OBJECTIVES:

The effects of anti-hypertensive drugs could be potentiated by the drug-drug interaction (DDI) with direct-acting antiviral agents (DAAs) through the inhibition of P-glycoprotein and/or cytochrome P450, especially in hepatitis C virus (HCV) infected patients with polypharmacy. However, the real-world clinical significance of hypotension has not been well-evaluated and needs to be characterized.

METHODS:

A retrospective cohort study was conducted by utilizing a multicenter electronic medical records database from May 2017 to February 2022 in Taiwan. HCV-infected patients receiving at least one examination for genotyping and completing DAA (sofosbuvir/velpatasvir, SOF/VEL; glecaprevir/ pibrentasvir, GLE/PIB) course were included. Potential DDIs were screened using University of Liverpool database. We further analyzed the impact of DDIs on the change of blood pressure (BP). Logistic regression was applied to estimate the association between the occurrence of DDI and hypotension, defined as systolic BP measured < 90 mmHg or diagnosed with an associated International Classification of Diseases code.

RESULTS:

Overall, 6799 patients (SOF/VEL: 49.9% and GLE/PIB: 50.1%) were enrolled with a mean age of 62.0 years, and most of the patients were genotype 2 HCV (42.4%). A significant decrease in BP was observed in patients with DDI compared with patients without DDI (-8.7 vs. -11.3 mmHg, p < 0.0001). 64 patients had at least one hypotensive event. The risk of hypotension was higher in GLE/PIB group with DDI after controlling Charlson comorbidity index (CCI), especially in patients with CCI scores of 1 to 2 (odds ratio: 4.5, 95% confidence interval: 1.5 – 13.4). Additionally, we found that hypotension was positively associated with DDI among patients with anti-hypertensive agent use (0.4% vs. 1.4%, p=0.0493).

CONCLUSIONS:

Present findings confirm that patients with DDI caused by DAA and anti-hypertensive agents were at risk of hypotension. Health care providers should be vigilant in identifying DAA-related DDIs, BP monitoring and considering medication adjustment if needed.