Highlights
- Finerenone significantly increases the incidence of post-baseline systolic blood pressure (SBP) <100 mm Hg and investigator-reported hypotension in patients with HFmrEF and HFpEF.
- The primary clinical benefits of finerenone (reduction in HF events and CV death) remain robust in patients who do not experience hypotension, though the effect may attenuate following a hypotensive event.
- Key predictors for hypotension include advanced age, lower baseline SBP, higher NT-proBNP levels, and a history of smoking.
- Clinicians are advised to monitor blood pressure closely rather than automatically discontinuing finerenone upon the observation of low SBP.
Introduction: The Role of Mineralocorticoid Receptor Antagonists in Heart Failure
Heart failure with mildly reduced ejection fraction (HFmrEF) and preserved ejection fraction (HFpEF) represents a significant and growing portion of the global heart failure population. Historically, therapeutic options for these patients were limited compared to those with reduced ejection fraction (HFrEF). However, the landscape has shifted with the introduction of SGLT2 inhibitors and, more recently, nonsteroidal mineralocorticoid receptor antagonists (MRAs).
Finerenone, a potent and selective nonsteroidal MRA, differs from traditional steroidal MRAs like spironolactone or eplerenone. It has demonstrated a more balanced distribution between the heart and kidneys and a lower affinity for other steroid receptors, theoretically reducing the risk of side effects such as hyperkalemia and gynecomastia. The FINEARTS-HF trial recently established finerenone’s efficacy in reducing the composite of total heart failure events and cardiovascular death in patients with LVEF ≥40%. However, like all therapies impacting the renin-angiotensin-aldosterone system (RAAS), the risk of hypotension remains a clinical concern. This prespecified analysis delves into the nuances of finerenone-related hypotension, its predictors, and its impact on long-term clinical outcomes.
Study Design: Probing the FINEARTS-HF Data
The FINEARTS-HF trial was a randomized, double-blind, placebo-controlled, multicenter study. It enrolled symptomatic patients with chronic heart failure and a left ventricular ejection fraction (LVEF) of 40% or higher. Participants were randomized to receive either finerenone (uptitrated to 20 mg or 40 mg daily based on eGFR) or a matching placebo.
In this specific sub-analysis, researchers focused on 5,815 participants with available blood pressure data. The objectives were threefold: to identify predictors of systolic blood pressure (SBP) <100 mm Hg, to evaluate investigator-reported hypotension, and to assess how these blood pressure changes influenced the efficacy of the randomized treatment. The primary endpoint remained the composite of total heart failure events (first and recurrent) and cardiovascular death. Researchers utilized Cox proportional hazards models and time-updated models to analyze the associations between hypotension and clinical outcomes.
Key Findings: Quantifying the Hypotensive Risk
Incidence and Odds
The analysis revealed a clear increase in hypotensive episodes within the finerenone group. Post-baseline SBP <100 mm Hg was observed in 899 patients. Specifically, 538 patients in the finerenone arm experienced this drop compared to 361 in the placebo arm. This resulted in an odds ratio (OR) of 1.60 (95% CI: 1.38-1.85). Investigator-reported hypotension followed a similar trend, occurring in 225 patients on finerenone versus 139 on placebo (OR: 1.67; 95% CI: 1.34-2.08).
Predictors of Low Blood Pressure
Identifying which patients are most at risk is critical for clinical management. The study found several baseline characteristics that were independently associated with an increased risk of SBP <100 mm Hg:
- Baseline SBP: Lower initial SBP was the strongest predictor.
- Age: Older patients were more susceptible to blood pressure drops.
- NT-proBNP: Higher levels of this cardiac biomarker correlated with a higher risk of hypotension, likely reflecting more advanced disease or cardiac fragility.
- Smoking History: A history of smoking was associated with increased risk.
- Diabetes Status: Interestingly, the absence of diabetes was associated with a higher risk of SBP <100 mm Hg in this cohort.
Impact on Clinical Efficacy
A pivotal question for clinicians is whether the occurrence of hypotension negates the benefits of finerenone. The data showed that the treatment-related risk reduction for the primary endpoint was most pronounced in patients who did not experience SBP <100 mm Hg (Rate Ratio [RR]: 0.78; 95% CI: 0.67-0.90). In the period following a recorded SBP <100 mm Hg, the benefit appeared to attenuate (RR: 0.99; 95% CI: 0.70-1.39). However, it is essential to note that the formal statistical interaction test was not significant (P-interaction = 0.33), suggesting that the overall benefit of finerenone likely persists across these subgroups, though perhaps with varying degrees of magnitude.
Expert Commentary: Navigating the Hypotension Challenge
The findings from this FINEARTS-HF analysis highlight a classic pharmacological trade-off. While finerenone is effective in reducing major cardiovascular events, its physiological impact on fluid balance and vascular tone can lead to hypotension, particularly in vulnerable populations. The lack of a significant statistical interaction between hypotension and treatment effect is reassuring; it suggests that hypotension is a manageable side effect rather than a reason to avoid the drug entirely.
From a mechanistic standpoint, the nonsteroidal nature of finerenone allows for potent MR antagonism without some of the off-target effects of earlier generations. However, the blood pressure-lowering effect is a known class effect of MRAs. In the context of HFpEF, where patients are often older and have multiple comorbidities, hypotension can lead to falls, syncope, or acute kidney injury. Therefore, the “Goldilocks” approach to blood pressure management—achieving a target low enough to reduce strain but high enough to maintain organ perfusion—is paramount.
Experts suggest that when a patient on finerenone experiences a drop in SBP below 100 mm Hg, clinicians should first evaluate the patient’s entire medication regimen. It may be more appropriate to adjust the dosages of concurrent diuretics or other antihypertensives before discontinuing a life-prolonging therapy like an MRA. Clinical monitoring should be intensified during the initiation and titration phases, especially for those identified as high-risk in this study.
Conclusion and Summary
The FINEARTS-HF trial has solidified finerenone’s place in the management of HFmrEF and HFpEF. This secondary analysis provides critical safety data, showing that while finerenone increases the risk of hypotension, this risk is predictable based on baseline patient characteristics. The primary takeaway for the clinical community is that hypotension should be viewed as a signal for closer monitoring and potential regimen adjustment rather than an absolute contraindication or a trigger for automatic discontinuation. By identifying at-risk patients—such as the elderly and those with low baseline SBP—physicians can better tailor their monitoring strategies to maximize the therapeutic benefits of finerenone while minimizing adverse events.
Funding and Registration
The FINEARTS-HF trial was funded by Bayer AG. ClinicalTrials.gov Identifier: NCT04435626.
References
Foà A, Vaduganathan M, Claggett BL, et al. Finerenone-Related Risk of Hypotension in Heart Failure With Mildly Reduced or Preserved Ejection Fraction. JACC Heart Fail. 2025 Dec 6:102779. doi: 10.1016/j.jchf.2025.102779. Epub ahead of print. PMID: 41364043.