Cardiac protection with phosphocreatine: a meta-analysis
Giovanni Landonia, Alberto Zangrilloa, Vladimir V. Lomivorotovc
, Valery Likhvantsevd
, Jun Mae
,
Francesco De Simonea and Evgeny Fominskiya
Phosphocreatine (PCr) plays an important role in the energy metabolism of the heart and a decrease in its intracellular concentration
results in alteration of myocardium energetics and work. We conducted a meta-analysis of all randomized and matched trials that compared
PCr with placebo or standard treatment in patients with coronary artery disease or chronic heart failure or in those undergoing
cardiac surgery. We systematically searched PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials and Google Scholar
up to 1 November 2015, for pertinent trials. The primary outcome was all-cause mortality. Secondary outcomes included inotrope use,
ejection fraction (EF), peak creatinine kinase-myocardial band (CK-MB) release and the incidence of major arrhythmias, as well as spontaneous
recovery of the heart performance in the subgroup of patients undergoing cardiac surgery with cardiopulmonary bypass. We pooled
odds ratio (OR) and mean difference (MD) using fixed- and random effects models. We identified 41 controlled trials, of them 32 were
randomized. Patients receiving PCr had lower all-cause mortality when compared with the control group [61/1731 (3.5%) vs 177/1667
(10.6%); OR: 0.71, 95% CI: 0.51–0.99; P = 0.04; I
2 = 0%; with 3400 patients and 22 trials included].
Phosphocreatine administration was
associated with higher LVEF (MD: 3.82, 95% CI: 1.18–6.46; P = 0.005; I
2 = 98%), lower peak CK-MB release (MD: −6.08, 95% CI: −8.01,
−4.15; P < 0.001; I
2 = 97%), lower rate of major arrhythmias (OR: 0.42; 95% CI: 0.27–0.66; P < 0.001; I
2 = 0%), lower incidence of inotropic
support (OR: 0.39, 95% CI: 0.25–0.61; P < 0.001; I
2 = 56%) and a higher level of spontaneous recovery of the heart performance after cardiopulmonary
bypass (OR: 3.49, 95% CI: 2.28–5.35; P < 0.001; I
2 = 49%) when compared with the control group. In a mixed population of
patients with coronary artery disease, chronic heart failure or in those undergoing cardiac surgery, PCr may reduce all-cause short-term
mortality. In addition, PCr administration was associated with improved cardiac outcomes. Owing to the pharmacological plausibility of
this effect and to the concordance of the beneficial effects of PCr on several secondary but important outcomes and survival, there is
urgent need for a large multicentre randomized trial to confirm these findings.
FULL ARTICLE:
http://icvts.oxfordjournals.org/content/early/2016/06/17/icvts.ivw171.full.pdf+html
Keywords: Phosphocreatine • Cardiac surgery • Myocardial infarction • Heart failure • Mortality
