Comparative cardiac safety of haloperidol vs. chlorpromazine among people receiving hemodialysis

Background

Sudden cardiac death (SCD) is > 20 times more likely among individuals receiving maintenance hemodialysis, relative to individuals not receiving hemodialysis. Typical antipsychotics increase risk for QT prolongation and SCD in the general population. The comparative cardiac safety of typical antipsychotics among individuals receiving hemodialysis is unknown.

Methods

This cohort study used an active comparator, new-user design to examine relative cardiac safety of the most frequently prescribed oral typical antipsychotics among individuals receiving outpatient maintenance hemodialysis (2007–2019). Data were obtained from the U.S Renal Data System. The primary outcome was 1-year risk of SCD. Inverse probability of treatment weighted Fine and Gray models estimated adjusted hazard ratios (aHR) and adjusted risk differences (aRDs), with 95 % confidence intervals (CIs), using an intention-to-treat approach. In primary analyses, deaths due to causes other than SCD were competing events.

Results

Among 846,400 maintenance hemodialysis patients (2007–2019), haloperidol (n = 10,813) and chlorpromazine (n = 5800) were the most commonly prescribed oral typical antipsychotics. Among 6266 haloperidol and 3959 chlorpromazine new-users, 662 (9.9 %) and 234 (5.9 %), respectively, experienced SCD by 1-year. Compared to chlorpromazine new-use, Haloperidol new-use was associated with higher 1-year risk of SCD, aHR (95 % CI) = 1.38 (1.21,1.59); aRD (95 % CI) = 2.62 % (−0.27 %, 5.51 %). Analyses of additional cardiac outcomes yielded similar findings.

Conclusions

Haloperidol was the most prescribed oral typical antipsychotic. Haloperidol new-use associated with a higher 1-year risk of SCD and other adverse cardiac outcomes compared to chlorpromazine new-use. Caution and close monitoring are warranted when newly prescribing haloperidol to individuals receiving hemodialysis.