Heart failure from cancer therapy: can we prevent it?

Abstract

Aims Conventional cytotoxic chemotherapy is still among the most effective treatment options for many types of cancer. However, cardiotoxicity, notably the decrease in left ventricular function under these regimens, can impair prognosis. Thus, prevention and treatment of cardiotoxicity are crucial. The present meta‐analysis aims to assess the efficacy of beta‐blockers or angiotensin‐converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) for prevention of cardiotoxicity. Methods and results We systematically searched Pubmed, Cochrane, EMBASE, and Web of Science databases for randomized controlled trials published until February 2019. The analysis included randomized studies that reported on left ventricular ejection fraction (LVEF) after 6 months of chemotherapy in cancer patients who received beta‐blockers or ACE inhibitors/ARBs for prevention of cardiotoxicity compared with controls. Studies on combination cardioprotective therapies were excluded from the analysis. The primary endpoint was prevention of a decrease in LVEF as defined by the individual study and as assessed by either transthoracic echocardiography or magnetic resonance imaging. We here show that patients under anthracycline‐based chemotherapy have a moderate yet significant benefit in LVEF from beta‐blockers or ACEs/ARBs. The beta‐blocker analysis included 769 cancer patients, and the ACE inhibitors/ARBs analysis included a total of 581 cancer patients. The mean LVEF difference between the beta‐blocker group and the control group was 2.57% (95% confidence interval 0.63–4.51, P = 0.009). The mean difference for ACE inhibitors/ARBs was 4.71% (95% confidence interval 0.38–9.03, P = 0.03). However, the beneficial effects throughout the studies were variable as documented by significant heterogeneity between the studies. Conclusions Systematic evidence is needed to solidly found recommendations for cardioprotective prevention during chemotherapy. Likewise, trials on other neurohumoral drugs (spironolactone) and lipid‐lowering approaches are required to improve protection for cardio‐oncology patients.

The mRNA expression of Il6 and Pdcd1 are predictive and protective factors for doxorubicin‑induced cardiotoxicity

“…Pharmacological strategies for preventing DICT have also been proposed in many studies; β-blockers, ACE inhibitors, ARBs and statins can reduce DICT in animals and in humans ( 1 , 10 , 13 ). It is noteworthy that dexrazoxane, which reduces oxidative stress (by iron chelation) and inhibits topoisomerase IIβ, protects the heart from anthracycline-induced toxicity ( 21 , 59 , 60 ).…”

“…Several strategies for reducing the risk of heart failure in anthracycline-treated patients have been proposed, including pharmacological therapy to prevent cardiotoxicity ( 10 ). Although some antioxidants, such as vitamin E and probucol, have been observed to provide cardioprotective action in DOX-treated animal models ( 2 , 11 ), there is (to date) no direct evidence supporting clinically efficacy ( 12 ).…”

“…Although some antioxidants, such as vitamin E and probucol, have been observed to provide cardioprotective action in DOX-treated animal models ( 2 , 11 ), there is (to date) no direct evidence supporting clinically efficacy ( 12 ). Alternatively, it has been demonstrated (in both animals and humans) that standard drugs for heart failure, such as β-blockers and angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), are effective in attenuating DOX-induced cardiac damage ( 2 , 10 , 13 ). In fact, pharmacological therapy with these drugs is generally accepted as a preventive strategy against cardiac dysfunction in anthracycline-treated patients ( 10 ).…”

“…Alternatively, it has been demonstrated (in both animals and humans) that standard drugs for heart failure, such as β-blockers and angiotensin-converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs), are effective in attenuating DOX-induced cardiac damage ( 2 , 10 , 13 ). In fact, pharmacological therapy with these drugs is generally accepted as a preventive strategy against cardiac dysfunction in anthracycline-treated patients ( 10 ). It should be noted, however, that the response rate to the pharmacological therapy progressively decreases with increasing time delay between the end of chemotherapy to the onset of cardiac dysfunction (i.e., with delayed start of the pharmacological therapy) ( 13 , 14 ).…”

Heart failure in the last year: progress and perspective

“…58,59,88 On the other hand, cancer patients frequently develop HF, due to cardiotoxicity. 60,[89][90][91][92][93] In breast cancer patients, increased levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and impaired global longitudinal strain (GLS) were found in 34% and 23% of the patients, respectively. GLS and left ventricular ejection fraction (LVEF) declined with increasing cumulative anthracycline dose.…”