Haloperidol Associated With Slight Increased Risk for Death in Acute Myocardial Infarction

Findings published in the British Medical Journal indicate a small increased risk for death within 7 days of initiating haloperidol compared with initiating an atypical antipsychotic medication for patients with acute myocardial infarction.

Researchers conducted a healthcare database cohort study that included 6578 patients (mean age 75.2 years) with a primary diagnosis of acute myocardial infarction who initiated oral haloperidol or oral atypical antipsychotic medication during a hospital admission between 2003 and 2014. Of these patients, 1668 (25.4%) individuals received oral haloperidol and 4910 (74.6%) received oral atypical antipsychotic medications during their inpatient stay. 

In the first week after treatment initiation, death occurred in 129 (7.8%) of those taking haloperidol and in 92 (5.5%) of those taking atypical antipsychotic medications, for an absolute death rate per 100 person-days of 1.7 and 1.1, respectively.

Researchers matched patients receiving an atypical antipsychotic medication with patients receiving haloperidol (1:1) and performed intention-to-treat analyses from the initial exposure to the end of follow-up. At day 7, the survival probability was 0.93 in patients using haloperidol and 0.94 in patients using atypical antipsychotic medications. The adjusted hazard ratio (HR; 95% CI) in the matched cohort was 1.50 (1.14-1.96). The association between haloperidol use and death risk was strongest during the first 4 days of follow-up and decreased over time. By day 5, the increased risk was no longer evident (HR 1.12; 95% CI, 0.79-1.59). Haloperidol was associated with an increased risk for death compared with olanzapine (HR 1.59; 95% CI, 1.13-2.24), quetiapine (HR 1.79; 95% CI, 1.33-2.41), and risperidone (HR 1.51; 95% CI, 1.12-2.03).

The mean follow-up was 2.8 (SD 1.7) days for haloperidol initiators and 3.7 (2.1) days for atypical antipsychotic medication initiators; the interaction coefficient for duration of follow-up by drug use was statistically significant (P =.008). Researchers acknowledged that the shorter treatment duration for haloperidol compared with atypical antipsychotic medications may have created a differential censoring bias, but they emphasized that sensitivity analyses showed consistent effects. As such, these data may be useful to clinicians in considering the risks and benefits of prescribing haloperidol for patients with cardiac morbidity. 

Reference

Park Y, Bateman BT, Kim DH, et al. Use of haloperidol versus atypical antipsychotics and risk of in-hospital death in patients with acute myocardial infarction: cohort study. BMJ. 2018;360:k1218.