Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study

OBJECTIVE To compare the risk of in-hospital mortality associated with haloperidol compared with atypical antipsychotics in patients admitted to hospital with acute myocardial infarction. DESIGN Cohort study using a healthcare database. SETTING Nationwide sample of patient data from more than 700 hospitals across the United States. PARTICIPANTS 6578 medical patients aged more than 18 years who initiated oral haloperidol or oral atypical antipsychotics (olanzapine, quetiapine, risperidone) during a hospital admission with a primary diagnosis of acute myocardial infarction between 2003 and 2014. MAIN OUTCOME MEASURE In-hospital mortality during seven days of follow-up from treatment initiation. RESULTS Among 6578 patients (mean age 75.2 years) treated with an oral antipsychotic drug, 1668 (25.4%) initiated haloperidol and 4910 (74.6%) initiated atypical antipsychotics. The mean time from admission to start of treatment (5.3 v 5.6 days) and length of stay (12.5 v 13.6 days) were similar, but the mean treatment duration was shorter in patients using haloperidol compared with those using atypical antipsychotics (2.4 v 3.9 days). 1:1 propensity score matching was used to adjust for confounding. In intention to treat analyses with the matched cohort, the absolute rate of death per 100 person days was 1.7 for haloperidol (129 deaths) and 1.1 for atypical antipsychotics (92 deaths) during seven days of follow-up from treatment initiation. The survival probability was 0.93 in patients using haloperidol and 0.94 in those using atypical antipsychotics at day 7, accounting for the loss of follow-up due to hospital discharge. The unadjusted and adjusted hazard ratios of death were 1.51 (95% confidence interval 1.22 to 1.85) and 1.50 (1.14 to 1.96), respectively. The association was strongest during the first four days of follow-up and decreased over time. By day 5, the increased risk was no longer evident (1.12, 0.79 to 1.59). In the as-treated analyses, the unadjusted and adjusted hazard ratios were 1.90 (1.43 to 2.53) and 1.93 (1.34 to 2.76), respectively. CONCLUSION The results suggest a small increased risk of death within seven days of initiating haloperidol compared with initiating an atypical antipsychotic in patients with acute myocardial infarction. Although residual confounding cannot be excluded, this finding deserves consideration when haloperidol is used for patients admitted to hospital with cardiac morbidity.