Custodiol versus Plegisol: A phase 3 multicentre myocardial protection study

Area of Science:

• Cardiovascular Surgery
• Cardioplegia Solutions
• Cardiac Protection

Background:

• Crystalloid antegrade cardioplegia solutions are widely used but lack extensive prospective multicenter comparison trials.
• Evaluating novel cardioplegia solutions is crucial for improving patient outcomes in cardiac surgery.

Purpose of the Study:

• To compare the efficacy and safety of a single-administration histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution against a standard multidose extracellular product (Plegisol [PL]).
• To assess myocardial protection and adverse event rates in isolated coronary bypass patients receiving different cardioplegia strategies.

Main Methods:

• An open-label, randomized, prospective trial involving 136 isolated coronary bypass patients across seven institutions.
• Patients were assigned to receive either Custodiol HTK or Plegisol (PL) and stratified by ejection fraction.
• Key outcome measures included defibrillation frequency, hospital/ICU stay, cardiac enzyme levels, and adverse events.

Main Results:

• Fewer defibrillations were required with HTK (64%) compared to PL (91%).
• The primary endpoint, cardiac troponin I (cTn-I) levels at 6 hours post-ischemia, favored PL (16.7±13.2 μg/L vs. 20.3±13.5 μg/L, P=0.01).
• HTK treatment was associated with higher cTn-I levels (OR 3.5, P=0.01), particularly in patients undergoing circumflex grafting, and 48% required reinfusions.

Conclusions:

• Histidine-tryptophan-ketoglutarate (HTK) cardioplegia resulted in greater structural protein release and more adverse events than Plegisol (PL), even with reinfusion.
• The findings suggest potential limitations of HTK in providing myocardial protection compared to standard multidose solutions in this patient cohort.