Concomitant use of drugs known to cause interactions with oral antiplatelets—polypharmacy in acute coronary syndrome outpatients in Finland

PURPOSE: Use of oral antiplatelets (OAPs) is essential for preventing thrombotic events in patients with acute coronary syndrome (ACS). Effects of clopidogrel, prasugrel, and ticagrelor may be enhanced due to pharmacodynamic interactions, but as CYP substrates, they are prone to pharmacokinetic interactions too. The aim was to study polypharmacy in ACS patients following hospital discharge. METHODS: This observational drug utilization study linked patient-level data from nationwide registers. The study population consisted of adult ACS patients discharged from Finnish hospitals in 2009-2013. Logistic regression was used to model the probability of drug-drug interactions with odd ratios for predefined predictors such as age, gender, and ACS type. RESULTS: In the cohort of 54,416 ACS patients, 91% of those treated with OAP received clopidogrel. Of clopidogrel-treated patients, 12% purchased warfarin at least once while on clopidogrel treatment. Old age, male sex, ST-elevation myocardial infarction as index event, and a history of previous ACS events were associated with an increased risk of warfarin-OAP interaction (p < 0.001 for all). Ibuprofen, and serotonergic drugs tramadol, citalopram, and escitalopram were the next most common drugs causing pharmacodynamic interactions. In general, concomitant use of drugs known to cause pharmacokinetic interactions was rare, but both esomeprazole and omeprazole were prescribed in more than 6% of clopidogrel-treated patients. CONCLUSIONS: Warfarin and ibuprofen were the most commonly used concomitant medications causing pharmacodynamic interactions and potentially increasing the risk of bleeding in OAP-treated patients. Esomeprazole and omeprazole were used in clopidogrel-treated patients although there are alternatives available for gastric protection.