Effect and Safety of Morphine Use in Acute Anterior ST‐Segment Elevation Myocardial Infarction

Abstract

BackgroundMorphine is commonly used to treat chest pain during myocardial infarction, but its effect on cardiovascular outcome has never been directly evaluated. The aim of this study was to examine the effect and safety of morphine in patients with acute anterior ST‐segment elevation myocardial infarction followed up for 1 year.Methods and ResultsWe used the database of the CIRCUS (Does Cyclosporine Improve Outcome in ST Elevation Myocardial Infarction Patients) trial, which included 969 patients with anterior ST‐segment elevation myocardial infarction, admitted for primary percutaneous coronary intervention. Two groups were defined according to use of morphine preceding coronary angiography. The composite primary outcome was the combined incidence of major adverse cardiovascular events, including cardiovascular death, heart failure, cardiogenic shock, myocardial infarction, unstable angina, and stroke during 1 year. A total of 554 (57.1%) patients received morphine at first medical contact. Both groups, with and without morphine treatment, were comparable with respect to demographic and periprocedural characteristics. There was no significant difference in major adverse cardiovascular events between patients who received morphine compared with those who did not (26.2% versus 22.0%, respectively; P=0.15). The all‐cause mortality was 5.3% in the morphine group versus 5.8% in the no‐morphine group (P=0.89). There was no difference between groups in infarct size as assessed by the creatine kinase peak after primary percutaneous coronary intervention (4023±118 versus 3903±149 IU/L; P=0.52).ConclusionsIn anterior ST‐segment elevation myocardial infarction patients treated by primary percutaneous coronary intervention, morphine was used in half of patients during initial management and was not associated with a significant increase in major adverse cardiovascular events at 1 year.

Impact of Morphine Treatment on Infarct Size and Reperfusion Injury in Acute Reperfused ST-Elevation Myocardial Infarction

“…Patients with not completely occluded vessels (TIMI flow ≥I) may develop smaller infarct size, regardless of protection strategy and this may also influence the cardioprotective effect of morphine. These findings are in accordance with evidence that opioid agonists may be involved in favorable cardioprotective effects on the myocardium [13][14][15][16][17][18]28]. In animal models of myocardial reperfusion injury, morphine preconditioning improved cardiac function and reduced post-infarction remodeling [15,[28][29][30].…”

“…The interaction between morphine and P2Y12 inhibitors has been proposed to explain, at least in part, the adverse outcomes, as demonstrated by impaired ST-segment resolution in patients with STEMI in the ATLANTIC trial [26]. On the other hand, in the FAST-MI 2010 cohort and in a sub-analysis of the CIRCUS trial, morphine was not associated with a higher risk of clinical events, including death and stent thrombosis [17,27]. The lack of randomized studies with clinical endpoints precludes drawing final conclusions regarding morphine use and clinically significant effects on patient outcomes.…”

“…However, previous studies reported inconsistent results regarding the effect of morphine on myocardial damage in patients with acute myocardial infarction [15][16][17][18] and were mainly limited by preclinical studies, non-randomized observational study designs, as well as the assessment of indirect parameters of reperfusion success, like ST-segment resolution, TIMI flow grade after PPCI or infarct size measurement by biomarkers. Our results support a potential cardioprotective effect of morphine in patients with early reperfusion, but larger randomized studies are needed to finally elucidate the true clinical significance on hard clinical outcomes.…”

“…In contrast, there is also evidence that opioid agonists may be involved in favorable cardioprotective effects on the myocardium, with beneficial effects on all major determinants of ischemia-reperfusion injury (infarction/apoptosis, arrhythmogenesis, contractile dysfunction, inflammation) [12][13][14]. However, previous studies reported inconsistent results regarding the effect of morphine on myocardial damage in patients with acute myocardial infarction [15][16][17][18] and had several limitations including single-center design, small sample size, and indirect infarct size assessment. Cardiac magnetic resonance (CMR) imaging is the reference standard technique for the assessment of infarct size and reperfusion injury [19].The aim of this study was to comprehensively evaluate the impact of morphine treatment on infarct size and reperfusion injury assessed by CMR in an adequately-sized multicenter study of patients with acute STEMI undergoing PPCI.…”

Impact of Preadmission Morphine on Reinfarction in Patients With ST‐Elevation Myocardial Infarction Treated With Percutaneous Coronary Intervention: A Meta‐Analysis

“…Of these, two studies were excluded since only infarct size, based on cardiac magnetic resonance imaging, was reported as an outcome; a further study was excluded since it included a mixed group of patients with both STEMI and non‐ST elevation ACS where STEMI data could not be extricated; and another study was excluded as it included only patients with non‐ST elevation ACS . A further 17 studies were excluded for not reporting the clinical outcome of interest …”