sacubitril and Neoplasms

Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. However, there are very limited data on the efficacy of sacubitril/valsartan in the prevention and treatment of cardiotoxicity. This systematic review aimed to evaluate the potential benefit of sacubitril/valsartan in patients with CTRCD.. The databases included MEDLINE, Embase, LILACS, Scopus and Cochrane Central up to January 20, 2022. All pre-clinical and clinical studies including observational studies (cohorts, case-control, cross-sectional and case reports) that used sacubitril/valsartan for prevention or treatment of CTRCD. The primary effectiveness endpoints was CTRCD, defined as a clinically significant change in left ventricular ejection fraction (LVEF) at the end of the follow-up.. And after applying the eligibility criteria, 12 articles (9 in humans and 3 preclinical studies) were included in this systematic review. The 3 preclinical studies demonstrated beneficial effects in preventing, attenuating and/or delaying the onset of myocardial damage at the cellular level, ventricular dysfunction and remodeling. Regardind human studies, most of them were composed of case reports. The largest study consisted of a retrospective multicentric cohort with 64 patients.. All clinical studies have demonstrated that used Sac/Val in human showed a significant increase in LVEF, and when reported, a reduction in left ventricular volume and NT-proBNP (or BNP). Randomized clinical trials are needed to confirm this hypothesis.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cross-Sectional Studies; Drug Combinations; Heart Failure; Humans; Neoplasms; Retrospective Studies; Stroke Volume; Tetrazoles; Valsartan; Ventricular Function, Left

Advances in cancer therapy have resulted in more cancer therapy-related cardiac dysfunction (CTRCD), which is the main cause of death in older female survivors of breast cancer. Traditionally, guideline-recommended medications for heart failure, such as beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), are commonly used to prevent or attenuate CTRCD. However, sometimes their effectiveness is not satisfactory. Recently, the drug combination of sacubitril plus valsartan has been proven to be more beneficial for heart failure with reduced ejection fraction in the long term compared with an ACEI/ARB alone. However, there is a lack of evidence of the efficacy and safety of this drug combination in CTRCD. We report a case of worsening CTRCD, despite treatment with traditional medications, in which the patient improved after changing perindopril to sacubitril/valsartan. The patient's heart function greatly improved after changing this ACEI to sacubitril/valsartan. Changing an ACEI/ARB to sacubitril/valsartan in patients with worsening chemotherapy-induced heart failure is appropriate. Further studies with a high level of evidence are required to assess the efficacy and safety of sacubitril/valsartan for CTRCD.

Topics: Aged; Aminobutyrates; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Biphenyl Compounds; Drug Combinations; Female; Heart Failure; Humans; Neoplasms; Stroke Volume; Tetrazoles; Treatment Outcome; Valsartan

Immune checkpoint inhibitors (ICIs) have become a new hope for many patients with advanced cancer by blocking tumour immune evasion. However, with the widespread use of ICIs, immune-related adverse events (irAEs) have also been discovered and reported increasingly. Immune-related myocarditis, the most dangerous one of irAEs, still has high mortality in the context of the current treatment. We report the case of a 60-year-old female with fulminant myocarditis induced by ICIs, which caused her to experience frequent ventricular arrhythmias such as ventricular fibrillation and heart failure. She was successfully treated with current mainstream therapies for immune-related myocarditis and additional treatment of sacubitril-valsartan and dapagliflozin. The intriguing observation that the patient condition recovered relatively rapidly in this case shows a possible treatment inspiration, which may be helpful for treating ICIs-associated myocarditis and improving cancer patients' clinical prognosis.

Topics: Aminobutyrates; Biphenyl Compounds; Female; Humans; Immune Checkpoint Inhibitors; Middle Aged; Myocarditis; Neoplasms

Cancer patients are at an increased risk of cardiovascular events. Both old-generation cytostatics/cytotoxics and new-generation "targeted" drugs can in fact damage cardiomyocytes, endothelial cells of veins and arteries, specialized cells of the conduction system, pericardium, and valves. A new discipline, cardio-oncology, has therefore developed with the aim of protecting cancer patients from cardiovascular events, while also providing them with the best possible oncologic treatment. Anthracyclines have long been known to elicit cardiotoxicity that, depending on treatment- or patient-related factors, may progress with a variable velocity toward cardiomyopathy and systolic heart failure. However, early compromise of diastolic function may precede systolic dysfunction, and a progression of early diastolic dysfunction to diastolic rather than systolic heart failure has been documented in long-term cancer survivors. This chapter first describes general notions about hypertension in the cancer patient and then moves on reviewing the pathophysiology and clinical trajectories of diastolic dysfunction, and the molecular mechanisms of anthracycline-induced diastolic dysfunction. Diastolic dysfunction can in fact be caused and/or aggravated by hypertension. Pharmacologic foundations and therapeutic opportunities to prevent or treat diastolic dysfunction before it progresses toward heart failure are also reviewed, with a special emphasis on the mechanisms of action of drugs that raised hopes to treat diastolic dysfunction in the general population (sacubitril/valsartan, guanylyl cyclase activators, phosphodiesterase inhibitors, ranolazine, inhibitors of type-2 sodium-glucose-inked transporter). Cardio-oncologists will be confronted with the risk:benefit ratio of using these drugs in the cancer patient.

Topics: Aminobutyrates; Anthracyclines; Antineoplastic Agents; Biphenyl Compounds; Cardiomyopathies; Endothelial Cells; Heart Failure, Systolic; Humans; Hypertension; Neoplasms

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiotoxicity; Drug Combinations; Heart Failure; Humans; Neoplasms; Stroke Volume; Tetrazoles; Valsartan

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biphenyl Compounds; Cardiotoxicity; Drug Combinations; Heart Failure; Humans; Neoplasms; Stroke Volume; Tetrazoles; Valsartan