Table 1.

Therapeutic strategies to prevent periprocedural myocardial injury and type 4a myocardial infarction in chronic coronary syndrome patients.

Agent	Timing of administration	Potential mechanism of action	Findings
High-dose Statins	Pre-PCI	Pleiotropic effect on inflammation [161,162] Production of endothelial progenitor cells [162]	Several RCTs have reported ↓ incidence of periprocedural myocardial injury and type 4a MI [[154], [155], [156], [157]]. A meta-analysis of 14 trials reported ↓ incidence of periprocedural myocardial injury, type 4a MI and MACE (death, re-infarction and revascularization [158]). However, neutral effects in some studies [159,160].
Cangrelor	At the time of PCI (intravenous)	Intravenous P2Y12 platelet inhibitor	Large multicentre RCT (CHAMPION PHOENIX) of 11,145 CCS patients reported ↓ incidence of periprocedural myocardial injury and type 4a MI when compared to clopidogrel [150]
Remote ischemic conditioning	Pre-PCI (3–4 5-min cycles of limb ischemia/reperfusion)	Reduces acute myocardial ischemia-reperfusion injury	Mixed results with some positive studies reporting ↓ incidence of periprocedural myocardial injury and type 4a MI [[163], [164], [165]], with other studies showing no reduction in PMI [166] One follow-up RCT of 225 CCS patients showing ↓ incidence of MACE (not powered for clinical outcomes) [167] Meta-analysis of 11 studies showed no overall benefit with RIC [168]
Vitamin C	Pre-PCI (IV infusion)	Anti-oxidant effects	RCT of 532 CCS patients showing ↓incidence of periprocedural myocardial injury [151] RCT of 56 CCS patients showed ↑microcirculatory reperfusion [152].
Enalaprilat	At the time of PCI (intracoronary)	Endothelium-dependent epicardial coronary vasodilation mediated by endogenous bradykinin activity	RCT of 40 CCS patients showing ↓ incidence of periprocedural myocardial injury [153]
Colchicine	At the time of PCI	Anti-inflammatory effects	RCT [172] of 400 CCS did not show any impact on PCI-related myocardial injury. RCT of 5545 CCS patients showed 31% reduction in cardiovascular death, spontaneous (nonprocedural) myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. However, the incidence of death from noncardiovascular causes was higher in the colchicine group than in the placebo group (HR 1.51) [171].