Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA)
Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA)
复制标题
乳腺癌辅助治疗期间预防心脏功能障碍 (PRADA)
作者：
S. Heck;A. Mecinaj;A. H. Ree;P. Hoffmann;J. Schulz;MortenW. Fagerland;B. Gravdehaug;H. Røsjø;K. Steine;J. Geisler;G. Gulati;T. Omland
补充数字内容可在文本中找到。背景：蒽环类药物加或不加抗人表皮生长因子受体- 2抗体和放疗的辅助乳腺癌治疗与癌症治疗相关的心功能障碍有关。在PRADA试验（预防乳腺癌辅助治疗期间的心功能障碍）中，血管紧张素受体阻滞剂坎地沙坦的联合治疗减弱了接受乳腺癌治疗的女性左心室射血分数（LVEF）的降低，而β受体阻滞剂美托洛尔则减弱了心脏肌钙蛋白的增加。本研究旨在评估坎地沙坦和美托洛尔或其联合使用对防止心功能下降和心肌损伤的长期影响。方法：在这项2×2因子、随机、安慰剂对照、双盲、单中心试验中，早期乳腺癌患者被分配到坎地沙坦西列地酯、琥珀酸美托洛尔或匹配安慰剂的联合治疗中。目标剂量分别为32毫克和100毫克。辅助治疗后停用研究药物。所有120名有效随机患者均纳入意向治疗分析。主要结局指标是通过心血管磁共振成像评估LVEF从基线到延长随访的变化。次要结局指标包括左心室容积、超声心动图峰值总纵应变和循环心肌肌钙蛋白浓度的变化。结果：随机化后，从基线到延长随访，LVEF略有下降，但组间无显著差异，中位时间为23个月（四分位数范围，21至28个月）（坎地沙坦，1.7% [95% CI， 0.5至2.8]；无坎地沙坦，1.8% [95% CI， 0.6至3.0]；美托洛尔，1.6% [95% CI， 0.4至2.7]；无美托洛尔，1.9% [95% CI， 0.7至3.0]）。与非坎地沙坦组相比，辅助治疗期间坎地沙坦治疗与左心室舒张末期容积显著降低（P=0.021）相关，2年时总体纵向应变下降（P=0.046）减弱。各组心肌肌钙蛋白I和T浓度变化无明显差异。结论：在延长随访期间，蒽环类药物辅助治疗早期乳腺癌与LVEF下降有关。坎地沙坦在辅助治疗期间并不能阻止2年LVEF的降低，但与左室舒张末期容积的适度降低和整体纵向应变的保留有关。这些结果表明，对于大多数没有先前存在心血管疾病的早期乳腺癌患者，可能不需要广泛施用心脏保护方法。注册：网址：https://www.clinicaltrials.gov；唯一标识符：NCT01434134。
Supplemental Digital Content is available in the text. Background: Adjuvant breast cancer therapy containing anthracyclines with or without anti–human epidermal growth factor receptor–2 antibodies and radiotherapy is associated with cancer treatment–related cardiac dysfunction. In the PRADA trial (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy), concomitant treatment with the angiotensin receptor blocker candesartan attenuated the reduction in left ventricular ejection fraction (LVEF) in women receiving treatment for breast cancer, whereas the β-blocker metoprolol attenuated the increase in cardiac troponins. This study aimed to assess the long-term effects of candesartan and metoprolol or their combination to prevent a reduction in cardiac function and myocardial injury. Methods: In this 2×2 factorial, randomized, placebo-controlled, double-blind, single-center trial, patients with early breast cancer were assigned to concomitant treatment with candesartan cilexetil, metoprolol succinate, or matching placebos. Target doses were 32 and 100 mg, respectively. Study drugs were discontinued after adjuvant therapy. All 120 validly randomized patients were included in the intention-to-treat analysis. The primary outcome measure was change in LVEF assessed by cardiovascular magnetic resonance imaging from baseline to extended follow-up. Secondary outcome measures included changes in left ventricular volumes, echocardiographic peak global longitudinal strain, and circulating cardiac troponin concentrations. Results: A small decline in LVEF but no significant between-group differences were observed from baseline to extended follow-up, at a median of 23 months (interquartile range, 21 to 28 months) after randomization (candesartan, 1.7% [95% CI, 0.5 to 2.8]; no candesartan, 1.8% [95% CI, 0.6 to 3.0]; metoprolol, 1.6% [95% CI, 0.4 to 2.7]; no metoprolol, 1.9% [95% CI, 0.7 to 3.0]). Candesartan treatment during adjuvant therapy was associated with a significant reduction in left ventricular end-diastolic volume compared with the noncandesartan group (P=0.021) and attenuated decline in global longitudinal strain (P=0.046) at 2 years. No between-group differences in change in cardiac troponin I and T concentrations were observed. Conclusions: Anthracycline-containing adjuvant therapy for early breast cancer was associated with a decline in LVEF during extended follow-up. Candesartan during adjuvant therapy did not prevent reduction in LVEF at 2 years, but was associated with modest reduction in left ventricular end-diastolic volume and preserved global longitudinal strain. These results suggest that a broadly administered cardioprotective approach may not be required in most patients with early breast cancer without preexisting cardiovascular disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01434134.
DOI：
10.1016/j.jcmg.2018.01.015
发表时间：
2018-08
期刊：
JACC. Cardiovascular imaging
影响因子：
--
作者：
Zhang KW;Finkelman BS;Gulati G;Narayan HK;Upshaw J;Narayan V;Plappert T;Englefield V;Smith AM;Zhang C;Hundley WG;Ky B
通讯作者：
Ky B
影响因子：
24
作者：
Guglin, Maya;Krischer, Jeffrey;Munster, Pamela N.
通讯作者：
Munster, Pamela N.
DOI：
10.1016/j.amjcard.2017.02.008
发表时间：
2017-05-15
期刊：
The American journal of cardiology
影响因子：
--
作者：
Meléndez GC;Sukpraphrute B;D'Agostino RB Jr;Jordan JH;Klepin HD;Ellis L;Lamar Z;Vasu S;Lesser G;Burke GL;Weaver KE;Ntim WO;Hundley WG
通讯作者：
Hundley WG