Potential pharmacological strategies for reducing MI size and improving clinical outcomes in patients presenting with reperfused STEMI
| Clinical study | Therapeutic intervention (patient population) | N | Main outcomes | Mechanism of cardioprotection and other comments |
|---|---|---|---|---|
| Atrial natriuretic peptide | ||||
| Kitakaze et al18 | IV Carperitide (atrial natriuretic peptide analogue) 72 h infusion started prior to PPCI (All-comer STEMI) | 569 | 15% reduction in MI size (72 h AUC total CK) 2.0% absolute increase in LVEF | Atrial natriuretic peptide targets prosurvival kinase pathways such as the cGMP and RISK pathways |
| Ciclosporin A | ||||
| Piot et al19 20 | IV Ciclosporin A (2.5 mg/kg Sandimmune) bolus 10 min prior to PPCI (LAD/RCA STEMI, TIMI 0) | 58 | 44% reduction in MI size (72 h AUC total CK) 20% reduction in MI size (CMR subset) 28% reduction in MI size and smaller LVESV on CMR at 6 months | Ciclosporin A inhibits the opening of the mitochondrial permeability transition pore, a critical determinant of lethal myocardial reperfusion injury |
| Cung et al21 CIRCUS | IV Ciclosporin A (2.5 mg/kg Ciclomulsion) bolus 10 min prior to PPCI (LAD STEMI, TIMI 0) | 791 | No effect on the primary end point at 1 year of all-cause mortality, rehospitalisation for heart failure and adverse LV remodelling by echocardiography (59.0% Ciclosporin A vs 58.1% Control) | The reason for the neutral study is unclear but may relate to the Ciclomulsion preparation or failure of the drug to reach its molecular target. . |
| CYCLE NCT01650662 | IV Ciclosporin-A (2.5 mg/kg Sandimmune) bolus 5 min prior to PPCI (LAD STEMI, TIMI 0/1) | 410 | Ongoing study Primary end point of ST-segment resolution ≥70% 1 h after PPCI | Recruitment complete October 2014—results awaited |
| CAPRI NCT02390674 | IV Ciclosporin-A (2.5 mg/kg Sandimmune) bolus prior to PPCI (All-comer STEMI) | 68 | Ongoing study Primary end point MI size (3 month CMR) | |
| Exenatide | ||||
| Lonborg et al22 23 | IV infusion of Exenatide started 15 min prior to PPCI and continued for 6 h (All-comer STEMI, TIMI 0/1) | 105 | 23% reduction in MI size (3 month CMR) Increase in myocardial salvage index (0.62–0.71) Short ischaemic times (≤132 minutes) associated with greater myocardial salvage | Exenatide, a GLP-1 analogue, targets prosurvival kinase pathways such as the RISK pathway |
| Woo et al24 | S/C injection of Exenatide prior to PPCI (All-comer STEMI, TIMI 0) | 58 | 52% reduction in MI size (1 month CMR) 27% reduction in MI size (72 h AUC CK-MB) 54% reduction in MI size (72 h AUC Trop-I) | |
| EMPRES NCT01938235 | IV infusion of Exenatide for 24 h (All-comer STEMI, TIMI 0/1) | 198 | Ongoing study Primary end point of MI size at 3 months over area-at-risk at 72 h post randomisation (using CMR) | |
| Metoprolol | ||||
| Ibanez et al25 26 | IV Metoprolol (3×5 mg) in ambulance prior to PPCI (LAD STEMI) | 270 | 20% reduction in MI size (7 day CMR) 3.7% absolute increase in LVEF (6 months CMR) 59% reduction in the incidence of poor LVEF (<35%) (6 months CMR) 65% reduction in need for ICD by 65% at 6 months 68% reduction in HHF at 2 years | The mechanism of cardioprotection is not clear. |
| Roovlink et al EARLY BAMI | IV Metoprolol (3×5 mg) in ambulance prior to PPCI (LAD STEMI) | 408 | Ongoing study Primary end point of MI size at 30 days on CMR | Ongoing study selecting patients with STEMI presenting within 12 h of onset of symptoms |
AUC, area under curve; cGMP, cyclic guanosine monophosphate; CK, creatine kinase; CK-MB, creatine kinase myocardial band; CMR, cardiovascular magnetic resonance; GLP-1, glucagon-like peptide-1; HHF, hospitalisation for heart failure; ICD, implantable cardiac defibrillator; ICD, implantable cardiac defibrillator; IV, intravenous; LAD, left anterior descending artery; LVEF, left ventricular ejection fraction; LVESV, left ventricular end systolic volume; LVESV, left ventricular end-systolic volume; MI, myocardial infarct; PPCI, primary percutaneous coronary intervention; RCA, right coronary artery; RISK, reperfusion injury salvage kinase; STEMI, ST-segment elevation myocardial infarction; S/C, subcutaneous; TIA, transient ischaemic attack; TIMI, Thrombolysis in Myocardial infarction; Trop, troponin.