Austin David, Maier Rebecca H, Akhter Nasima, Sayari Mohammad, Ogundimu Emmanuel, Maddox Jamie M, Vahabi Sharareh, Humphreys Alison C, Graham Janine, Oxenham Helen, Haney Sophie, Cresti Nicola, Verrill Mark, Osborne Wendy, Wright Kathryn L, Goranova Rebecca, Bailey James R, Kalakonda Nagesh, Macheta Mac, Kilner Mari F, Young Moya E, Morley Nick J, Neelakantan Pratap, Gilbert Georgia, Thomas Byju K, Graham Richard J, Fujisawa Takeshi, Mills Nicholas L, Hildreth Victoria, Prichard Jonathan, Kasim Adetayo S, Hancock Helen C, Plummer Chris
Academic Cardiovascular Unit, James Cook University Hospital, South Tees Hospitals NHS Foundation Trust, Middlesbrough, United Kingdom.
Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom.
JACC CardioOncol. 2024 Aug 27;6(5):684-696. doi: 10.1016/j.jaccao.2024.07.010. eCollection 2024 Oct.
Cardiotoxicity is a concern for cancer survivors undergoing anthracycline chemotherapy. Enalapril has been explored for its potential to mitigate cardiotoxicity in cancer patients. The dose-dependent cardiotoxicity effects of anthracyclines can be detected early through the biomarker cardiac troponin.
The PROACT (Preventing Cardiac Damage in Patients Treated for Breast Cancer and Lymphoma) clinical trial assessed the effectiveness of enalapril in preventing cardiotoxicity, manifesting as myocardial injury and cardiac function impairment, in patients undergoing high-dose anthracycline-based chemotherapy for breast cancer or non-Hodgkin lymphoma.
This prospective, multicenter, open-label, randomized controlled trial employed a superiority design with observer-blinded endpoints. A total of 111 participants, scheduled for 6 cycles of chemotherapy with a planned dose of ≥300 mg/m doxorubicin equivalents, were randomized to receive either enalapril (titrated up to 20 mg daily) or standard care without enalapril.
Myocardial injury, indicated by cardiac troponin T (≥14 ng/L), during and 1 month after chemotherapy, was observed in 42 (77.8%) of 54 patients in the enalapril group vs 45 (83.3%) of 54 patients in the standard care group (OR: 0.65; 95% CI: 0.23-1.78). Injury detected by cardiac troponin I (>26.2 ng/L) occurred in 25 (47.2%) of 53 patients on enalapril compared with 24 (45.3%) of 53 in standard care (OR: 1.10; 95% CI: 0.50-2.38). A relative decline of more than 15% from baseline in left ventricular global longitudinal strain was observed in 10 (21.3%) of 47 patients on enalapril and 9 (21.9%) of 41 in standard care (OR: 0.95; 95% CI: 0.33-2.74). An absolute decline of >10% to <50% in left ventricular ejection fraction was seen in 2 (4.1%) of 49 patients on enalapril vs none in patients in standard care.
Adding enalapril to standard care during chemotherapy did not prevent cardiotoxicity in patients receiving high-dose anthracycline-based chemotherapy. (PROACT: Can we prevent Chemotherapy-related Heart Damage in Patients With Breast Cancer and Lymphoma?; NCT03265574).
心脏毒性是接受蒽环类化疗的癌症幸存者所关注的问题。已对依那普利减轻癌症患者心脏毒性的潜力进行了探索。蒽环类药物的剂量依赖性心脏毒性作用可通过生物标志物心肌肌钙蛋白早期检测到。
PROACT（预防乳腺癌和淋巴瘤患者心脏损伤）临床试验评估了依那普利在预防接受高剂量蒽环类药物化疗的乳腺癌或非霍奇金淋巴瘤患者心脏毒性（表现为心肌损伤和心功能损害）方面的有效性。
这项前瞻性、多中心、开放标签、随机对照试验采用了具有观察者盲法终点的优效性设计。共有111名计划接受6个周期化疗且计划剂量≥300mg/m多柔比星等效剂量的参与者被随机分配接受依那普利（滴定至每日20mg）或不使用依那普利的标准治疗。
依那普利组54名患者中有42名（77.8%）在化疗期间及化疗后1个月出现心肌损伤（心肌肌钙蛋白T≥14ng/L），而标准治疗组54名患者中有45名（83.3%）出现该情况（比值比：0.65；95%置信区间：0.23 - 1.78）。接受依那普利治疗的53名患者中有25名（47.2%）检测到心肌肌钙蛋白I损伤（>26.ng/L），而标准治疗组53名患者中有24名（45.3%）出现该情况（比值比：1.10；95%置信区间：0.50 - 2.38）。接受依那普利治疗的47名患者中有10名（21.3%）左心室整体纵向应变较基线相对下降超过15%，标准治疗组41名患者中有9名（21.9%）出现该情况（比值比：0.95；95%置信区间：0.33 - 2.74）。接受依那普利治疗的49名患者中有2名（4.1%）左心室射血分数绝对下降>10%至<50%，而标准治疗组患者中无此情况。
在化疗期间将依那普利添加到标准治疗中并不能预防接受高剂量蒽环类药物化疗患者的心脏毒性。（PROACT：我们能否预防乳腺癌和淋巴瘤患者化疗相关心脏损伤？；NCT03265574）
