Warfarin-associated bleeding events and concomitant use of potentially interacting medicines reported to the Norwegian spontaneous reporting system

In Norway, antithrombotic drugs have been the drugs most often reported to the Norwegian spontaneous reporting system with fatal outcome for a number of years. Antithrombotic drugs, such as warfarin and platelet inhibitors, are effective in thrombosis prevention, but are also frequently implicated in drug-induced bleeding. Drug-induced bleeding is among the most serious adverse drug reactions and contributes to a substantial morbidity, mortality, health cost and cost to society. Despite the substantial knowledge about risk factors of druginduced bleeding, there is still a gap in knowledge with regard to risk factors and outcome among patient subgroups. Little is known about use of interacting drugs at the time of bleeding, or how physicians assess drug interactions in cases from the spontaneous reporting system. The list of drug interactions and drugs associated with bleeding is long and increasing, but for some commonly used older drugs controversy still exists regarding bleeding risk. In this study we used different pharmacoepidemiological study designs to explore the association between the use of antithrombotic drugs and drug-induced bleeding. First, we aimed to explore reporting patterns of bleeding adverse drug reactions reported to the Norwegian spontaneous reporting system, the extent of potential drug interactions, and concordance in assessment between reporters and evaluators. Next, we used a hospitalbased trauma registry to investigate whether use of pre-injury antithrombotic drugs affected mortality after head trauma. Then, in a study with case-control design, we explored whether the use of antithrombotic drugs affected platelet activity among patients admitted to hospital with gastrointestinal bleeding. Last, we investigated the association between the use of corticosteroids and risk of gastrointestinal bleeding in a systematic review and meta-analysis