Effect of dipyridamole on myocardial reperfusion injury: A double‐blind randomized controlled trial in patients undergoing elective coronary artery bypass surgery

Abstract

Dipyridamole reduces reperfusion-injury in preclinical trials and may be beneficial in patients undergoing coronary angioplasty, but its effect on patients undergoing coronary artery bypass grafting (CABG) is unknown. We hypothesized that dipyridamole limits myocardial reperfusion-injury in patients undergoing CABG. The trial design was a double-blind trial randomizing between pretreatment with dipyridamole or placebo. In all, 94 patients undergoing elective on-pump CABG were recruited between February 2010 and June 2012. The primary endpoint was plasma high-sensitive (hs-) troponin-I at 6, 12, and 24 hours after reperfusion. Secondary endpoints were the occurrence of bleeding, arrhythmias, need for inotropic support, and intensive care unit length of stay. Finally, 79 patients (33 dipyridamole) were included in the per-protocol analysis. Dipyridamole did not significantly affect postoperative hs-troponin-I (change in plasma hs-troponin I 23% [95% confidence interval 223% to 36%]; P > 0.1). Secondary endpoints did not differ between groups. Dipyridamole prior to CABG does not significantly reduce postoperative hs-troponin release. Study Highlights• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? þ During cardiac surgery, myocardial ischemia and reperfusion injury occurs, which is associated with worse patient outcome. The endogenous nucleoside adenosine increases intrinsic myocardial resistance against ischemia and reperfusion. In preclinical studies, ischemia-reperfusion injury can be reduced by drugs that increase the endogenous adenosine concentration, including the adenosine uptake inhibitor dipyridamole. WHAT QUESTION DID THIS STUDY ADDRESS? þ Whether this approach translates into reduced myocardial injury in the clinical setting in patients undergoing coronary artery bypass surgery is currently unknown. We now addressed this question in a double-blinded randomized placebo-controlled study in this patient group. WHAT THIS STUDY ADDS TO OUR KNOWLEDGE þ We showed that pretreatment with dipyridamole did not reduce myocardial injury, as assessed by postoperative plasma troponin levels. Our results, therefore, demonstrate that, in contrast to preclinical studies, dipyridamole cannot be used to limit myocardial injury during cardiac surgery in the clinical setting. HOW THIS MIGHT CHANGE CLINICAL PHARMACOLOGY AND THERAPEUTICS þ These findings fuel the continuing search for pharmacological strategies aimed at improving patient outcomes in the setting of myocardial ischemia.

Association of early elevated cardiac troponin I concentration and longitudinal change after off-pump coronary artery bypass grafting and adverse events: a prospective cohort study

“…Association of early elevated cardiac troponin I concentration and longitudinal change after off-pump coronary artery bypass grafting and adverse events: a prospective cohort study complications after CABG is important to perform timely therapeutic strategies, such as more aggressive medication, urgent re-exploration of the graft with or without redo revascularization (CABG or percutaneous intervention), and mechanical circulation assist (intra-aortic balloon pump), to reduce the risk of morbidity. Cardiac troponin is the most frequently used biomarker for detecting myocardial injury and cardiac dysfunction after CABG, and elevation of troponin levels within the first 24 hours is independently associated with worse outcomes (3,4). Several studies have been performed to investigate the association between postoperatively elevated troponin concentration and the risk of complications; nevertheless, there were some limitations.…”

High Dose Meclizine Prevents Renal Ischemia–Reperfusion Injury in Healthy Male Mice

“…Nevertheless, evidence-based clinical management to prevent renal injury is still limited to optimization of organ perfusion and prevention of exposure to drugs that are toxic to the hypo-perfused kidney (i.e. aminoglycosides, NSAIDs and inhibitors of the renin-angiotensin-aldosterone system) because clinical trials exploring other strategies to prevent ischemia–reperfusion injury are not conclusive or negative ( Zuk and Bonventre 2015, EL MESSAOUDI et al 2015b, EL MESSAOUDI et al 2015a, ROSS et al 2005 ). Thus, the conclusion is justified that, at least up to now, strategies that prevent ischemia–reperfusion injury in pre-clinical models are stuck in translation to the clinic ( RONGEN and WEVER 2015 ).…”