Hypothetical interventions on emergency ambulance and prehospital acetylsalicylic acid administration in myocardial infarction patients presenting without chest pain

BACKGROUND: Myocardial infarction (MI) patients presenting without chest pain are a diagnostic challenge. They receive suboptimal prehospital management and have high mortality. To elucidate potential benefits of improved management, we analysed expected outcome among non-chest pain MI patients if hypothetically they (1) received emergency ambulances/acetylsalicylic acid (ASA) as often as observed for chest pain patients, and (2) all received emergency ambulance/ASA. METHODS: We sampled calls to emergency and non-emergency medical services for patients hospitalized with MI within 24 h and categorized calls as chest pain/non-chest pain. Outcomes were 30-day mortality and a 1-year combined outcome of re-infarction, heart failure admission, and mortality. Targeted minimum loss-based estimation was used for all statistical analyses. RESULTS: Among 5418 calls regarding MI patients, 24% (1309) were recorded with non-chest pain. In total, 90% (3689/4109) of chest pain and 40% (525/1309) of non-chest pain patients received an emergency ambulance, and 73% (2668/3632) and 37% (192/518) of chest pain and non-chest pain patients received prehospital ASA. Providing ambulances to all non-chest pain patients was not associated with improved survival. Prehospital administration of ASA to all emergency ambulance transports of non-chest pain MI patients was expected to reduce 30-day mortality by 5.3% (CI 95%: [1.7%;9%]) from 12.8% to 7.4%. No significant reduction was found for the 1-year combined outcome (2.6% CI 95% [− 2.9%;8.1%]). In comparison, the observed 30-day mortality was 3% among ambulance-transported chest pain MI patients. CONCLUSIONS: Our study found large differences in the prehospital management of MI patients with and without chest pain. Improved prehospital ASA administration to non-chest pain MI patients could possibly reduce 30-day mortality, but long-term effects appear limited. Non-chest pain MI patients are difficult to identify prehospital and possible unintended effects of ASA might outweigh the potential benefits of improving the prehospital management. Future research should investigate ways to improve the prehospital recognition of MI in the absence of chest pain. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12872-022-03000-1

Estimation of time-specific intervention effects on continuously distributed time-to-event outcomes by targeted maximum likelihood estimation

Targeted maximum likelihood estimation is a general methodology combining flexible ensemble learning and semiparametric efficiency theory in a two-step procedure for estimation of causal parameters. Proposed targeted maximum likelihood procedures for survival and competing risks analysis have so far focused on events taken values in discrete time. We here present a targeted maximum likelihood estimation procedure for event times that take values in R+. We focuson the estimation of intervention-specific mean outcomes with stochastic interventions on a time-fixed treatment. For data-adaptive estimation of nuisance parameters, we propose a new flexible highly adaptive lasso estimation method for continuous-time intensities that can be implemented with L1-penalized Poisson regression. In a simulation study the targeted maximum likelihood estimator based on the highly adaptive lasso estimator proves to be unbiased and achieve proper coverage in agreement with the asymptotic theory and further displays efficiency improvements relative to a Kaplan-Meier approach