Table 2.

Potential Cardioprotective Agents That Have Been Tested in Clinical Trials to Reduce Myocardial Infarct Size or Improve Left Ventricular Function and Have Failed

Agent	Study	Outcome
Hyaluronidase	Prethrombolytic era	No effect on infarct size
Calcium channel blocker	SPRINT II; Goldbourt et al (1993)¹³	Increased mortality
Free radical scavenger, human superoxide dismutase	Flaherty et al (1994)¹⁴	No improvement in left ventricular function
Antioxidant-trimetazidine	ESPRIM; ESPRIM Group (1994)¹⁵	No effect on mortality or clinical outcomes
Fluosol	TAMI-9; Wall et al (1994)¹⁶	No decrease infarct size or increase in left ventricular function
Rheoth RX-polaxamer 188	EMIP-FR; EMIP FR Group (2000)¹⁷	No effect on death, shock, or reinfarction
White blood cell inhibitor: Anti-CD18 monoclonal antibody	FESTIVAL; Rusnak et al (2001)¹⁸	No decrease in infarct size
Na⁺/H⁺ exchange inhibitor	ESCAMI; Zeymer et al (2001)¹⁹ CASTEMI; Bar et al (2006)²⁰	No effect on infarct size, clinical outcomes, left ventricular ejection fraction
Complement inhibitors	COMPLY Trial; Mahaffey et al (2003)²¹ APEX Trial; Armstrong and Granger (2007)²²	No decrease in infarct size or decrease in mortality
Magnesium	Magnesium in Coronaries Trial Investigators (2002)²³	No effect on mortality, heart failure, or ventricular tachycardia
Nicorandil	Kitakaze et al (2007)²⁴	No effect on mortality or infarct size
Cold perfusion	CHILL-MI; Erlinge et al (2014)²⁵	No effect on infarct size or left ventricular ejection fraction
Sodium nitrite	NIAMI; Siddiqi et al (2014)²⁶	No decrease in infarct size, no effect on left ventricular ejection fraction
MPTP inhibitor	MITOCARE; Atar et al (2014)²⁷	No effect on infarct size or left ventricular ejection fraction
Cyclosporine	CIRCUS; Cung et al (2015)²⁸	No effect on deaths or heart failure

Adapted and extended from Robert Kloner, MD, National Institutes of Health Workshop on New Horizons in Cardioprotection, 2011. APEX indicates Pexelizumab in Conjunction With Angioplasty in Acute Myocardial Infarction; CASTEMI, Caldaret in ST Elevation MI; CHILL-MI, Rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction; CIRCUS, Cyclosporine and Prognosis in Acute Myocardial Infarction Patients; COMPLY, Complement inhibition in myocardial infarction treated with thrombolytics; EMIP-FR, European Myocardial Infarction Project - Free Radicals; ESCAMI, Evaluation of the safety and cardioprotective effects of eniporide in acute myocardial infarction; FESTIVAL, An anti-CD11/CD18 monoclonal antibody in patients with acute myocardial infarction having percutaneous transluminal coronary angioplasty; MITOCARE, Effect of intravenous TRO40303 as an adjunct to primary percutaneous coronary intervention for acute ST-elevation myocardial infarction; MPTP, mitochondrial permeability transition pore; NIAMI, intravenous sodium nitrite in acute ST-elevation myocardial infarction; SPRINT II, Systolic Blood Pressure Intervention Trial II; and TAMI-9, Thrombolysis and Angioplasty in Myocardial Infarction-9.