A 'Target Trial Emulation' of Prehospital Sublingual Nitroglycerin Administration for Suspected Acute Coronary...

Prehospital clinicians administer sublingual nitroglycerin to hundreds of thousands of patients per year in the United States for suspected acute coronary syndrome (ACS), but the effects of this intervention have not been thoroughly studied. We aimed to estimate the association between nitroglycerin administration and prehospital outcomes using a nationwide dataset.

We evaluated all patients in the ESO Data Collaborative 2023 annual dataset with an EMS clinician primary impression that suggested chest pain, ACS, or a myocardial infarction who received 324 or 325 milligrams of aspirin from emergency medical services (EMS) clinicians following a 9-1-1 call for inclusion. We excluded patients who were <50 years of age, had a pre-aspirin systolic blood pressure (SBP) <120 mmHg or no pre-aspirin SBP and heart rate documented, a pre-aspirin SpO2 < 90%, or pre-aspirin bronchodilator administration. We classified patients as receiving nitroglycerin if a dose was administered within 10 minutes after aspirin administration. To address both confounding and immortal time bias, we used clone-censor weighting to compare these groups using a composite outcome comprised of prehospital CPR, defibrillation, cardioversion, antiarrhythmic administration, or transcutaneous pacing. Our models included age, sex, race, initial pain score, minimum pre-ASA SBP, maximum pre-ASA heart rate, and prehospital documentation of a suspected ST-elevation myocardial infarction (STEMI). We reported all results as effect sizes with 95% confidence intervals at the 50^th, 75^th, and 90^th percentile of follow-up time (17, 26, and 35 min).

We analyzed 70,890 patients (34,887 (49%) nitroglycerin) from 2,119 EMS agencies. Overall, 139 (0.2%) patients experienced our composite outcome. Nitroglycerin administration was not associated with a significant decrease in the composite outcome at any timepoint following administration of aspirin overall (17 min: -0.02% (-0.08, +0.05); 26 min: -0.05% (-0.15, +0.06); 35 min: -0.10% (-0.30, +0.10)) or among the subgroup of patients with suspected STEMI.

Nitroglycerin administration in the setting of suspected ACS was not associated with a reduction in our composite outcome in the prehospital setting. These analyses were limited by the low prevalence of our outcome and the retrospective, observational nature of these data.