Samizo Kazuo, Kawabe Eri, Hinotsu Shiro, Sato Tsugumichi, Kageyama Shigeru, Hamada Chikuma, Ohashi Yasuo, Kubota Kiyoshi
Department of Pharmacoepidemiology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Drug Saf. 2002;25(11):811-21. doi: 10.2165/00002018-200225110-00005.
Two pilot studies for prescription-event monitoring in Japan (J-PEM) were launched in 1997 and 1998. Here we present data regarding adverse events that were reported in the second pilot J-PEM study where losartan was compared with ACE inhibitors and dihydropyridine calcium channel antagonists.
We conducted a cohort study with a concurrent control. METHODS/PATIENT GROUP: Study subjects prescribed losartan, an ACE inhibitor or a calcium channel antagonist were identified from prescriptions in hospital or community pharmacies. Events and other information were collected from doctors and pharmacists by mailed questionnaires. Events were coded and analysed using the Medical Dictionary for Regulatory Activities (MedDRA) terminology. Crude event rates were calculated and compared between patients treated with losartan and those receiving control drugs. When the difference was statistically significant, the event was further examined in several ways, including follow-up studies and by comparison with the data of the UK PEM study on losartan.
Pharmacists were sent 4344 questionnaires and returned 3591 (83%), while doctors were sent 3517 questionnaires and returned 1380 (39%). In the doctors' data, the adverse event rate for losartan treatment was greater than that for ACE inhibitors and/or calcium channel antagonists for the following seven events: headache, palpitations, anaemia, insomnia, feeling abnormal, increased blood pressure and asthma. Most of these are known adverse drug reactions (ADRs) of losartan except for two events: increased blood pressure and asthma. In pharmacists' data, the event rate for losartan was significantly greater than that for control drugs for the following ten events: hot flushes, abnormal hepatic function, oedema, peripheral swelling, decreased blood pressure, increased blood pressure, rhinitis, contact dermatitis, dry skin and heat rash. The first five events were known ADRs of losartan but the other five were not. When the two sets of data were combined, the rate of an additional event, increased blood creatinine phosphokinase, which is a known ADR of losartan, was significantly greater than that for the control drugs. The six events that were not documented as ADRs for losartan were not judged to be ADRs based on the results of follow-up studies and comparison with the UK PEM study on losartan. The crude rate of cough with losartan treatment was similar to that with calcium channel antagonists, but was significantly less than that with ACE inhibitors.
No novel safety problems were found in this observational cohort study on losartan. The rates of some known ADRs differed significantly between patients treated with losartan and those in the control groups.
1997年和1998年在日本开展了两项处方事件监测试点研究（J-PEM）。在此，我们呈现第二项J-PEM试点研究中报告的不良事件数据，该研究将氯沙坦与血管紧张素转换酶抑制剂及二氢吡啶类钙通道拮抗剂进行了比较。
我们进行了一项设有同期对照的队列研究。
方法/患者组：从医院或社区药房的处方中识别出开具氯沙坦、血管紧张素转换酶抑制剂或钙通道拮抗剂的研究对象。通过邮寄问卷从医生和药剂师处收集事件及其他信息。使用《药物监管活动医学词典》（MedDRA）术语对事件进行编码和分析。计算氯沙坦治疗患者与接受对照药物患者的粗事件发生率并进行比较。当差异具有统计学意义时，对该事件进行多种方式的进一步检查，包括随访研究以及与英国氯沙坦PEM研究的数据进行比较。
向药剂师发送了4344份问卷，回收3591份（83%），向医生发送了3517份问卷，回收1380份（39%）。在医生的数据中，氯沙坦治疗的不良事件发生率在以下七个事件中高于血管紧张素转换酶抑制剂和/或钙通道拮抗剂：头痛、心悸、贫血、失眠、感觉异常、血压升高和哮喘。除血压升高和哮喘这两个事件外，这些大多是氯沙坦已知的药物不良反应（ADR）。在药剂师的数据中，氯沙坦在以下十个事件中的发生率显著高于对照药物：潮热、肝功能异常、水肿、外周肿胀、血压降低、血压升高、鼻炎、接触性皮炎、皮肤干燥和热疹。前五个事件是氯沙坦已知的ADR，但其他五个不是。当两组数据合并时，氯沙坦已知ADR之一的血肌酐磷酸激酶升高这一额外事件的发生率显著高于对照药物。未被记录为氯沙坦ADR的六个事件根据随访研究结果以及与英国氯沙坦PEM研究的比较未被判定为ADR。氯沙坦治疗咳嗽的粗发生率与钙通道拮抗剂相似，但显著低于血管紧张素转换酶抑制剂。
在这项关于氯沙坦的观察性队列研究中未发现新的安全问题。氯沙坦治疗患者与对照组患者中一些已知ADR的发生率存在显著差异。
