Applying the ‘Touch-and-Go’ Concept to Mineralocorticoid Receptor Antagonists: A Paradigm Shift in Routine Heart Failure Management

This article refers to ‘Discontinuation and reinitiation of mineralocorticoid receptor antagonists in patients with heart failure and reduced ejection fraction’ by L. Landucci et al., published in this issue on pages xxx. Mineralocorticoid receptor antagonists (MRAs) are pivotal in the management of heart failure (HF) with reduced ejection fraction (HFrEF), offering robust reductions in mortality and hospitalizations. Despite their clear benefits, real-world adherence to MRAs remains suboptimal, primarily due to concerns about worsening renal function (WRF) and hyperkalaemia. In this context, the study published in this issue by Landucci et al.1 on the Swedish HF registry data sheds light on the patterns of discontinuation and reinitiation of MRAs, providing a deeper understanding of the practical barriers to maintaining therapy. The study reveals that 71% of patients initiated on MRAs remained on therapy after 1 year, with discontinuation being more frequent during the initial months. Importantly, nearly half of those who discontinued restarted therapy within a year, with reinitiation occurring predominantly within the first 3 months after discontinuation. Predictors of discontinuation included advanced age, lower renal function, hyperkalaemia, and the absence of follow-up in specialty care. These findings echo broader registry data, highlighting the challenges posed by renal dysfunction and electrolyte abnormalities. Moreover, the study draws attention to the higher discontinuation rates associated with spironolactone compared to eplerenone (53% vs. 34%),1 a finding corroborated by Danish nationwide data.2 Worsening renal function and hyperkalaemia remain the primary reasons for discontinuation of MRAs, yet the clinical approach to these challenges often errs on the side of excessive caution. As emphasized by several recommendations,3 including the one endorsed by the French HF Working Group specifically related to the management of guideline-directed medical therapy (GDMT) in the context of WRF,4 the renal effects of MRAs (and other renin–angiotensin–aldosterone system inhibitors) are functional rather than toxic. A moderate rise in creatinine or potassium should not lead to abrupt cessation, particularly given the life-saving benefits of these therapies. A practical approach to these barriers, as emphasized in the consensus statement from the French HF Working Group,4 includes: (i) systematic evaluation of reversible factors such as dehydration, infection, or nephrotoxic drug use; (ii) tailored management strategies for specific scenarios, including hyperkalaemia and WRF, with the aim of continuing therapy whenever possible; and (iii) close biological monitoring after therapeutic adjustments. In addition, there is growing consensus on recalibrating our tolerance for mild renal dysfunction (creatinine increase <50% or estimated glomerular filtration rate [eGFR] remaining >25 ml/min/1.73 m2) and electrolyte abnormalities (K+ <5.5 or 6 mmol/L), thereby reducing unnecessary discontinuations.4 Recently, strong evidence further supported this approach. Matsumoto et al.5 showed in a pooled individual patient data analysis from RALES and EMPHASIS-HF that those patients who experienced a deterioration of eGFR after randomization to <30 ml/min/1.73 m2 (295 out of 4355 patients included) had worse HF outcome. The risk reduction in the primary outcome with MRA therapy was similar in those who experienced a decrease in eGFR to <30 ml/min/1.73 m2 (hazard ratio [HR] 0.65; 95% confidence interval [CI] 0.43–0.99) compared with those who did not (HR 0.63; 95% CI 0.56–0.71). Therefore, the absolute risk reduction in these patients was large by maintaining the MRA treatment.5 This further reinforce the need for a voluntaristic approach to MRA in patients with WRF. Importantly, the concomitant use of sodium–glucose cotransporter 2 (SGLT2) inhibitors and MRAs reduces the risk of hyperkalaemia compared to the use of MRAs alone.6 As both SGLT2 inhibitors and MRA are indicated for the treatment of HFrEF, these agents should be used concomitantly, unless contraindicated. Potassium binders, such as patiromer, may be considered in patients with past hyperkalaemia or with a high risk of developing hyperkalaemia.7 Some potassium binders, such as sodium zirconium cyclosilicate, may be less adapted to a use in HF patients as they increase sodium load and may worsen HF outcomes.8 Despite these strategies, some patients will not tolerate MRAs and even despite an adequate management of hyperkalaemia, certain levels of WRF may correctly worry clinicians and need a thorough investigation and early re-assessment. A concept which we herein call ‘touch-and-go’. The concept of ‘touch-and-go’ management reflects the intermittent discontinuation and reinitiation of MRAs, a practice that occurs sporadically in clinical settings but remains underutilized and insufficiently explored in HF management (Figure 1). While not yet widely adopted, this approach has shown promise in other medical fields. For example, in oncology, intermittent androgen deprivation therapy has been successfully employed in prostate cancer, striking a balance between treatment efficacy and quality of life, with outcomes comparable to continuous therapy.9 Similarly, in HIV management, a trial explored a 4-days-on, 3-days-off antiretroviral regimen, achieving sustained viral suppression while reducing drug exposure.10 In asthma, combining inhaled corticosteroids and formoterol in a single inhaler for both daily maintenance and as-needed symptom relief has improved symptom control, enhanced medication adherence, and allowed flexible dose adjustments to reduce the risk of severe episodes while simplifying treatment.11 These examples suggest a similar potential in HF management, where intermittent therapy may support better adherence and outcome. Historically, this approach has been underemphasized in HF guidelines. However, as Landucci et al.1 demonstrate, even temporary interruptions need not signify the end of MRA therapy (though in a minority of patients). By focusing on early reinitiation and addressing the root causes of discontinuation, clinicians can ensure more consistent use of these life-saving agents. Similarly, reintroducing MRAs at a very low dose (e.g. 25 mg every other day) can support continued therapy, aligning with the paradigm of ‘maintaining at least a minimal dose of all GDMT’. This approach is particularly relevant in the context of renal deterioration and low blood pressure, where preserving some degree of therapeutic benefit is preferable to discontinuation.12 Of note, this approach requires robust follow-up systems, including specialized HF nurse-assisted HF clinics and multidisciplinary care models.13, 14 These strategies not only support adherence but also provide the infrastructure for safe monitoring and timely reintroduction of therapy. In this ‘touch-and-go’ framework, the comparative findings on eplerenone and spironolactone add a valuable perspective. Eplerenone's lower discontinuation rates, combined with its rapid pharmacokinetics—allowing quick onset and clearance—make it especially suited for this dynamic approach to MRA management.2 While both agents achieve similar clinical outcomes, eplerenone's reduced risk of treatment interruption may enhance adherence and support better long-term results. This positions eplerenone as a preferable choice, particularly when spironolactone has been discontinued or in patients with a higher risk of worsening renal function or hyperkalaemia. Mineralocorticoid receptor antagonists are cornerstone therapies for HFrEF, but their benefits can only be realized through sustained use. The findings by Landucci et al.1 and corroborating evidence emphasize the need for a paradigm shift in managing the barriers to MRA continuation. By adopting a more tolerant stance on WRF and hyperkalaemia, embracing the ‘touch-and-go’ concept, with a focus on prioritizing eplerenone when appropriate, we can optimize the use of MRAs and improve outcomes for patients with HFrEF. Conflict of interest: N.G. reports honoraria from AstraZeneca, Bayer, Boehringer, Lilly, Echosens, NP medical, Novartis, Novo Nordisk, Roche Diagnostics. All other authors have nothing to disclose.