Effect of prophylactic betablocker or ACE inhibitor on cardiac dysfunction & heart failure during anthracycline chemotherapy ± trastuzumab.

Administration of anthracycline chemotherapy ± trastuzumab is associated with cardiac dysfunction. We sought to identify whether prophylactic administration of angiotensin converting enzyme (ACE) inhibitor or beta-blocker attenuates subsequent left ventricular dysfunction and heart failure. Electronic databases were searched for studies examining the effect of beta-blockers or ACE inhibitors on left ventricular ejection fraction (LVEF) and heart failure in patients receiving anthracycline chemotherapy ± trastuzumab. The end-point was change in LVEF or development of heart failure. Eight studies (1048 patients) were identified. There was no difference in the change in LVEF (weighted mean difference (MWD) - 4.74 (95% confidence interval (CI): -12.6 to 3.1), p = 0.24) or risk of new heart failure diagnosis (Odds ratio (OR) 0.24 (95% CI: 0.03-1.73), p = 0.16) between patients receiving ACE inhibitor or control. Betablocker use was associated with a significant smaller drop in LVEF compared to control (MWD -3.28 (95% CI: -6.1 to -0.51), p = 0.02) but not in patients who received anthracycline chemotherapy alone (MWD - 3.05 (95% CI -7.22 to 1.12), p = 0.15). There was a significant reduction in new heart failure diagnosis in those receiving beta-blocker compared to those not (OR 0.33 (95% CI: 0.14-0.80), p = 0.01). Prophylactic ACE inhibitor does not attenuate development of LV dysfunction or heart failure in patients receiving anthracycline chemotherapy ± trastuzumab. Beta-blocker attenuated reduction in LVEF and new heart failure diagnosis. However, the effect in patients only receiving anthracycline is less certain. Studies examining the effect on mortality are required.

Gujral DM ，Lloyd G ，Bhattacharyya S 《-》

Left ventricular dysfunction in patients receiving cardiotoxic cancer therapies are clinicians responding optimally?

The purpose of this study was to examine treatment practices for cancer therapy-associated decreased left ventricular ejection fraction (LVEF) detected on echocardiography and whether management was consistent with American College of Cardiology/American Heart Association guidelines. Patients treated with anthracyclines or trastuzumab are at risk of cardiotoxicity. Decreased LVEF represents a Class I indication for drug intervention according to American College of Cardiology/American Heart Association guidelines. Patients receiving anthracycline or trastuzumab at Stanford University from October 2005 to October 2007 and who had undergone echocardiography before and after receiving an anthracycline or trastuzumab were identified. Chart review examined chemotherapy regimens, cardiac risk factors, imaging results, concomitant medications, and cardiology consultations. Eighty-eight patients received therapy with an anthracycline or trastuzumab and had a pre-treatment and follow-up echocardiogram. Ninety-two percent were treated with anthracyclines, 17% with trastuzumab after an anthracycline, and 8% with trastuzumab without previous treatment with anthracycline. Mean baseline LVEF was 60%, with 14% having a baseline <55%. Forty percent had decreased LVEF (<55%) after anthracycline and/or trastuzumab treatment. Of these patients, 40% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 51% beta-blocker therapy, and 54% cardiology consultation. Of patients with asymptomatic decreased LVEF, 31% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 35% beta-blocker therapy, and 42% cardiology consultation. Of those with symptomatic decreased LVEF, 67% received angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, 100% beta-blocker therapy, and 89% cardiology consultation. Many cancer survivors are not receiving treatment consistent with heart failure guidelines. There is substantial opportunity for collaboration between oncologists and cardiologists to improve the care of oncology patients receiving cardiotoxic therapy.

Yoon GJ ，Telli ML ，Kao DP ，Matsuda KY ，Carlson RW ，Witteles RM ... -  《-》

Cardioprotective effect of renin-angiotensin inhibitors and β-blockers in trastuzumab-related cardiotoxicity.

