The cardiac safety of aripiprazole treatment in patients at high risk for torsade: a systematic review with a meta-analytic approach
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The cardiac safety of aripiprazole treatment in patients at high risk for torsade : a systematic review with a meta-analytic approach. / Polcwiartek, Christoffer; Sneider, Benjamin; Graff, Claus; Taylor, David; Meyer, Jonathan; Kanters, Jørgen K.; Nielsen, Jimmi.
In: Psychopharmacology, Vol. 232, No. 18, 09.2015, p. 3297-308.Research output: Contribution to journal › Review › Research › peer-review
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TY - JOUR
T1 - The cardiac safety of aripiprazole treatment in patients at high risk for torsade
T2 - a systematic review with a meta-analytic approach
AU - Polcwiartek, Christoffer
AU - Sneider, Benjamin
AU - Graff, Claus
AU - Taylor, David
AU - Meyer, Jonathan
AU - Kanters, Jørgen K.
AU - Nielsen, Jimmi
PY - 2015/9
Y1 - 2015/9
N2 - 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.
AB - 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.
KW - Antipsychotic Agents
KW - Aripiprazole
KW - Arrhythmias, Cardiac
KW - Death, Sudden, Cardiac
KW - Electrocardiography
KW - Heart
KW - Heart Conduction System
KW - Heart Rate
KW - Humans
KW - Long QT Syndrome
KW - Potassium
KW - Risk Factors
KW - Safety
KW - Torsades de Pointes
U2 - 10.1007/s00213-015-4024-9
DO - 10.1007/s00213-015-4024-9
M3 - Review
C2 - 26231497
VL - 232
SP - 3297
EP - 3308
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 18
ER -
ID: 161341838