Barriers to the Implementation of Heart Failure Therapy in the Elderly: Let's Accept the Challenge!

This article refers to ‘Impact of age on clinical outcomes and response to serelaxin in patients with acute heart failure: An analysis from the RELAX-AHF-2 trial’ by R.M. Inciardi et al., published in this issue on pages 2431–2439. Heart failure (HF) is estimated to affect around 64.3 million people worldwide in 2017, and its rising prevalence poses a significant public health burden.1 In a meta-analysis of echocardiographic screening studies conducted from 1997 to 2014 in the general population in developed countries the estimated prevalence of HF was about 1% in individuals under 60 and increased to 11.8% in individuals aged ≥60 years.2 Acute HF (AHF) is one of the leading causes of hospital admissions in developed countries.3 Despite HF being a leading cause of morbidity and mortality among elderly patients, they are underrepresented in clinical trials on AHF. In this issue of the Journal, Inciardi and colleagues addressed this important topic and examined the impact of age on clinical outcomes and treatment responses in a sub-analysis of the Relaxin in Acute Heart Failure (RELAX-AHF-2) trial.4 The authors chose this large clinical trial (n = 6600) due to its relatively high mean age of 73.0 ± 11.0 years at the time of recruitment, with more than one third of the enrolled patients being ≥80 years old. To assess the impact of age on outcomes, they divided the cohort into five age categories: <65 (n = 1411), 65–74 (n = 1832), 75–79 (n = 1222), 80–84 (n = 1156), and ≥85 years (n = 924). Their main finding was that cardiovascular mortality and all-cause mortality after 180 days increased with age, remaining significant even after adjusting for clinically relevant confounders. The authors found no clinical benefit on either of the primary endpoints with serelaxin treatment compared to placebo. Additionally, elderly patients experienced significantly longer times to hospital discharge compared to younger patients. As expected, patients in the higher age categories were more likely to be from Western Europe and had a higher prevalence of comorbidities, including hypertension, diabetes mellitus, stroke and other cerebrovascular events, chronic kidney disease (CKD), atrial fibrillation (AF)/atrial flutter, and previous hospitalizations for HF. The use of guideline-directed medical therapy (GDMT), including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists, was significantly less frequent in older age groups. Similarly, cardiac resynchronization therapy was less frequently utilized in elderly patients. In contrast, oral loop diuretics were more frequently prescribed in higher age groups potentially indicating a decompensated disease state. Interestingly, the proportion of patients with HF with reduced ejection fraction (i.e. LVEF ≤40%) decreased in higher age groups suggestive of a predominance of other HF phenotypes in these groups. The higher prevalence of comorbidities such as long-standing hypertension, diabetes, anaemia, CKD, or AF in elderly patients results in a higher proportion of HF with preserved ejection fraction.5 These comorbidities complicate HF treatment and potentially threaten the findings of clinical trials, contributing to their underrepresentation in contemporary research. In recent randomized clinical trials on AHF the median age of the cohorts ranged from 61 (interquartile range [IQR] 51–71) years in PIONEER-HF6 to 71 (IQR 62–78) years in EMPULSE,7 resulting in a notably lower percentage rate of included participants with an age of 80 years or older compared to RELAX-AHF-2. Additionally, physicians' perceived lack of prognostic benefits in elderly patients may further contribute to this. Advanced stages of CKD often hamper the implementation of GDMT. Participants with impaired kidney function are frequently excluded from clinical trials, resulting in a lack of evidence for this patient group. Additionally, there is a discrepancy between used equations to estimate glomerular filtration rate (GFR) in daily clinical practice and those used to estimate GFR (or measure GFR) in approval clinical trials.8 It has been shown, that GFR physiologically declines with increasing age,9 and therefore stopping HF treatment in the elderly due to GFR threshold should be carefully considered. However, also other age-specific factors contribute to lower rates of GDMT in the elderly. Frailty, higher rates of cognitive impairment, depression, and other psychological disorders are significant contributing factors.10, 11 This might result in lower treatment adherence compared to younger HF patients.12 In a sub-analysis of the PARADIGM-HF and ATMOSPHERE trials it has been shown that frailty is highly prevalent amongst patients with HF and is associated with worse outcomes. However, the treatment effect of sacubitril/valsartan in the PARADIGM-HF trial was consistent across both frail and non-frail groups.13 Moreover, a decompensated HF state has been shown to adversely affect cognitive function in elderly patients. However, after recompensation cognitive function could be ameliorated.14 These examples highlight the importance of GDMT implementation even in these vulnerable subgroups. To overcome these barriers, we propose a holistic therapeutic approach that includes the implementation of multidisciplinary care teams, especially within specialized geriatric cardiology units. Comorbidities should be considered but not impede the implementation of GDMT. Treatment goals should be established during the initial hospitalization in collaboration with patients and their families. It is advisable to include a social worker and/or psychologist in the multidisciplinary team to address cognitive impairment, social deprivation, depression, and other psychological disturbances, as well as home care needs, early on. Particular attention should be given to frailty by means of updated scores. A key objective should be to develop concepts that facilitate the transition from hospitalization to the home-based care settings. Recently published data from Japan indicated that outpatient cardiac rehabilitation participation following a hospitalization for AHF is associated with substantial prognostic benefit in a large HF cohort regardless of age or frailty.15 These benefits extended beyond the well-known improvements in health-related quality of life and exercise capacity,16 but also encompassed all-cause mortality and HF-related hospitalization.15 As a result, it is clear why participating in home-based HF rehabilitation programmes can be considered a win-win solution for the elderly.17 Additionally, after discharge, continuous GDMT must be ensured in the outpatient sector. A sub-analysis of the STRONG-HF trial demonstrated that high-intensity care, involving rapid up-titration of GDMT and close follow-up after AHF hospitalization, was safe and led to a significant reduction in all-cause mortality and HF readmissions in the elderly.18 Age discrimination concerning adequate GDMT should be prevented. The use of simple telemonitoring programmes seems to further facilitate the outcome of these patients.19 To mitigate social deprivation and enhance coping with chronic illness, all AHF patients, especially the elderly, should be encouraged to join local HF support groups. While younger patients may prefer online communities, personal interactions can be particularly beneficial for the elderly (Figure 1). Inciardi and colleagues have to be congratulated for their analysis resulting in more evidence for HF treatment in the elderly. For more than 20 years, we are talking about HF treatment and its barriers to the implementation in the elderly.20 Now, it is time to address this in clinical practice. Let's accept the challenge! We thank Armin Schweizer for excellent technical assistance. Conflict of interest: I.E.E. received speaker honoraria from Pharmacosmos, Astellas, Bristol Myers Squibb, AstraZeneca and Novartis. All other authors have nothing to disclose.