Stricker B H, Feenstra J, Ottervanger J P, Porsius A J, Grobbee D E
Drug Safety Unit, Inspectorate for Health Care, Rijswijk, Netherlands.
Neth J Med. 1997 Nov;51(5):163-8. doi: 10.1016/s0300-2977(97)00053-3.
A recent interim analysis of the PRIME II placebo-controlled study showed a significantly higher mortality in the group treated with ibopamine than in the control group. The objective was to study mortality in patients on ibopamine, and to assess risk factors for death.
All 2147 drug-dispensing outlets (DDO) in the Netherlands were asked to provide a printout of the complete medication history of users of ibopamine. A reaction was received from 92% of the DDO. From the 14,024 identified former or current users of ibopamine, a sample of 3148 patients (22%) was enrolled in the follow-up study. All general practitioners (GP) of these patients received an enquiry pertaining to the vital status of their patient, cause of death, primary cause and NYHA classification of heart failure, echo- and electrocardiographic data, serum creatinine, admissions and the effects of ibopamine. Cases were defined as patients who died during the follow-up period which ended on the day of return of the questionnaire or the day of decease (index date). Two random controls were obtained for each case from the non-deceased patients at the index date. The design was a follow-up study with risk factor assessment in a nested case-control design.
Questionnaires were returned regarding almost 70% of the sample. Mortality in this group was 25%. A case-control analysis was performed with the first 104 cases and 208 random controls. Patients with NYHA class IV had a 3-times increased risk of dying. In patients with a serum-creatinine level in the highest quartile the risk of dying was increased threefold. Higher doses of ibopamine seemed to have a protective effect. Significantly more cases than controls used amiodarone. Also, opioids were used more often, which may be related to their use in terminal cardiac failure.
NYHA classification and serum-creatinine levels were independent risk factors for death in patients with heart failure on ibopamine. Although there were increased risk estimates for current use of ibopamine and amiodarone, these did not reach statistical significance. This may be related, however, to the fact that this analysis was restricted to the first 20% of cases.
PRIME II安慰剂对照研究的近期中期分析显示，异波帕胺治疗组的死亡率显著高于对照组。目的是研究使用异波帕胺患者的死亡率，并评估死亡风险因素。
荷兰所有2147个药品配售点（DDO）被要求提供异波帕胺使用者完整用药史的打印件。92%的DDO作出了回应。在14024名确定的异波帕胺既往或当前使用者中，3148名患者（22%）的样本被纳入随访研究。这些患者的所有全科医生（GP）都收到了一份有关其患者生命状态、死亡原因、心力衰竭的主要病因和纽约心脏协会（NYHA）分级、超声心动图和心电图数据、血清肌酐、住院情况以及异波帕胺疗效的询问。病例定义为在随访期内死亡的患者，随访期截至问卷返回日或死亡日（索引日期）。在索引日期，从非死亡患者中为每个病例选取两个随机对照。该设计是一项在巢式病例对照设计中进行风险因素评估的随访研究。
样本中近70%的问卷被返回。该组的死亡率为25%。对前104例病例和208个随机对照进行了病例对照分析。NYHA IV级患者的死亡风险增加了两倍。血清肌酐水平处于最高四分位数的患者死亡风险增加了两倍。较高剂量的异波帕胺似乎具有保护作用。使用胺碘酮的病例明显多于对照。此外，阿片类药物的使用也更频繁，这可能与其在终末期心力衰竭中的使用有关。
NYHA分级和血清肌酐水平是使用异波帕胺的心力衰竭患者死亡的独立风险因素。尽管当前使用异波帕胺和胺碘酮的风险估计有所增加，但未达到统计学显著性。然而，这可能与该分析仅限于前20%的病例这一事实有关。
