Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol

Aims: 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 {beta}-blocker metoprolol will alleviate the decline in left ventricular ejection fraction (LVEF) associated with adjuvant, anthracycline-containing regimens with or without trastuzumab and radiation. Methods and results: In a 2 x 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 {beta}-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. Conclusion: 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

Peso à cobrição e ganho de peso durante a gestação de cabras nativas, exóticas e mestiças no semi-árido Mating weight and weight gain during gestation of native, exotic and crossbred goats in the semi-arid

Avaliaram-se os efeitos de mês, ano, ordem de parto e tipo de parto sobre o peso à cobrição (PC) e o ganho de peso durante a gestação (GP), respectivamente, de 753 e 527 cabras nativas Canindés, 463 e 333 cabras exóticas Anglo-nubianas, 374 e 296 Alpinas, 151 e 87 de mestiças ½ Alpina (A) ½ Sem Raça Definida (SRD), 92 e 73 ¾ Alpina (A) ¼ SRD, criadas na Estação Experimental de Pendência - EMEPA-PB, Soledade-PB, na microrregião semi-árida da Paraíba, em regime semi-intensivo, no período de 1980 a 1994. O mês foi significativo sobre os pesos à cobrição das matrizes Canindés, Anglo-nubianas, ½ A ½ SRD e ¾ A ¼ SRD. O ano influenciou o PC de todos os grupos genéticos. O efeito do ano sobre o GP foi significativo para as cabras Canindés, Anglo-nubianas, ½ A ½ SRD e Alpinas. O peso à cobrição elevou-se com o aumento da ordem de parto e o GP foi mais evidente entre as cabras de primeiro parto. O tipo de parto foi significativo sobre o GP das matrizes nubianas, ¾ A ¼ SRD e Alpina, que tiveram maiores ganhos quando pariram apenas um cabrito. A raça influenciou o PC e o GP de todas as matrizes. A raça nativa foi a mais leve e com o melhor ganho de peso; as exóticas, as mais pesadas e com GP inferiores aos da raça Canindé e da mestiça ½ A ½ SRD; e a mestiça ¾ A ¼ SRD, a raça com peso corporal (PC) e GP semelhantes às exóticas. Concluiu-se que a composição genética dos animais e os fatores ambientais, como mês, ano, ordem e tipo de parto, refletiram sobre o peso à cobrição e o ganho de peso durante a gestação das matrizes estudadas.<br>The effects of month, year, order and type parturition on mating weight (MW), weight gain during gestation (WG), respectively, of 753 and 527 Caninde native goats, 463 and 333 exotic Anglo Nubian and 374 and 296 Alpine goats, 151 and 87 crossbred ½ Alpine ½ SRD, and 92 and 73 ¾Alpine ¼SRD goats, raised in the Experimental Station of the Governmental Research Institute (EMEPA-PB), Soledade - Paraiba - Brazil, in the period from 1980 to 1994. The effect of month was significant on MW of the Caninde, Anglo Nubian and crossbred goats. The year influenced MW of all genetic groups and effect on WG was significant for Caninde, Anglo Nubian, ½A ½SRD and Alpine goats. Mating weight increased as parturition order increased and WG was evident in the goats of first kidding. Type parturition showed significant effect on WG of Nubian, ¾ A ¼ SRD and Alpine goats, that showed higher WG when had single kidding. Significant difference among genetic groups was observed for MW and WG. The native goats were more weightless than the exotic and crossbred goats, however showed better weight gain during gestation. There was superiority of mating weights of exotic than the native and crossbred goats. The animal genetic composition and environmental factors, as month, year, order and type of birth, affected mating weight and weight gain during the gestation of the studied flock