Table 1.
Main trials of anti-inflammatory strategies to avert cardiovascular events
| First author and reference | Study name | Year of start and follow-up duration | Study population | Intervention | End points | Results |
|---|---|---|---|---|---|---|
| Ridker et al.,68 USA | JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosurvastatin) | 2003, median follow-up of 1.9 years (maximum, 5.0) | Healthy people with high levels of hsCRP (≥2 mg/L), but LDL-C 130 mg/dL (3.4 mmol/L) | Rosuvastatin 20 mg daily | MI, stroke, arterial revascularization, hospitalization for unstable angina, or death from CV causes | Rosuvastatin reduced LDL-C levels, hsCRP levels, and the main CV outcome |
| Ridker et al.,69 USA | CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) | 2011, median follow-up of 3.7 years | Patients with previous MI and hsCRP ≥2 mg/L | Canakinumab 50 or 150 or 300 mg every 3 months | Nonfatal MI, nonfatal stroke, or CV death | The 150 mg dose of canakinumab every 3 months led to a rate of recurrent CV events significantly lower than placebo |
| Kleveland et al.,70 Norway | Effect of a single dose of the IL-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with NSTEMI | 2011, follow-up of 6 months | Patients with NSTEMI | Single dose of 280 mg of tocilizumab | hsCRP and hsTnT | Tocilizumab attenuated the inflammatory response and TnT release |
| Ridker et al.,71 USA | CIRT (CV Inflammation Reduction Trial) | 2013, median follow-up of 2.3 years | Patients with previous MI or multivessel coronary disease who additionally had either type 2 diabetes or the metabolic syndrome | Methotrexate 15–20 mg weekly | Composite of MI, stroke, CV death or hospitalization for unstable angina that led to urgent revascularization | Methotrexate did not reduce levels of IL-1β, IL-6, or hsCRP and did not result in fewer CV events than placebo |
| Nidorf et al.,6 USA | LoDoCo (Low-Dose Colchicine) | 2013, median follow-up of 3 years | Patients with stable coronary disease receiving aspirin and/or clopidogrel and statins | Colchicine 0.5 mg daily | A composite of acute coronary syndrome, cardiac arrest or ischaemic stroke | Colchicine 0.5 mg daily was safe and effective in reducing the risk of CV events |
| Nidorf et al.,9 USA | LoDoCo2 | 2014, 30-Day run-in phase | Patients with stable coronary disease receiving aspirin and/or clopidogrel and statins | Colchicine 0.5 mg daily | Reduce the incidence of composite acute coronary syndrome, cardiac arrest or ischaemic stroke | Confirmation of the safety and benefit of colchicine 0.5 mg daily for secondary prevention of CV events |
| Hennessy et al.,72 Australia | LoDoCo-MI (Low-Dose Colchicine after Myocardial Infarction) | 2015, follow-up of 30 days | Patients with acute MI | Colchicine 0.5 mg daily | Proportion of patients with residual hsCRP level ≥2 mg/L after 30 days of treatment | The treatment was safe and well tolerated, but it was not associated with a significant reduction of hsCRP level |
| Tardif et al.,8 Canada | COLCOT (Colchicine CV Outcomes Trial) | 2015, median follow-up of 22.6 months | Patients within 30 days after an MI | Colchicine 0.5 mg daily | A composite of death from CV causes, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina leading to coronary revascularization | Colchicine produced a 23% lower composite efficacy endpoint but did not lower hsCRP level compared to placebo |
| Giles et al.,73 USA | ENTRACTE (A Clinical Outcomes Study to Evaluate the Effects of IL-6 Receptor Blockade With Tocilizumab in Comparison With Etanercept on the Rate of CV Events in Patients With Moderate to Severe Rheumatoid Arthritis) | 2016, follow-up of 4.9 years | Patients with active RA who had inadequate response to conventional synthetic disease-modifying antirheumatic drugs and who had at least 1 CV risk factor | Tocilizumab 8 mg/kg/month or Etanercept 50 mg/week | Comparison of time to first occurrence of a major adverse CV event | Tocilizumab was associated with a relative risk of 1.43 for the occurrence of major CV events compared to etanercept |
CV, cardiovascular; hsCRP, high-sensitivity C-reactive protein; IL, interleukin; LDL-C, low-density lipoprotein cholesterol; MI, myocardial infarction; NSTEMI, non-ST elevation MI; RA, rheumatoid arthritis.