Effect of heart rate reduction with ivabradine on quality of life in advanced cancer patients

Abstract

Heart failure (HF) and cancer share mutual mechanistic pathways1 and both are characterized by increasing symptoms leading to severe clinical impairments and reduced self-care.2 Heart rate (HR) is elevated in patients with cancer3 and HF,4 where it is associated with outcomes3,4 and quality of life (QoL),5 in particular when blood pressure is low.6 Ivabradine reduces HR4,5 and associates with an improvement of QoL5 and outcomes across the risk spectrum in HF.4 Recently, the EMPATICC trial has shown in a multi-pharma intervention with HF drugs, some changes in QoL in cancer patients.7,8 In EMPATICC, a multi-drug combination therapy was used with ivabradine, sacubitril/valsartan, SGLT2-inhibitors and iron therapy. In this paper we only wanted to look at those patients that received ivabradine exclusively to better understand the effects this medication alone could have on quality of life and clinical parameters.7

We report on our clinical experience of using ivabradine to lower HR in patients with cancer presenting with high HR and complaining about symptoms of shortness of breath. Ethical approval was obtained from the Ethics Committee of the Medical Association of Saarland (Ärztekammer des Saarlandes) for both the Heart Failure and Homburger Cardio-Oncology registries. Between May 2019 and October 2022, we included 12 patients with various types of advanced cancer without the history of HF, a HR ≥ 70 bpm and severe impairment of QoL. All patients underwent chemotherapy or immune-therapy. As there are no comparable, validated tests for quality of life assessment for cardiological patients without HF, QoL was assessed using Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Pre- and post-ivabradine values were compared using the Wilcoxon signed-rank test for paired samples. Results are presented as median (Inter Quartile Ranges, IQR) with an alpha of 5% as well as using the paired Student’s t-test (results are presented as mean (±SEM) with an alpha of 5%).

Resting HR was high (mean 96.4 bpm) and systolic blood pressure (SBP) low (mean 107.5 mmHg). There was an elevation of inflammatory markers such as CRP, without evidence of an acute infection with a normal body temperature (mean 36.7°C). Patients with HF were excluded. For arterial hypertension, 58.3% of patients were on beta-blockers, 50% on ACE inhibitors and 58.3% on diuretics. The ejection fraction was normal or mildly reduced. Ivabradine reduced HR by median change of 25.6 bpm (P < .001) without effecting blood pressure (data not shown). Ivabradine therapy was associated with significant improvement of KCCQ from baseline concerning symptom frequency, total symptom score and symptom stability, while other KCCQ domains showed numerical improvements. There was no heterogeneity between the different components of KCCQ (Figure 1A and B). MLHFQ showed no significant changes (data not shown).