Table 2.

Trials studying the effects of anti-inflammatory therapy for myocardial infarction

Trial	IMP	Study population	Phase of MI	Study design	N	IMP delivery protocol	Duration of IMP delivery	Effect on clinical outcome	Effects on structural parameters	Effects on functional parameters	Effects on biomarkers
CANTOS	Canakinumab (anti-IL-1β−AB)	H/o MI ≥ 30 days prior to randomization, presence of RIR as defined by hsCRP ≥ 2 mg/L	Late	Phase 3 RCT	10 061	First dose > 30 days after MI, then every 3 months	Median f/u = 3.7 years	Lower rate of recurrent cardiovascular events			Reduction in CRP and IL-6 levels
VCU-ART	Anakinra (IL-1RA)	STEMI with <24 h since onset of chest pain with successful PCI	Acute (<24 h)	RCT, pilot	10	First dose within 24 h since onset of chest pain, after successful PCI, then every 24h	14 days		No difference in infarct size measured by CMR	Reduction in LVESVi
VCU-ART2	Anakinra	STEMI with <24 h since onset of chest pain with successful PCI	Acute (<24 h)	RCT, pilot	30	First dose within 24 h since onset of chest pain, after successful PCI, then every 24 h	14 days			No significant difference in LVESVi, LVEDVi, and LVEF	Blunted interval change in CRP between admission and 72 h
VCU-ART3	Anakinra	STEMI with PCI within 12 h after onset of symptoms	Acute (<12 h)	Phase 2 RCT	99	First dose within 12 h of PCI, then every 24 h	14 days	Lower incidence of HF-related clinical events		No difference in LVESV or LVEF	Decrease in AUC of hsCRP during the first 14 days post-STEMI
MRC-ILA	Anakinra	NSTEMI presenting within 48 h of symptom onset, no intention of urgent revascularization within 3 months	Subacute (<48 h)	Phase 2 RCT	182	First dose within 24 h of positive Trop, then every 24 h	14 days	Significant increase in MACE at 1-year f/u	No difference in CMR sub-study		Decrease in AUC of hsCRP during the first 7 days of treatment, increase in absolute hsCRP from Day 14 to Day 30, decrease in white cell count over treatment period, no difference in AUC of Trop during the first 7 days
COLCOT	Colchicine	MI within 30 days prior to enrolment that have undergone PCI and were on OMT	Late	Phase 3 RCT	4745	First dose within 30 days after MI, after completion of PCI, then daily doses	Ca. 23 months	Lower incidence of ischaemic cardiovascular events			Trend towards lower CRP
CLEVER-ACS	Everolimus	STEMI within 5 days of PCI	Subacute	Phase 2 RCT	150	Daily oral dose for 5 days	5 days		No difference in infarct size or microvascular obstruction (CMR)
CIRT	Methotrexate	H/o MI and/or multivessel CAD with completion of planned revascularization plus either T2-DM or metabolic syndrome, medically stable for ≥60 days from index MI	Late	Phase 3 RCT	4786	Weekly dose of MTX plus folate daily	Median f/u = 2.3 years	No difference in cardiovascular events and all-cause mortality			No reduction in CRP levels, IL-1β, or IL-6
Trial	IMP	Study population	Phase of MI	Study design	N	IMP delivery protocol	Duration of IMP delivery	Effect on clinical outcome	Effects on structural parameters	Effects on functional parameters	aEffects on biomarkers
Piot et al.	Cyclosporine	STEMI presenting within 12 h after onset of symptoms	Acute (<12 h)	RCT, pilot	58	Single bolus dose immediately before PCI			Reduction of infarct size in CMR 5 days post-PCI	No difference in LVEF after 3 months	Reduction in AUC for CK within first 72 h, non-significant reduction in AUC for Trop-I
CIRCUS	Cyclosporine	STEMI presenting within 12 h after onset of symptoms with culprit lesion in LAD	Acute (< 12 h)	Phase 3 RCT	970	Single bolus dose immediately before PCI		No reduction in death from any cause, worsening of HF during the initial hospitalization, rehospitalization for heart failure		No difference in LVEF, LVEDV, or LVESV	No difference in total CK at any timepoint
CYCLE	Cyclosporine	STEMI presenting within 6 h after onset of symptoms	Acute (<6 h)	Open-label, Phase 2 RCT	410	Single bolus dose immediately before PCI		No difference in combined endpoint of all-cause mortality, cardiogenic shock and HF		No difference in LVEF	No difference in Trop-T or CK
Kleveland et al.	Tocilizumab (anti-IL-6-AB)	NSTEMI scheduled for coronary angiography, median of 2 days after onset of symptoms	Subacute (mean of 2 days)	Phase 2 RCT	117	Single bolus dose immediately before coronary angiography				No difference in LVEF	Reduction in AUC for hsCRP and Trop-T within 3 days
ASSAIL-MI	Tocilizumab	STEMI presenting within 6 h after onset of symptoms	Acute (<6 h)	Phase 2 RCT	299	Single bolus dose during PCI			Increased myocardial salvage and lower microvascular obstruction at 3–7d		Reduction in AUC for hsCRP during hospitalization
APEX-AMI	Pexelizumab (anti-C5-AB)	STEMI presenting within 6 h after onset of symptoms scheduled for PCI	Acute (<6 h)	Phase 3 RCT	5745	Single bolus dose prior to PCI		No difference in 30-day-mortality, HF, shock, or recurrent MI
Sub-study of APEX-AMI	Pexelizumab	Idem	Idem	Sub-study	99	Idem			Reduced infarct size at baseline (Day 5) and f/u (Day 90) in CMR	Improved LVEF by CMR
COMMA	Pexelizumab	STEMI presenting within 6 h after onset of symptoms scheduled for PCI	Acute (<6 h)	Phase 3 RCT	960	Bolus dose prior to PCI followed by infusion with start 4 h after first dose	20 h	Reduction in mortality at 90 days			No difference in AUC for CK

AB, antibody; AUC, area under the curve; C5, complement component 5; CAD, coronary artery disease; CK, creatinine kinase; CMR, cardiac magnetic resonance; CRP, C-reactive protein; f/u, follow-up; hs, high-sensitivity; H/o, history of; IL-1RA; interleukin-1 receptor antagonist; MI, myocardial infarction; LAD, left anterior descending coronary artery; LVESVI, left ventricular end-systolic volume index; LVEDVI, left ventricular end-diastolic volume index; LVESV, left ventricular end-systolic volume; MTX, methotrexate; NSTEMI, non-ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention; RCT, randomized controlled trial; STEMI, ST-segment elevation myocardial infarction; Trop, troponin; for abbreviations of trials, please refer to the text.