Treatment of Chest Pain in Acute Coronary Syndromes

abstract & commentary

Source: Baumann BM, et al. Randomized, double-blind, placebo-controlled trial of diazepam, nitroglycerin, or both for treatment of patients with potential cocaine-associated acute coronary syndromes. Acad Emerg Med 2000;7:878-885.

This trial from the university of pennsylvania is the first study to compare different treatment modalities in symptomatic patients with potential cocaine-associated acute coronary syndromes. Patients with cocaine-induced chest pain were randomized to treatment with 5 mg diazepam intravenously, 0.4 mg nitroglycerin sublingually, or both every 5 minutes for 15 minutes, or until resolution of symptoms. Inclusion criteria included: age between 18 and 60 years, cocaine use within 24 hours, history suggestive of ischemic chest pain, and the ability to provide informed consent. Major outcomes were reduction in chest pain (measured by visual analog scale), changes in blood pressure and heart rate, and change in stroke index (measured with a transthoracic cardiac output monitor). Forty patients were enrolled (diazepam 12; nitroglycerin 13; both 15). Baseline demographics, cocaine use, chest pain characteristics, initial ECGs, and discharge diagnoses were similar among the three groups.

Chest pain reduction was similar among the three groups (diazepam, -33.3 ± 8.0 mm; nitroglycerin, -30.7 ± 7.1 mm; both, -33.0 ± 7.9 mm; P = 0.6). There were no significant differences in heart rate and blood pressure changes among the treatment groups. Stroke index de-creased during treatment for all groups (diazepam, -8.7 ± 3.3; nitroglycerin, -3.1 ± 2.8; both, -1.8 ± 3.1; P = 0.03), but was not statistically significant after adjustment for multiple comparisons. The authors conclude that chest pain resolution and changes in cardiac performance do not differ for patients with potential cocaine-associated acute coronary syndromes when treated with diazepam or nitroglycerin. They also conclude that use of both agents did not offer any advantage over use of either agent alone.

COMMENT BY JACOB W. UFBERG, MD

Cocaine may cause myocardial ischemia through several mechanisms. It causes tachycardia and hypertension leading to increased myocardial oxygen demand, and causes alpha-adrenergic mediated coronary artery vasoconstriction, among other effects. It is believed that central nervous system (CNS) stimulation may exacerbate the peripheral effects of cocaine, and that blockade of CNS stimulation with benzodiazepines may prevent some of the peripheral sympathomimetic effects of the drug, thus decreasing myocardial oxygen demand. Nitroglycerin has been shown to reverse cocaine-induced coronary artery vasoconstriction and relieve cocaine-induced chest pain. Its effects on mortality and infarct size have been proven in traditional patients with acute myocardial infarction, although they have not been studied in a cocaine-induced chest pain population.

This well-executed study is the first randomized, prospective clinical trial comparing these two treatment modalities. The only apparent limitations of the study lie in the small sample sizes. The authors also acknowledge a larger-than-expected standard deviation, which further reduces the study’s ability to detect a difference between groups. Even so, the authors’ conclusions appear valid. Diazepam and nitroglycerin performed equivalently in the treatment of potential cocaine-induced acute coronary syndromes, while combination therapy offered no additional benefit. Physicians may wish to choose their treatment based on the presence or absence of hypertension, tachycardia, and CNS excitation.