Low- vs high-dose ARNI effects on clinical status, exercise performance and cardiac function in real-life HFrEF patients

Abstract

Purpose Only a few studies are available on dose-related effects of sacubitril/valsartan (angiotensin receptor neprilysin inhibition (ARNI)) in real-life patients with heart failure and reduced ejection fraction (HFrEF). We sought to investigate clinical and functional effects in real-life HFrEF patients receiving ARNI at a different cumulative dose. Methods This was an observational study in consecutive outpatients admitted for HFrEF from October 2017 to June 2019. The PARADIGM criteria were needed for enrolment. ARNI was uptitrated according to blood pressure, drug tolerability, renal function and kaliemia. At least 10-month follow-up was required in each patient. Clinical assessment, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, 6-min walk test and strain echocardiography were performed in each patient on a regular basis during the observational period. At the end of the study, patients were divided into two groups based on the median yearly dose of the ARNI medication. Results A total of 90 patients, 64 ± 11 years, 82% males, were enrolled. The cut-off dose was established in 75 mg BID, and the study population was divided into group A (≤ 75 mg), 52 patients (58%), and group B (> 75 mg), 38 patients (42%). The follow-up duration was 12 months (range 11–13). NYHA class, KCCQ score and 6MWT performance ameliorated in both groups, with a quicker time to benefit in group B. The proportion of patients walking > 350 m increased from 21 to 58% in group A ( p < 0.001), and from 29 to 82% in group B ( p < 0.001). A positive effect was also disclosed in the left ventricular remodelling, strain deformation and diastolic function. Conclusion One-year ARNI treatment was effective in our real-life HFrEF patient population, leading to clinical and functional improvement in both study groups, slightly greater and with a shorter time to benefit in group B. Supplementary information The online version contains supplementary material available at 10.1007/s00228-021-03210-0.

Effect of angiotensin receptor neprilysin inhibitor on physical activity in patients with heart failure with reduced ejection fraction, monitored by implantable electronic device home monitoring

“…Another study found that patients who were receiving ARNI doses equal to or exceeding 72/78 mg/day had better functional capacity, as determined by the 6MWT and KCCQ, when compared with patients who received lower doses of ARNI. Importantly, in this study, patients with lower ARNI doses also demonstrated improved functional capacity during the follow-up period 29 . Our study aligns with both of these studies regarding the time frame for improved activity, as we also observed improvement as early as 3–6 months after ARNI initiation.…”

“…Previous research has indicated that ARNI treatment can improve functional capacity in patients with HFrEF. Most of these studies focused mainly on patients who were administered high-dose ARNI 9,28,29 . For instance, a study by Malfatto et al 28 showed an improvement in CPET parameters in patients who were administered with an average dose of 318 mg/day of ARNI after 6 months of treatment.…”

“…Previous studies evaluated functional capacity via CPET or the 6MWT 6,16,17,28–30 . However, these objective tests do not necessarily represent an individual's actual daily physical activity.…”

“…Because of the promising prognostic potential of ARNI, limited by its significant side effects even under guideline-directed doses, studies aiming to evaluate the impact of low-dose ARNI are on the rise. Such studies have shown that a ‘lower than traditionally used’ daily dose of 24/26 mg is both well tolerated and has a similar positive effect compared with higher standard ARNI doses 18–20,29 . The main outcomes evaluated in these studies were cardiovascular death or hospitalizations, cardiac biomarkers, echocardiographic parameters, and health status (as evaluated via the KCCQ) 18–20,29 .…”

Efficacy and safety of sacubitril/valsartan in patients with heart failure with reduced ejection fraction and hypotension

“…Studies have shown that high-dose sacubitril/valsartan can not only improve clinical status, exercise performance, and cardiac function, but also result in a lower mortality or hospitalization rate for HFrEF patients as compared to low-dose therapy [21,22]. As a consequence, our heart failure team developed a rigorous follow-up plan that focused on titrating sacubitril/valsartan to achieve the target dose for HF patients.…”