Sacubitril/valsartan is well tolerated in patients with longstanding heart failure and history of cancer and improves ventricular function: real-world data

Abstract

Background Sacubitril/valsartan has been shown to significantly reduce cardiovascular mortality and hospitalizations due to heart failure in patients with reduced ejection fraction (HFrEF) when compared to enalapril. Data about sacubitril/valsartan in patients with a history of cancer are scarce, as these patients were excluded from the pivotal trial, PARADIGM-HF. The aim of the current study was to assess tolerability of sacubitril/valsartan in patients with a history of cancer. Methods We identified 225 patients at our heart failure out-patient unit who fulfilled the indication criteria to receive sacubitril/valsartan. Out of these, 9.3% (n = 21) had a history of histologically confirmed cancer. Oncologic surgery was performed in 16 (76.2%) patients, 11 (52.4%) patients received previous antineoplastic therapy and 9 patients (42.9%) radiation. Results Sacubitril/valsartan was withdrawn in 3 of 21 patients (14.3%) because of dizziness (n = 2) or pruritus (n = 1). After a median follow-up of 12 months (range 1–34 months), NYHA functional class improved significantly from NYHA 3 to NYHA 2 (mean -0.6, p = 0.006) and left ventricular ejection fraction as assessed by echocardiography increased significantly from 26.8 ± 5.4% to 39.2 ± 10% (mean + 12%, CI 95% [8.4–16.4], p = 0.0004). NT-proBNP was significantly reduced (baseline median 2774 pg/ml, range 1441 – 12,982 vs follow-up 1266 pg/ml, range 199–6324, p = 0.009). There was no significant change in creatinine levels (1.18 ± 0.4 vs 1.22 ± 0.4 mg/dl; mean + 0.005 mg/dl, CI 95% [-0.21- 0.12], p = 0.566). Conclusions In our pilot study we show that sacubitril/valsartan is generally well tolerated in patients with HFrEF and history of cancer. Importantly, even patients with long-standing cardiotoxicity induced heart failure can be treated and up-titrated with sacubitril/valsartan to usual target dosages, leading to improvement in LV function and biomarkers. Larger studies are needed to confirm these findings in cancer patients with cardiotoxicity.

Platinum drugs-related safety profile: The latest five-year analysis from FDA adverse event reporting system data

“…The well-known Dexrazoxane, A CardioProtective Agent Specific for Anthracy cline Chemotherapy, in addition to Continuous Cardiac monitoring, baseline and regular Electrocardiographic and echocardiographic studies, Carvedilol or Nebivolol, ACE inhibitor, ARB (Sacubitril/Valsartan) or Spironolactone, Statins, Dexrazoxane ( 37 ) and Butyric acid can be used to treat or prevent cardiotoxicity caused by chemotherapy drugs ( 38 , 39 ).…”

Molecular mechanisms of sacubitril/valsartan in cardiac remodeling

“…It also improved LVEF in rats administered doxorubicin (Boutagy et al, 2020). Significant favorable effects of sacubitril/valsartan on cardiac function were also noted in patients with cancer therapy-related cardiac dysfunction (Sheppard and Anwar 2019;Gregorietti et al, 2020;Martín-Garcia et al, 2020;Frey et al, 2021;Xi et al, 2022).…”

Cancer treatment-related cardiotoxicity: a focus on sacubitril/valsartan

“…Studies which evaluated sacubitril/valsartan in the context of CTRCD were reviewed in Table 3 [78][79][80][81][82][83][84][85][86][87][88] . A retrospective case study described two anthracycline-related cardiomyopathy survivors with HFrEF who were treated with sacubitril/valsartan with success after poor responses to conventional evidence-based drug treatment [78] .…”