Desboeuf K, Lapeyre-Mestre M, Montastruc J L
Service de pharmacologie clinique, Centre Midi-Pyrénées de pharmacovigilance, de pharmaco-épidémiologie et d'informations sur le médicament, hôpitaux de Toulouse, faculté de médecine.
Arch Mal Coeur Vaiss. 1999 Aug;92(8):1095-9.
Calcium antagonists were found to be associated with an increased risk of gastrointestinal haemorrhage (GIH) in hypertensive patients over 67 years old (Pahor et al. Lancet 1996; 347 : 1061). This unexpected result led us to investigate this question using the French pharmacovigilance system database. We use the case/non case methodology (Moore et al. Br J Pharmacol 1997; 44 : 513) where cases and non cases were both identified from the spontaneous adverse drug reaction (ADR) reporting database. Cases were reports of the reaction of interest (i.e. GIH as recorded in the database). Non cases were all reports of reactions other than being studied. Exposure was considered as the presence in a report of the drug of interest (calcium antagonists), whether or not it was suspected of causing the reaction. We calculated Odds ratios (OR) as the ratio of the Odds of the association of reports of GIH with calcium antagonists in cases and in non cases. Calcium antagonists included in the present study were dihydropyridines, diltiazem, verapamil and bepridil. Salicylates and non steroidal antiinflammatory drugs were used as positive controls. Among the 112,792 ADRs recorded in the database between January 1985 and December 1996, 864 (0.8%) were GIH. There was no association between GIH and the exposure to calcium antagonists whatever the class of the drugs (OR = 1.2, 95% CI: [0.9; 1.6]. A subgroup analysis among the GIH reported in patients over 65 years old (470 GIH from 37,462 ADRs) also failed to find any association (OR = 0.7, 95% CI: [0.5-1.0%]). The present results failed to confirm the hypothesis of an association between GIH and use of calcium antagonists.
钙拮抗剂被发现与67岁以上高血压患者胃肠道出血（GIH）风险增加有关（帕霍尔等人，《柳叶刀》1996年；347:1061）。这一意外结果促使我们利用法国药物警戒系统数据库来研究这个问题。我们采用病例/非病例方法（摩尔等人，《英国药理学杂志》1997年；44:513），病例和非病例均从自发药物不良反应（ADR）报告数据库中识别。病例是所关注反应的报告（即数据库中记录的GIH）。非病例是除所研究反应之外的所有反应报告。暴露被视为报告中存在所关注药物（钙拮抗剂），无论其是否被怀疑导致该反应。我们计算比值比（OR），即病例组和非病例组中GIH报告与钙拮抗剂关联的比值。本研究中包括的钙拮抗剂有二氢吡啶类、地尔硫䓬、维拉帕米和苄普地尔。水杨酸盐和非甾体抗炎药用作阳性对照。在1985年1月至1996年12月数据库记录的112,792例ADR中，864例（0.8%）为GIH。无论药物类别如何，GIH与钙拮抗剂暴露之间均无关联（OR = 1.2，95%可信区间：[0.9；1.6]）。对65岁以上患者报告的GIH进行的亚组分析（37,462例ADR中的470例GIH）也未发现任何关联（OR = 0.7，95%可信区间：[0.5 - 1.0%]）。目前的结果未能证实GIH与钙拮抗剂使用之间存在关联的假设。
