[Calcium inhibiting drugs and the risk of gastrointestinal hemorrhage. A pharmaco-epidemiologic case-non-case study].

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.