PracticeUpdate: Cardiology - Winter 2018

EDITOR’S PICKS 13

Epinephrine vs Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction JACC: Journal of the American College of Cardiology

RESULTS Fifty-seven patients were randomized into 2 study arms, epinephrine and norepineph- rine. For the primary efficacy endpoint, cardiac index evolution was similar between the 2 groups (p = 0.43) from baseline (H0) to H72. For the main safety endpoint, the observed higher incidence of refractory shock in the epineph- rine group (10 of 27 [37%] vs. norepinephrine 2 of 30 [7%]; p = 0.008) led to early termination of the study. Heart rate increased significantly with epinephrine from H2 to H24 while remain- ing unchanged with norepinephrine (p < 0.0001). Several metabolic changes were unfavorable to epinephrine compared with norepinephrine, including an increase in cardiac double prod- uct (p = 0.0002) and lactic acidosis from H2 to H24 (p < 0.0001). CONCLUSIONS In patients with CS secondary to acute myocardial infarction, the use of epi- nephrine compared with norepinephrine was associated with similar effects on arterial pres- sure and cardiac index and a higher incidence of refractory shock. Epinephrine Versus Norepinephrine for Cardio- genic Shock After Acute Myocardial Infarction. J Am Coll Cardiol 2018 Jul 10;72(2)173-182, B Levy, R Clere-Jehl, A Legras, et al. www.practiceupdate.com/c/70550 optimal management strategies for this phenotypically and hemodynamically diverse and deadly condition. At this time, if faced with a choice for your patient with CS, it would seem that norep- inephrine may be a more preferred initial vasoactive medication. More importantly, however, is that the treating physician understands the unique pathophysiology of his/her patient and the unique phar- macology of each drug, and then closely and systematically monitors the clinical response of the patient to therapy.

Take-home message • This is a prospective, multicenter, double-blind study comparing 57 patients randomized to receive epinephrine or norepinephrine for cardiogenic shock following an acute myocardial infarction (AMI). Based on a comparison of cardiac index evolution using an intention-to-treat analysis, efficacywas not statistically different between the two groups frombaseline (H0) to H72. Because a higher incidence of refractory shock occurred in the epinephrine group (37%of patients comparedwith 7%of the norepinephrine group), the study was terminated prematurely. There was a significant increase in heart rate fromH2 toH24 in the epinephrine group only. Additionally, increases in cardiac double product and in lactic acidosis fromH2 to H24 occurred only in the epinephrine group. • Although this study included a relatively small number of patients, it suggests that there is a higher risk of refractory shock in patients treated with epinephrine compared with norepinephrine. However, the authors note that different patterns may be present in cardiogenic shock with etiologies other than AMI. Abstract

BACKGROUND Vasopressor agents could have certain specific effects in patients with cardio- genic shock (CS) after myocardial infarction, which may influence outcome. Although nor- epinephrine and epinephrine are currently the most commonly used agents, no randomized trial has compared their effects, and interven- tion data are lacking. OBJECTIVES The goal of this paper was to com- pare in a prospective, double-blind, multicenter, COMMENT By Jason N. Katz MD, MHS C ardiogenic shock (CS) is complicated. It is difficult to define, diverse in its etiology and presentation, and chal- lenging tomanage. Despite the fact that we have found ways – mechanical and phar- macologic – to rapidly re-perfuse coronary arteries and favorably alter the natural his- tory of myocardial infarction (MI), mortality in CS remains unacceptably high. No soci- ety-endorsed guidelines currently exist for the management of CS, and recommenda- tions crafted by key opinion leaders rest precariously upon a very tenuous evidence base. The paper by Levy and colleagues is another in a series of small, but important, steps in helping to optimize care for these complex patients. In this prospective, mul- ticenter, double-blinded study, individuals with persistent CS (despite percutaneous coronary intervention) were randomized either to epinephrine or norepinephrine for vasoactive support. There were no differences in the majority of collected hemodynamic endpoints (including cardiac

randomized study, the efficacy and safety of epi- nephrine and norepinephrine in patients with CS after acute myocardial infarction. METHODS The primary efficacy outcome was cardiac index evolution, and the primary safety outcome was the occurrence of refractory CS. Refractory CS was defined as CS with sustained hypotension, end-organ hypoperfusion and hyper- lactatemia, and high inotrope and vasopressor doses.

index, stroke volume index, andmean arte- rial pressure) and no differences in death, the use of additional inotropic therapies, or the employment of mechanical circulatory support. There was, however, a greater increase in heart rate and serum lactate with the use of epinephrine, along with a greater incidence of refractory CS. This was clearly a difficult trial to con- duct. Despite a targeted sample size of 80 patients, only 57 were enrolled over a 4-year period at 9 participating centers. The trial was stopped early due to higher rates of refractory CS in the epinephrine-treated group – a safety endpoint (it is important to emphasize) that was not prespecified. Although not necessarily practice-changing, there is certainly a lot to glean from this study. The findings provide important mecha- nistic insights into the use of vasoactive medications for CS. It also should compel the cardiovascular community to intensify collaborative efforts focused on defining

Dr. Katz is Associate Professor of Medicine, Medical Director for the Cardiac Intensive Care Unit, Cardiothoracic Surgical Intensive Care Unit, and Mechanical Heart Program, and Director of Cardiovascular Clinical Trials at University of North Carolina School of Medicine in Chapel Hill, North Carolina.

VOL. 3 • NO. 3 • 2018