Systemic fluconazole use linked to bleeding risk in atrial fibrillation patients: Study

Denmark: In a new study conducted by Anders Holt and team it was found that in patients with atrial fibrillation on apixaban, rivaroxaban, or dabigatran, a link was discovered between increased bleeding risk and the use of systemic fluconazole. The findings of this study were published in The American Journal of Medicine.

Despite clinical importance and multiple findings suggesting links, bleeding safety in connection to systemic fluconazole and topical azoles among patients with atrial fibrillation treated with apixaban, rivaroxaban, or dabigatran is understudied. In atrial fibrillation patients on apixaban, rivaroxaban, or dabigatran, this study looked at the risk of bleeding after either systemic antifungal treatment with fluconazole or topical antifungal treatment with any azole agent.

This study was based on administrative health registers from across Denmark that this group had previously used. Researchers identified individuals with atrial fibrillation who were started on apixaban, rivaroxaban, or dabigatran between 2012 and 2018 using Danish records. They then used a case-crossover design with 30-day exposure windows to look for links between bleeding occurrences and systemic fluconazole or topical azole medication and provided odds ratios (OR). 

The key findings of this study are as follow:

1. In total 32,340 (36%), 32,409 (36%), and 24,940 (28%), respectively, were included, patients who were started on apixaban, rivaroxaban, and dabigatran.

2. Patients on apixaban were older than those taking rivaroxaban or dabigatran. Apixaban users had a higher risk of bleeding after taking systemic fluconazole: odds ratio (OR) 3.5. Users of rivaroxaban and dabigatran had no elevated risk, with ORs of 0.9 and 1.7, respectively.

3. There was no connection between bleeding risk and topical azole exposure among apixaban, rivaroxaban, and dabigatran users, with ORs of 0.8, 1.3, and 1.2, respectively.

In conclusion, a substantial correlation between an enhanced bleeding risk and the use of systemic fluconazole was discovered among individuals on apixaban alone in a statewide cohort of patients with atrial fibrillation on NOACs. Co-exposure to topical azoles did not result in a significantly higher risk of bleeding.

Reference: 

Holt A, Strange JE, Rasmussen PV, Blanche P, Nouhravesh N, Jensen MH, Schjerning AM, Schou M, Torp-Pedersen C, Gislason GH, Hansen ML, McGettigan P, Lamberts M. Bleeding Risk Following Systemic Fluconazole or Topical Azoles in Patients with Atrial Fibrillation on Apixaban, Rivaroxaban, or Dabigatran. Am J Med. 2021 Nov 30:S0002-9343(21)00793-2. doi:10.1016/j.amjmed.2021.11.008. Epub ahead of print. PMID: 34861201.