Department of Biostatistics and Epidemiology, the Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, 19104-6021, USA.
Am J Psychiatry. 2011 Feb;168(2):193-201. doi: 10.1176/appi.ajp.2010.08040484. Epub 2010 Nov 1.
The authors compared 1-year mortality rates associated with ziprasidone and olanzapine in real-world use.
The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) was an open-label, randomized, postmarketing large simple trial that enrolled patients with schizophrenia (N=18,154) in naturalistic practice in 18 countries. The primary outcome measure was nonsuicide mortality in the year after initiation of assigned treatment. Patients were randomly assigned to receive treatment with either ziprasidone or olanzapine and followed for 1 year by unblinded investigators providing usual care. A physician-administered questionnaire was used to collect baseline demographic information, medical and psychiatric history, and concomitant medication use. Follow-up information on hospitalizations and emergency department visits, patients' vital status, and current antipsychotic drug status was collected and reported by treating psychiatrists. Post hoc analyses of sudden death, a secondary endpoint, were also conducted.
The incidence of nonsuicide mortality within 1 year of initiating pharmacotherapy was 0.91 for ziprasidone (N=9,077) and 0.90 for olanzapine (N=9,077). The relative risk was 1.02 (95% CI=0.76-1.39). This finding was confirmed in numerous secondary and sensitivity analyses.
Despite the known risk of QTc prolongation with ziprasidone treatment, the findings of this study failed to show that ziprasidone is associated with an elevated risk of nonsuicidal mortality relative to olanzapine in real-world use; the study excludes a relative risk larger than 1.39 with a high probability. However, the study was neither powered nor designed to examine the risk of rare events like torsade de pointes.
作者比较了在真实环境中使用齐拉西酮和奥氮平的 1 年死亡率。
齐拉西酮观察性心脏结局研究（ZODIAC）是一项开放标签、随机、上市后大型简单试验，在 18 个国家的自然环境中招募了精神分裂症患者（N=18154）。主要结局指标是起始治疗后 1 年内非自杀性死亡率。患者被随机分配接受齐拉西酮或奥氮平治疗，并由未设盲的研究者提供常规护理，随访 1 年。采用医生管理的问卷收集基线人口统计学信息、医疗和精神病史以及同时使用的药物。通过治疗精神科医生收集和报告关于住院和急诊就诊、患者的生命状态和当前抗精神病药物状态的随访信息。还进行了次要终点猝死的事后分析。
起始药物治疗后 1 年内非自杀性死亡率，齐拉西酮为 0.91（N=9077），奥氮平为 0.90（N=9077）。相对风险为 1.02（95%CI=0.76-1.39）。这一发现在许多次要和敏感性分析中得到了证实。
尽管已知齐拉西酮治疗与 QTc 延长有关，但这项研究的结果并未表明在真实环境中，齐拉西酮与奥氮平相比，非自杀性死亡率的风险升高；该研究极有可能排除相对风险大于 1.39 的情况。然而，该研究既没有足够的效力也没有设计来检查罕见事件（如尖端扭转型室速）的风险。
