Sex differences in the effectiveness of mhealth in post-discharge heart failure care: a subanalysis of the hermes multicenter randomised controlled trial

Background Heart failure (HF) remains a major global health burden, particularly during the post-discharge ‘vulnerable phase’. Mobile health (mHealth) interventions integrating telemonitoring and structured teleintervention have shown promise in improving outcomes, yet their sex-specific effectiveness remains underexplored. Given known biological and gender-related disparities in HF presentation and care, this subanalysis of the HERMeS trial aimed to assess whether mHealth benefits differ between women and men. Methods HERMeS was a 24-week, multicentre, randomised, controlled, open-label trial with blinded endpoint adjudication, enrolling patients recently discharged (≤30 days) after HF decompensation. Participants were randomised 1:1 to mHealth (daily telemonitoring and videoconference-based teleintervention) or usual care (UC). The primary endpoint was a composite of cardiovascular (CV) death or worsening HF, analysed using Cox models. This pre-specified subanalysis evaluated treatment effect modification by sex, with interaction terms tested for statistical significance. Results Of 506 patients, 207 (41%) were women. Women were older, more likely to have HF with preserved ejection fraction (HFpEF), and exhibited greater social and functional vulnerability. The mHealth intervention significantly reduced the primary endpoint in both sexes, with a more pronounced effect in women (event rate: 13.5% vs. 49.0%, HR 0.21, 95% CI 0.11–0.37; p<0.001) than in men (19.4% vs. 35.5%, HR 0.49, 95% CI 0.31–0.78; p=0.002). The interaction between sex and treatment was significant (p=0.026), as shown in Table 1. Similar trends were observed for secondary outcomes, including worsening HF (HR 0.18 in women vs. 0.42 in men; p-interaction=0.038) and urgent HF visits (HR 0.12 in women vs. 0.59 in men; p-interaction=0.015), also detailed in Table 1. Recurrent event analysis of the primary outcome confirmed these findings, showing a lower cumulative incidence of events in the mHealth group compared to usual care, with a steeper divergence in women (rate ratio [RR] 0.28, 95% CI 0.13–0.63; p=0.018) than in men (RR 0.68, 95% CI 0.45–1.02; p=0.067), as illustrated in Figure 1. Women receiving mHealth also had more ambulatory contacts and earlier diuretic adjustments, with significantly fewer intravenous/subcutaneous diuretic episodes (5 vs. 34; p<0.001), suggesting more effective outpatient management. Conclusions mHealth significantly improved outcomes in both sexes post-HF discharge, with greater relative benefit in women, who had higher baseline vulnerability. These findings underscore the importance of sex-specific evaluation in digital health and suggest mHealth may help mitigate disparities in HF care. Further research is warranted to elucidate underlying mechanisms and optimise personalised mHealth strategies.