
|---|---|---|---|---|
| Canakinumab (2017) | Patients with previous AMI at least 30 days and undergoing revascularization, whose high-sensitivity CRP > 2 mg/L (10061) | Randomized, canakinumab 50, 150, or 300 mg, or placebo subcutaneously given every 3 months for a median follow-up of 3.7 years | Reduced high-sensitivity CRP levels without reducing the LDL level; Reduced the incidence of primary endpoint of cardiac death, non-fatal AMI at dose of 150 mg | (144) |
| Canakinumab (2019) | Patients with prior myocardial infarction and high CRP > 2 mg/L (10061) | Randomized, canakinumab 50,150,300 mg, or placebo subcutaneously given every 3 months for a median follow-up of 3.7 years | A dose-dependent reduction in the composite of hospitalization for heart failure and heart failure-related mortality | (145) |
| Anakinra (2013) | Patient with stable STEMI (30) | Randomized, anakinra or placebo subcutaneously given 100 mg/day for 14 days for a follow-up of 10-14 weeks | Blunted the acute inflammatory response; led to a lower incidence of heart failure | (147) |
| Anakinra (2015) | Patient with stable STEMI (40) | Randomized, anakinra or placebo subcutaneously given 100 mg/day for 14 days for a follow-up of 28 months | A neutral effect on recurrent ischemic events; may prevent new-onset heart failure | (148) |
| Anakinra (2015) | Patient with non-ST elevation ACS presenting <48 h from onset of chest pain (182) | Randomized, IL-1Ra (anakinra) or placebo subcutaneously given 100 mg/day for 14 days for a follow-up of 12 months | Reduced high-sensitive CRP but rose again at 30 days; major adverse cardiovascular events had no difference at 30 days or 3 months but increased at 1 year | (149) |
| Anakinra (2008) | Patients with rheumatoid arthritis (23:19) | Non-randomized anakinra 150 mg/day or prednisolone subcutaneously given for 30 days | Improved biomarkers and vascular and LV function after 30 days of treatment | (150) |
| Anakinra (2017) | Patients with reduced LV ejection fraction (<50%) and elevated CRP levels (>2 mg/L), within 14 days of hospital discharge (60) | Randomized, anakinra or placebo subcutaneously given 100 mg/day for 2 and 12 weeks with a follow-up of 24 weeks | Improved peak oxygen consumption and reduced the incidence of death or rehospitalization | (151) |
| Anakinra (2016) | Patients with acute decompensated heart failure, reduced LV ejection fraction (<40%), and elevated CRP levels (>5 mg/L) (30) | Randomized, anakinra or placebo 100 mg subcutaneously given twice daily for 3 days followed by once daily for 11 days | Reduced levels of CRP, IL-6, and systemic inflammatory response | (152) |
| Tocilizumab (2021) | Patients with STEMI within 6 h of symptom (199) | Randomized, a single intravenous infusion of 280 mg of tocilizumab or placebo with a follow-up of 6 months | Reduced microvascular obstruction, although no effect on the final infarct size | (154) |
| Colchicine (2011) | Patients with clinically stable coronary disease for at least 6 months (532) | Randomized, colchicine 0.5 mg or placebo given daily for a median follow-up of 3 years | Colchicine 0.5 mg/day in addition to statins and other secondary prevention therapies reduced the risk of cardiovascular events | (158) |
| Colchicine (2015) | Patients with STEMI ≤12 h from pain onset (151) | Randomized, colchicine given a loading dose of 2 mg, and continued with 0.5 mg twice daily, or placebo, for 5 days | Reduced the relative infarct size and the incidence of acute coronary syndrome | (159) |
| Colchicine (2021) | Patients with STEMI referred for primary percutaneous coronary intervention (192) | Randomized, colchicine or placebo given a 2-mg loading dose followed by 0.5 mg twice daily, for 5 days with a follow-up of 3 months | No significant difference in infarct size and LV remodeling between the colchicine and placebo groups | (160) |
| OLT1177 (2021) | Patients with heart failure and reduced ejection fraction (30) | Randomized, OLT1177 at dose of 500, 1,000, and 2,000 mg for up to 14 days, each including 10 patients | OLT1177 was safe and well tolerated, and LV ejection fraction improved significantly in the 2,000-mg group | (161) |
CVDs, cardiovascular diseases; AMI, acute myocardial infarctions; CRP, C-reactive proteins; LDL, low-density lipoproteins; STEMI, ST-segment elevation myocardial infarction.