Lidocaine was not noninferior to fentanyl for reducing ischemic chest pain but was better tolerated during emergency transport to the hospital among patients with suspected ST-segmental elevation myocardial infarction (STEMI). These findings from a prospective, phase 2, open-label, noninferiority, randomized trial were published in the European Heart Journal of Acute Cardiovascular Care.
The lidocAine Versus Opioids In MyocarDial Infarction (AVOID-2) trial assessed outcomes among possible STEMI patients requiring emergency transport to Monash University in Australia in 2020 and 2021. Patients (N=308) with suspected ST-segment elevation acute coronary syndrome with numerical rating scale (NRS) pain scores of 5 or greater were randomly assigned to receive 50 to 100 mg intravenous (IV) lidocaine depending on weight with an additional 50 to 100 mg every 15 minutes as required (n=154) or up to 50 μg IV fentanyl every 5 minutes as required (n=154) during emergency transport. The co-primary endpoints were median reduction in pain based on verbal NRS scores and adverse drug reactions. Noninferiority was defined using the 95% CI bounds with the lower bound defining efficacy and the upper bound defining safety.
Mean ages of participants in the lidocaine and fentanyl cohorts were 62 (standard deviation [SD], 12) and 60 (SD, 12) years, 82% and 81% were men, 51% and 48% had hypertension, and 44% and 45% had dyslipidemia, respectively.
During transport to the hospital, the mean initial pain score was 8 points for both cohorts. The fentanyl recipients had significantly lower pain scores at hospital arrival (median, 3 vs 4; P =.001), more had an NRS score of 0 to 4 at arrival (68% vs 54%; P =.01), more experienced a 1 point or greater reduction in NRS pain score after treatment (93% vs 79%; P =.001), and more experienced a 2 point or greater reduction in NRS pain score point after treatment (86% vs 72%; P =.002) compared with recipients of lidocaine, respectively.
Recipients of fentanyl, however, experienced significantly higher rates of nausea or vomiting requiring intervention with ondansetron or metoclopramide (44% vs 28%; P =.003) compared with lidocaine recipients, respectively.
Lidocaine recipients had numerically more tinnitus and tongue paresthesia events. Fentanyl recipients had numerically more incidences of reduced Glasgow coma scale score requiring intervention, bradyarrhythmia requiring intervention, atropine use, and hypoxia events compared with recipients of lidocaine; however, none of these rates were statistically significantly different.
Most patients underwent percutaneous coronary intervention (PCI) for STEMI (84% of those receiving lidocaine and 83% of those receiving fentanyl). The duration of time from symptom to intervention was 142 and 141 minutes, and door-to-balloon time was 47 and 51 minutes for the lidocaine and fentanyl cohorts, respectively.
Neither in-hospital nor 30-day outcomes differed among patients who underwent primary PCI on the basis of fentanyl or lidocaine receipt during emergency transport to the hospital. Similarly, no trends in cardiac magnetic resonance imaging outcomes were reported.
A major limitation of this study was the lack of blinding of the paramedics who administered lidocaine or fentanyl treatments and assessed verbal pain scores.
These data indicate that lidocaine was not as effective as fentanyl for reducing chest pain during emergency transport to the hospital among patients with suspected STEMI. However, lidocaine was associated with a superior safety profile compared with fentanyl. The authors conclude, “We await future studies that investigate whether use of nonopioid analgesics leads to improved clinical outcomes by avoiding a drug interaction with oral P2Y12 inhibitors.”
Fernando H, Nehme Z, Milne C, et al; AVOID 2 Investigators. LidocAine Versus Opioids In MyocarDial infarction: the AVOID-2 randomised controlled trial. Eur Heart J Acute Cardiovasc Care. Published online December 10, 2022. doi:10.1093/ehjacc/zuac154