Thrombocheck: a drug-drug interactions guide for cardiologists prescribing antithrombotic therapy

Abstract Background Antithrombotic therapies (AT; including oral anticoagulants OAC and antiplatelet agents AA) are highly prescribed in cardiology wards. Drug-drug interactions (DDI) can compromise their efficacy or safety due to under or overexposure. While an OAC DDI table was published in recent European guidelines 1, clear data about DDI for AA is lacking. We aimed to elaborate a comprehensive and updated DDI guide to assist cardiologists in safely prescribing AT to patients in our hospital. Purpose To review the available literature on all relevant DDI between AT and co-medications known to cause pharmacokinetic (PK) DDI which may be prescribed on a cardiology ward. Methods First, a clinical pharmacist and a physician independently analysed the literature on DDI for 8 AT: 5 OAC (rivaroxaban, apixaban, edoxaban, dabigatran and acenocoumarol) and 3 AA (clopidogrel, ticagrelor and prasugrel). Aspirin was excluded as it is not known for PK DDI. The main references consulted were national and international summary of product characteristics, 2021 and 2024 European guidelines 1, 2, several DDI databases (i.e. UpTodate® or Micromedex®) and Pubmed in case of conflicting data. The findings were then compared and stratified according to the level of DDI for each case. Finally, 6 additional experts (one haematologist, three cardiologists, one intensive care specialist and one pharmacist) validated this guide. When uncertainty remained regarding the clinical relevance of the DDI, the more cautious option was adopted. Results We identified 39 drugs that are frequently prescribed in cardiology wards and that may cause DDI, as summarised in Figure 1 and 2. The 165 DDI found in this review were classified in five levels: major (red, 12% of the DDI), moderate (orange, 11%) or weak (yellow, 44%) increase in AT exposure or major (dark blue, 12%) and moderate/weak (light blue, 19%) decrease in AT exposure. For AA, the impact of a single interacting drug can vary significantly depending on the specific AA used. Moderate and major DDI involve not only prescribed medications but also over the counter (OTC) drugs. In a few cases, the AT itself significantly influenced the co-medication exposure (Figure 2, pink, 2% of the DDI). The colour codes were determined solely based on the DDI severity; other factors affecting AT exposure, such as age, renal function or weight, were not considered in this analysis. Therefore, a careful case-by-case assessment is needed before switching from one AT to another. In general, switching AT is recommended for red and dark blue DDI and encouraged for orange and light blue DDI. Additionally, if two yellow DDI are present for the same patient, a therapy review is advised as well. Conclusion Antithrombotic therapies are susceptible to numerous DDI. This simple yet important tool can help cardiologists minimize significant DDI when prescribing new AT, guiding them toward safer et more effective treatment options.