Clinical outcomes of chest pain with cocaine use: a propensity score-matched analysis

Cocaine use has been linked to cardiovascular complications due to its vasoconstrictive properties; however, short-term risk of major adverse cardiac events (MACE) in patients presenting with chest pain remains controversial due to limited sample sizes (< 5000 patients). Leveraging the TriNetX database, we analyzed 89,652 patients, providing the largest and most statistically powered evaluation of cocaine-associated chest pain to date. This retrospective, propensity score-matched cohort study used the TriNetX Research Network to identify adults presenting to the ED with chest pain or shortness of breath (March 2005-March 2025). Patients undergoing urine toxicology were matched 1:1 into + COCN and -COCN cohorts. The primary outcome was 30-day composite MACE, including acute myocardial infarction (AMI), acute decompensated heart failure (ADHF), ischemic stroke, and cardiac arrest. The matched cohorts included 44,826 patients each. The + COCN group had statistically higher rates of MACE components, though absolute differences were small: AMI (1.25% vs. 0.30%; Risk Difference [RD] 0.002), ADHF (0.17% vs. 0.07%; RD 0.001), and ischemic stroke (0.32% vs. 0.14%; RD 0.002) (all p < 0.001). Cardiac arrest was also more frequent (0.14% vs. 0.09%; p = 0.04). Initial troponin I levels were comparable (+ COCN: 0.3 ± 3.2 ng/mL vs. -COCN: 0.7 ± 4.7 ng/mL, p < 0.001).Cocaine positivity in ED chest pain patients was not associated with a clinically meaningful increase in 30-day MACE. These findings support incorporating + COCN patients into standard, risk-based chest pain pathways rather than reflexive admission or over-testing.