Ohtani K ，Ide T ，Hiasa KI ，Sakamoto I ，Yamashita N ，Kubo M ，Tsutsui H ... -  《-》

A systematic review and meta-analysis of beta-blockers and renin-angiotensin system inhibitors for preventing left ventricular dysfunction due to anthracyclines or trastuzumab in patients with breast cancer.

Trastuzumab and anthracyclines, often used in the treatment of breast cancer, may impair myocardial function, and reduce left ventricular ejection fraction (LVEF), potentially causing heart failure. Randomized controlled trials (RCTs) have evaluated the effects of beta-blockers (BBs), angiotensin receptor blockers (ARBs), and angiotensin-converting enzyme inhibitors (ACEI) on trastuzumab- and anthracycline-associated cardiotoxicity. We report a meta-analysis of these RCTs in patients with breast cancer. The primary analysis was on the effect of BBs and ACEI/ARBs on LVEF in patients treated with either trastuzumab or anthracyclines. A secondary analysis was done investigating the effect of BBs or ACEI/ARBs on LVEF in trastuzumab and anthracycline treatments. Only RCTs were included using the search term 'ARBs, ACEIs, BBs, anthracyclines, trastuzumab, and breast cancer' in PubMed, Embase, and CENTRAL up to 31 March 2021. A meta-analysis was conducted to estimate the mean difference (MD) in LVEF between intervention and placebo groups at follow-up. A total of nine RCTs (n = 1362) were included in the analysis. All patients were women. BBs and ACEI/ARBs were shown to attenuate the decline in LVEF during trastuzumab and anthracycline treatments [MD: 2.4; 95% confidence interval (CI): 0.3-4.2 and MD: 1.5; 95% CI: -0.6 to 3.7]. Compared with placebo, LVEF was significantly higher in patients assigned to BB or ACEI/ARB on trastuzumab (MD: 2.3; 95% CI: 0.0-4.6) but not on anthracyclines (MD: 1.9; 95% CI: -0.5 to 4.2). Both BB and ACEI/ARB therapies were associated with the preservation of LVEF during trastuzumab and anthracycline-containing regimens as compared with placebo, suggesting both to be beneficial.

Lewinter C ，Nielsen TH ，Edfors LR ，Linde C ，Bland JM ，LeWinter M ，Cleland JGF ，Køber L ，Braunschweig F ，Mansson-Broberg A ... -  《-》

Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: a systematic review and meta-analysis.

Cardiotoxicity is a well-recognised complication of chemotherapy with anthracycline and/or trastuzumab, and its prevention remains an important challenge in cancer survivorship. Several successful preventative strategies have been identified in animal trials. We sought to assemble the clinical evidence that prophylactic pharmacological interventions could prevent left ventricular (LV) dysfunction and heart failure in patients undergoing chemotherapy. We undertook a systemic review of the evidence from randomised trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal ejection fraction and no past history of heart failure. The primary outcome was development of heart failure (HF), a drop in ejection fraction (EF) or both. A random-effects model was used to combine relative risks (RR) and 95% confidence intervals (CIs), and a meta-regression was undertaken to assess the impact of potential covariates. Data were collated from 14 published articles (n=2015 paediatric and adult patients) comprising 12 randomised controlled trials and two observational studies. The most studied chemotherapeutic agents were anthracyclines, and prophylactic agents included dexrazoxane, statins, beta-blocker and angiotensin antagonists. There were 304 cardiac events in the control arm compared to 83 in the prophylaxis arm (RR=0.31 [95% CI: 0.25-0.39], p<0.00001). Cardiac events were reduced with dexrazoxane (RR=0.35 [95% CI 0.27-0.45], p<0.00001), beta-blockade (RR=0.31 [95% CI 0.16-0.63], p=0.001), statin (RR=0.31 [95% CI 0.13-0.77], p=0.01) and angiotensin antagonists (RR=0.11 [95% CI 0.04-0.29], p<0.0001). Prophylactic treatment with dexrazoxane, beta-blocker, statin or angiotensin antagonists appear to have similar efficacy for reducing cardiotoxicity.

Kalam K ，Marwick TH 《-》