Table 1.
Clinical study | Therapeutic intervention (patient population) |
N | Main outcomes | Mechanism of cardioprotection potential reasons for neutral results |
---|---|---|---|---|
Therapeutic hypothermia | ||||
Erlinge et al10 CHILL-MI | IV 600 to 2000 mL cold saline and endovascular cooling prior to PPCI for 1h to cool to 34.7°C | 120 | No effect on primary end point of MI size (CMR at 4 days) Delays reperfusion by 9 min |
Experimental studies show that mild hypothermia, induced before reperfusion reduced MI size. The reasons for the neutral study are unclear but may relate to: 20%–27% of patients had TIMI flow of > 0 before PPCI Only 76% of patients had a temperature of <35°C at reperfusion Interestingly, post-hoc sub-group analysis revealed that patients presenting early (<4 h) with anterior STEMI had a smaller MI/AAR |
Nichol et al11 VELOCITY | Peritoneal hypothermia to cool to 34.7°C | 57 | No effect on primary end point of MI size (CMR at 3–5 days) Delays reperfusion by 15 min Increase in stent thrombosis |
The reasons for the neutral study may relate to:
|
Targeting mitochondrial function | ||||
Lincoff et al12 PROTECTION-AMI | IV delcasertib infusion for 2.5 h (LAD/RCA STEMI) |
1010 | No effect on primary end point of AUC CK-MB | Peptide inhibitor of delta-protein kinase C a major mediator of the mitochondrial apoptotic pathway which has been reported in animal studies to reduce MI size when administered prior to reperfusion.The reasons for the neutral study is unclear but may relate to:
|
Atar et al13 MITOCARE | IV bolus of TRO40303 prior to angioplasty (All-comer STEMI, TIMI <1) |
163 | No effect on primary end point of 72 h AUC CK-MB/Troponin-T | This drug is an indirect inhibitor of the mitochondrial permeability transition pore which has been reported in animal studies to reduce MI size when administered prior to reperfusion.The reason for the neutral study is unclear but may relate to:
|
Chakrabarti et al14 EMBRACE-STEMI | IV infusion (75 min) of Bendavia started 15 min before reperfusion (LAD STEMI, TIMI 0) |
118 | No effect on the primary end point of 72 h AUC CK-MB | A mitochondria-targeting peptide which has been reported in animal studies to reduce MI size when administered prior to reperfusion. The reason for the neutral study is unclear but may be because the study was underpowered. Full study results are awaited. |
Nitric oxide signalling | ||||
Siddiqi et al15 (NIAMI) |
IV sodium nitrite (70 µmol) over 5 min prior to PPCI (All-comer STEMI, TIMI<1) |
229 | No effect on the primary end point of 72 h AUC CK-MB | The reason for the neutral study is unclear but may relate to the route of drug administration and the fact that >90% of patient had received GTN prior to reperfusion |
Jones et al16 NITRITE | IC sodium nitrite (1.8 μmol) bolus prior to angioplasty (All-comer STEMI) |
80 | No effect on the primary end point of MI size (as % LV mass) (on 6–8 days CMR) | The reason for the neutral study is unclear but may relate to patient selection as post-hoc subgroup analysis revealed reduced MI size in patients with LAD STEMI |
NOMI NCT01398384 |
Inhaled nitric oxide at 80 ppm for 4 h initiated prior to PPCI | 248 | No effect on the primary end point of MI size (as % of LV mass) on CMR (48–72 h) | The reason for the neutral study is unclear but may relate to patient selection (post-hoc subgroup analysis revealed reduced MI size in patients with LAD STEMI) and prior dosing with IC/IV GTN as patients who were GTN-naïve, there was a reduction in MI size |
AUC, area under curve; CK-MB, creatine kinase myocardial band; CMR, cardiovascular MRI; GTN, glyceryl trinitrate; IC, intracoronary; IV, intravenous; LAD, left anterior descending artery; MI, myocardial infract; PPCI, primary percutaneous coronary intervention; RCA, right coronary artery; STEMI, ST-segment elevation myocardial infarction; TIMI, Thrombolysis in MI.