ACE抑制剂与β受体阻滞剂或许可预防化疗导致的心脏毒性

1化疗中造成的持久性心脏毒性对患者来说是一种灾难：癌症患者从威胁生命的癌症疾病中康复之后，却被癌症治疗所导致的另一疾病-心力衰竭而压垮。
目前，在临床治疗中如果出现心脏问题就要停止化疗，但这也意味着心脏已经受损。最好的方案是在治疗初期就采取预防心脏受损的措施，一项前导性研究的作者这样说道，该研究发表于2013年4月10日发行的《美国心脏病学会学报》电子版。
Xavier Bosch博士（西班牙巴塞罗钠Hospital Clinic胸腔研究所）与其同事报道说，在癌症患者进行大剂量化疗时给予心血管治疗药物可能会防止造成患者持久性的心脏损害。在两组进行大剂量化疗的癌症患者中，联合血管紧张素转化酶（ACE）抑制剂和β受体阻滞剂治疗的试验组似乎可以预防左心室射血分数（LVEF）降低。
Bosch与其同事评论说，这些结果可能“有重要的意义，因为全球每年有数百万的癌症患者接受化疗，有大量患者在与这种疾病抗争，”。但他们还补充说，这种预防方案“需要通过将来更大规模的研究来证实。”
Otto Smiseth博士（挪威奥斯陆大学医院）与其同事在一份相关评论中表示大规模多中心临床试验是必要的，并指出当前的研究存在几项局限，他们同时也哀叹这一领域的研究进展过于缓慢。
他们评论说，“令人吃惊的是，在有心脏风险的癌症患者身上检验这种治疗方案已经有15年的时间了，这些药物明显地降低了死亡率，”。他们还说，在心脏病学和肿瘤学之间需要一种更好、更快的知识转化，最近发明的专业名词心脏肿瘤学就是在正确方向上迈出的第一步。
与化疗相关的拓展阅读：

• ASO：p53与食管癌化疗缓解率相关
• 新型化疗药物保育抗癌双管齐下
• Radiother Oncol：N1小细胞食管癌治疗首选放化疗
• JAMA：度洛西汀可减轻化疗所致的疼痛
• SGO:无铂化疗不能提高宫颈癌患者生存率
• SGO：腹膜内灌注化疗可提高卵巢癌患者生存率
更多信息请点击：有关化疗更多资讯

ACE inhibitor, beta blocker may thwart cardiotoxicity from chemotherapy: Pilot study
Barcelona, Spain - Lasting cardiac damage from chemotherapy is a tragedy: cancer patients are cured of one life-threatening disease, only to succumb to another—heart failure—as a result of the treatment.
Current clinical practice is to stop chemotherapy if cardiac problems develop, but this means that the heart has already been damaged. A better strategy would be to prevent the damage in the first place, say the authors of a pilot study published online April 10, 2013 in the Journal of the American College of Cardiology [1].
Dr Xavier Bosch (Thorax Institute, Hospital Clinic, Barcelona, Spain) and colleagues report that cardiovascular drugs administered to cancer patients while they undergo intensive chemotherapy may protect their hearts from lasting damage. The treatment, a combination of the ACE inhibitor enalapril and the beta-blocker carvedilol, appeared to prevent the reduction in left ventricular ejection fraction (LVEF) seen in control patients, after both groups had undergone intensive chemotherapy for their cancer.
These results could "have important implications, since each year millions of patients with cancer are treated with chemotherapy worldwide and are surviving the disease in great numbers," Bosch and colleagues comment. However, they add that this prevention strategy "should be confirmed in larger future studies."
In an accompanying editorial [2], Dr Otto Smiseth (Oslo University Hospital, Norway) and colleagues say that large multicenter trials are needed, pointing out several limitations to the current study, and they also lament on the slow progress in this field.
"It is striking that it has taken 15 years" to go from general heart failure, where these drugs have markedly reduced mortality, "to testing this strategy in cancer patients at risk from heart failure," they comment. There needs to be a better and faster translation of knowledge between cardiology and oncology, and the recently created specialty of cardioncology is a step in the right direction, they add.
OVERCOME Trial
The study, known as Prevention of Left Ventricular Dysfunction With Enalapril and Carvedilol in Patients Submitted to Intensive Chemotherapy for the Treatment of Malignant Hemopathies (OVERCOME), was conducted in 90 patients with various hematological malignancies. Thirty-six patients had recently been diagnosed with acute leukemia; the remaining 54 patients (22 with multiple myeloma, 23 with Hodgkin's disease, nine with non-Hodgkin's lymphoma) were undergoing autologous hematopoietic stem-cell transplantation.
All patients received intensive high-dose chemotherapy: the regimens were not specified in the paper, but the authors mention that the patients with acute leukemia received anthracyclines, which are notoriously cardiotoxic, while the other patients did not.
Half of the patients (n=45) were randomly assigned to receive enalapril and carvedilol, while the other half served as controls. LVEF was measured before and after chemotherapy by both cardiac magnetic resonance (CMR) and echocardiography.
The authors report that after six months, LVEF had not changed in the patients who had received enalapril plus carvedilol, but it had decreased significantly in the controls, resulting in a -3.1% absolute difference by echocardiography (p=0.035) and a -3.4% absolute difference by CMR (p=0.09).
However, the editorialists point out that a follow-up CMR was performed in only 59 of the 90 patients, and the difference between the treated and control patients was "only marginally significant." But follow-up echocardiography was carried out in 79 of 90 patients, and this showed a significant difference, they add.
The apparent protective effect of enalapril plus carvedilol was more pronounced in the subgroup of 36 patients with acute leukemia, who received the more cardiotoxic chemotherapy regimens, the authors note. In this subgroup, the absolute difference in LVEF between treated patients and controls was -6.38%.
However, there was little difference in the LVEF among the remaining 54 patients with other hematologic malignancies (absolute difference -1%).
Effects on mortality?
The results suggest that patients treated with enalapril and carvedilol fared better overall than controls and that they suffered from less cardiac damage. The treated patients had a lower incidence of the combined end point of death and heart failure (6.7% vs 22% in controls, p=0.036) and also had a lower incidence of the combined end point of death, heart failure, or final LVEF <45% (6.7 vs 24.4%, p=0.02).
However, the authors note that two-thirds of the deaths were related to infectious complications in the context of postchemotherapy neutropenia, and so "it is difficult to elucidate whether enalapril and carvedilol could have influenced mortality."
In their editorial, Smiseth and colleagues say the design of the trial "leaves many questions that need an answer." The trial was not blinded, did not compare the combination of ACE inhibitor and beta-blocker with single agents, and the means of detecting ventricular function "was to some degree inadequate."
Future studies should include assessment of LV function by strain imaging and should also assess diastolic function and correct hypertension in order to reduce the deleterious effects of chemotherapy on cardiac function, they suggest.

{nextpage}