Assessing the risk of acute kidney injury associated with a four-drug regimen for heart failure: a ten-year real-world pharmacovigilance analysis based on FAERS events

The four-drug regimen for heart failure with reduced ejection fraction (HFrEF) significantly reduces the risks of hospitalization and mortality. To identify key adverse drug events (ADEs) warranting attention with this regimen, we conducted a real-world pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) events. We collected ADE reports of the four-drug regimen from FAERS that matched this regimen over a 10-year period. Disproportionality analysis and subgroup analysis were performed using four algorithms. Time-to-onset (TTO) analysis was used to assess the temporal risk patterns of ADE occurrence. Lastly, logistic regression was applied to investigate the relationship-value between patient characteristics and ADEs. A total of 1,237 cases with 6,580 ADE reports were collected. Disproportionality analysis identified the most frequent ADEs as hypotension, acute kidney injury (AKI), and hyperkalemia. TTO analysis revealed a median TTO of 39 days for all important medical events, and the median TTO for AKI was 28 days, both fitting an early failure curve. In the comprehensive management of HFrEF with the four-drug regimen, in addition to routine monitoring of ADEs such as hypotension and hyperalemia, early-onset AKI should be a particular focus. Heart failure with reduced ejection fraction (HFrEF) is a condition where the heart doesn’t pump blood as well as it should. There is a recommended treatment plan that includes four specific drugs, which can help reduce the risk of hospitalization and death. However, taking multiple medications can also increase the risk of side effects, known as adverse drug events (ADEs). In this study, we analyzed reports of side effects from people taking this four-drug regimen using data from the FDA Adverse Event Reporting System (FAERS) over the past 10 years (2014–2024). We used different methods to identify common and serious side effects and looked at how quickly these side effects tend to appear after starting treatment. We also examined the role of patient characteristics, like age and body weight, in the occurrence of these side effects. We found that the most frequent side effects were low blood pressure, worsening kidney function (including acute kidney injury), and high potassium levels. On average, serious side effects occurred within 39 days of starting treatment, with kidney problems appearing even sooner (around 28 days). Older patients and males were more likely to experience kidney issues. Based on our findings, we recommend close monitoring of these side effects, especially early in treatment, and adjusting medications as needed to reduce risks. Early changes in drug doses and regular follow-up can help ensure that the treatment is both safe and effective for patients.