The cardiac safety of aripiprazole treatment in patients at high risk for torsade: A systematic review with a meta-analytic approach

Rationale: Certain antipsychotics increase the risk of heart rate-corrected QT (QTc) prolongation and consequently Torsades de Pointes (TdP) and sudden cardiac death (SCD). Drug-induced Brugada syndrome (BrS) is also associated with SCD. Most SCDs occur in patients with additional cardiac risk factors. Objectives: Aripiprazole's cardiac safety has not been assessed in patients at high risk for torsade, where QTc prolongation risk is highly increased. Methods: MEDLINE, Embase, and The Cochrane Library were searched for preclinical, clinical, and epidemiological studies. Eligible studies were reviewed and cardiac safety data were extracted. Continuous and dichotomous QTc data were used in the meta-analysis. Results: Preclinical studies suggested that aripiprazole has limited affinity for the delayed rectifier potassium current. TdP was reported in two case reports and SCD was reported in one case report and one case series. No clinical studies assessing aripiprazole's cardiac safety in patients at high risk for torsade were found. No thorough QT (TQT) study with aripiprazole was found. The meta-analysis revealed that the mean ΔQTc interval was decreased with aripiprazole and QTc prolongation risk was lower compared with placebo and active controls. Epidemiological studies linked aripiprazole to weak/moderate torsadogenicity. No studies were found associating aripiprazole with BrS suggesting low affinity for the fast sodium current. Conclusions: Aripiprazole is a low-risk antipsychotic regarding cardiac safety in healthy patients. However, baseline and steady state electrocardiogram is recommended in patients at high risk for torsade due to marked QTc prolongation, absence of a TQT study, and lack of data in this group.