Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol.
Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 × 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol.
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DOI：
10.1093/eurheartj/ehw022
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发表时间：
2016-06-01
影响因子：
39.3
通讯作者：
Omland T
中科院分区：
文献类型：
--
作者：
Gulati G;Heck SL;Ree AH;Hoffmann P;Schulz-Menger J;Fagerland MW;Gravdehaug B;von Knobelsdorff-Brenkenhoff F;Bratland Å;Storås TH;Hagve TA;Røsjø H;Steine K;Geisler J;Omland T
早期乳腺癌的当代辅助治疗与生存率的提高有关，但代价是心脏毒性和心功能障碍的风险增加。我们检验了血管紧张素受体阻滞剂坎地沙坦或β受体阻滞剂美托洛尔的联合治疗将减轻左心室射血分数（LVEF）的下降，这与辅助治疗、含蒽环类药物、曲妥珠单抗和放疗相关。在一项2 × 2因子、随机、安慰剂对照、双盲试验中，我们将130名患有早期乳腺癌且无严重合并症的成年女性分配到血管紧张素受体阻滞剂坎地沙坦西列地酯、β受体阻滞剂琥珀酸美托洛尔或与辅助抗癌治疗平行的安慰剂组。主要指标是通过心脏磁共振成像测量LVEF的变化。先验地，5个百分点的变化被认为具有临床重要性。坎地沙坦与美托洛尔治疗间无交互作用（P = 0.530）。意向治疗分析中，安慰剂组LVEF总体下降2.6 （95% CI 1.5, 3.8）个百分点，坎地沙坦组下降0.8 （95% CI−0.4,1.9）个百分点（组间差异p值：0.026）。没有观察到美托洛尔对LVEF整体下降的影响。在使用含蒽环类药物辅助治疗方案（含曲妥珠单抗或不含曲妥珠单抗和放疗）治疗的早期乳腺癌患者中，坎地沙坦联合治疗可预防早期整体左心室功能下降。
Contemporary adjuvant treatment for early breast cancer is associated with improved survival but at the cost of increased risk of cardiotoxicity and cardiac dysfunction. We tested the hypothesis that concomitant therapy with the angiotensin receptor blocker candesartan or the β-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. In a 2 × 2 factorial, randomized, placebo-controlled, double-blind trial, we assigned 130 adult women with early breast cancer and no serious co-morbidity to the angiotensin receptor blocker candesartan cilexetil, the β-blocker metoprolol succinate, or matching placebos in parallel with adjuvant anticancer therapy. The primary outcome measure was change in LVEF by cardiac magnetic resonance imaging. A priori, a change of 5 percentage points was considered clinically important. There was no interaction between candesartan and metoprolol treatments (P = 0.530). The overall decline in LVEF was 2.6 (95% CI 1.5, 3.8) percentage points in the placebo group and 0.8 (95% CI −0.4, 1.9) in the candesartan group in the intention-to-treat analysis (P-value for between-group difference: 0.026). No effect of metoprolol on the overall decline in LVEF was observed. In patients treated for early breast cancer with adjuvant anthracycline-containing regimens with or without trastuzumab and radiation, concomitant treatment with candesartan provides protection against early decline in global left ventricular function.