Ziprasidone treatment was associated with a significantly greater mean QTc length (P=0.02) but a lower mean Tpe/QTc ratio (P<0.01) compared to non-ziprasidone-treated patients.
Observational (n=60)
Single-blind
Do antipsychotic drugs like ziprasidone alter 24-hour measures of QTc, Tpe, and Tpe/QTc in patients with schizophrenia compared to controls?
The large 24-hour variability in repolarization metrics suggests that QTc alone is insufficient to capture TdP risk, and 24-hour Holter monitoring may be necessary.
p-value: p=0.02
PURPOSE/BACKGROUND: Prolonged ventricular repolarization, measured by heart rate-corrected QT interval (QTc) prolongation, might be a biomarker for risk of torsade de pointes (TdP) and sudden cardiac death. However, the predictive value of QTc has been challenged, and a component of QTc, peak-to-end of the T-wave (Tpe), and a high Tpe/QT ratio might be superior biomarkers because they better reflect increased transmural dispersion of ventricular myocyte repolarization, which can lead to TDP. The purpose of this pilot study was to provide the first measurements of heart rate, QTc, Tpe, Tpe/QTc, and their variability over 24 hours in medication-free patients with schizophrenia, during treatment with ziprasidone or other antipsychotic drugs, and healthy controls. METHODS: Subjects included 12 patients treated with ziprasidone, 30 treated with other antipsychotic drugs, 3 unmedicated patients, and 15 normal controls. Subjects underwent 24-hour analog Holter recording, and the recordings were digitized. A cardiologist blind to treatment selected multiple 10-cycle segments throughout each recording and measured the electrocardiogram metrics. RESULTS: Variability in QTc, Tpe, and Tpe/QTc over the 24 hours was present in all groups; 91.1% of patients and 100% of controls had 1 or more QTc values of 450 milliseconds or greater. Mean QTc length was significantly greater in the ziprasidone-treated than the non-ziprasidone-treated patients (P = 0.02). Mean Tpe was not elevated in the ziprasidone patients, whereas mean Tpe/QTc was lower (P < 0.01). CONCLUSIONS: The large variability in QTc, Tpe, and Tpe/QTc observed supports the need for 24-hour electrocardiogram recordings to provide an accurate assessment of risk of TdP. Heart rate-corrected QT interval alone does not capture the risk of TdP.
Tümüklü et al. (Wed,) conducted a observational in Schizophrenia (n=60). Ziprasidone vs. Other antipsychotic drugs, unmedicated patients, and healthy controls was evaluated on Mean QTc length (p=0.02). Ziprasidone treatment was associated with a significantly greater mean QTc length (P=0.02) but a lower mean Tpe/QTc ratio (P<0.01) compared to non-ziprasidone-treated patients.