Sex and marital status modify the effect of remote patient management on mortality risk in patients hospitalized for acute systolic heart failure: Insights from the E-INH study
Authors: Kerwagen F , Sehner S , Albert J , Morbach C , Gueder G , Sahiti F , Cejka V , Scholz N , Frantz S , Ertl G , Angermann C E , Stoerk S 
Published: November 2023

Abstract

Background
The multitude of sex-specific effects and the prognostic relevance of marital status in patients with heart failure (HF) are well established. While the remote patient management (RPM) approach deployed in the Extended Interdisciplinary Network Heart Failure (E-INH) trial did not reduce the primary endpoint of time to all-cause death or rehospitalization (composite), questions remain regarding whether the effect of RPM might vary across subgroups of sex and marital status.

Purpose
To investigate the impact of sex and marital status on the effect of RPM in the E-INH trial.

Methods
This is a post-hoc analysis of data from the multicenter E-INH study in Germany. The 18-month intervention consisted of a non-invasive, telephone-based, nurse-led RPM program and was compared to care as usual (UC), in patients hospitalized for acute HF (AHF) and with reduced left ventricular ejection fraction &lt;40% after discharge from the hospital. For the purpose of this study, we used flexible parametric survival models (Royston-Parmar models) to assess the prognostic impact of sex, marital status, and RPM on the following exploratory endpoints: all-cause death, time to first HF hospitalization, and the composite of death or HF hospitalization (time to first event) after 18 and 60 months.

Results
1008 of 1022 randomized patients provided information on marital status at baseline. Their mean age was 68±13 years, 285 (28%) were women, and 633 (63%) were married. As shown in the table, there were several differences in baseline characteristics between the four subgroups of sex (women vs men) and marital status (married vs unmarried). After adjustment for established risk factors in HF, we found a significant three-way interaction between sex, marital status, and RPM for all-cause mortality for both time periods, i.e. after 18 months (p=0.015) and 60 months (p=0.004). The triad of being married, female, and receiving RPM was associated with the best outcome, while the corresponding counterpart, i.e. being unmarried, male, and receiving UC, with the least favorable prognosis (Figure, left panels). Moreover, the protective effect of RPM on survival varied between different subgroups of sex and marital status: RPM reduced the risk of death by 68% after 18 months (HR 0.32, 95% CI 0.10-0.98) and by 56% after 60 months (HR 0.44, 95% CI 0.22-0.88) for married women, and there was a similar trend for unmarried men after 60 months (HR 0.66, 95% CI 0.43-1.02). Contrarily, RPM reduced the time to first HF hospitalization irrespective of marital status and sex.

Conclusion
In this post-hoc analysis of the E-INH trial we demonstrate a relevant interaction between sex, marital status, and the effect of RPM. Although external validation of our findings is still needed, there appears to be a need to tailor RPM approaches to the individual requirements including the social and sex-specific background of patients following AHF to yield optimal treatment results.Baseline characteristics by subgroupsOutcome analysis by subgroups