多柔比星治疗后他汀类药物与左心室射血分数
Statins and Left Ventricular Ejection Fraction Following Doxorubicin Treatment.
作者信息
Hundley W Gregory, D'Agostino Ralph, Crotts Teresa, Craver Karen, Hackney Mary Helen, Jordan Jennifer H, Ky Bonnie, Wagner Lynne I, Herrington David M, Yeboah Joseph, Reding Kerryn W, Ladd Amy C, Rapp Stephen R, Russo Sandra, O'Connell Nathaniel, Weaver Kathryn E, Dressler Emily V, Ge Yaorong, Melin Susan A, Gudena Vinay, Lesser Glenn J
机构信息
Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond.
Department of Biostatistics and Data Science, Wake Forest School of Medicine, Winston-Salem, NC.
出版信息
NEJM Evid. 2022 Sep;1(9). doi: 10.1056/evidoa2200097. Epub 2022 Aug 18.
BACKGROUND
Statins taken for cardiovascular indications by patients with breast cancer and lymphoma during doxorubicin treatment may attenuate left ventricular ejection fraction (LVEF) decline, but the effect of statins on LVEF among patients with no cardiovascular indications is unknown.
METHODS
A double-blind, placebo-controlled, 24-month randomized trial of 40 mg of atorvastatin per day administered to patients with breast cancer and lymphoma receiving doxorubicin was conducted within the National Cancer Institute Community Oncology Research Program across 31 sites in the United States. At pretreatment and then 6 and 24 months after initiating doxorubicin, we assessed left ventricular (LV) volumes, strain, mass, and LVEF through cardiac magnetic resonance imaging, along with cognitive function and serum markers of inflammation. The primary outcome was the difference in 24-month LVEF between placebo and treatment groups, adjusted for pretreatment LVEF.
RESULTS
A total of 279 participants were enrolled in the trial. Participants had a mean (±SD) age of 49±12 years; 92% were women; and 83% were White. The mean (±SD) LVEF values were 61.7±5.5% before treatment and 57.4±6.8% at 24 months in the placebo group and 62.6±6.4% before treatment and 57.7±5.6% at 24 months in the atorvastatin group. On the basis of a multiple imputed data set for missing data and adjusted for each individual's pretreatment LVEF, 24-month declines in LVEF averaged 3.3±0.6 percentage points and 3.2±0.7 percentage points, for those randomly assigned to placebo versus statins, respectively (P=0.93). Across both treatment arms, similar percentages of individuals experienced changes of more than 10 percentage points in LVEF, LV strain, LV mass, cognition, and inflammation biomarkers, including among those with greater than 90% drug compliance.
CONCLUSIONS
In patients with breast cancer and lymphoma with no existing indication for statin therapy, prospective statin administration did not affect LVEF declines 2 years after doxorubicin. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01988571.).
背景
乳腺癌和淋巴瘤患者在接受阿霉素治疗期间服用他汀类药物用于心血管适应症，可能会减缓左心室射血分数（LVEF）下降，但他汀类药物对无心血管适应症患者的LVEF的影响尚不清楚。
方法
在美国国立癌症研究所社区肿瘤学研究项目的31个地点，对接受阿霉素治疗的乳腺癌和淋巴瘤患者进行了一项双盲、安慰剂对照、为期24个月的随机试验，每天给予40毫克阿托伐他汀。在预处理时以及开始使用阿霉素后的6个月和24个月，我们通过心脏磁共振成像评估左心室（LV）容积、应变、质量和LVEF，以及认知功能和炎症血清标志物。主要结局是安慰剂组和治疗组24个月LVEF的差异，并根据预处理时的LVEF进行调整。
结果
共有279名参与者纳入试验。参与者的平均（±标准差）年龄为49±12岁；92%为女性；83%为白人。安慰剂组治疗前的平均（±标准差）LVEF值为61.7±5.5%，24个月时为57.4±6.8%；阿托伐他汀组治疗前为62.6±6.4%，24个月时为57.7±5.6%。根据针对缺失数据的多重插补数据集，并根据每个个体的预处理LVEF进行调整，随机分配至安慰剂组和他汀类药物组的患者24个月时LVEF的平均下降分别为3.3±0.6个百分点和3.2±0.7个百分点（P=0.93）。在两个治疗组中，LVEF、LV应变、LV质量、认知和炎症生物标志物变化超过10个百分点的个体比例相似，包括药物依从性大于90%的个体。
结论
在没有他汀类药物治疗现有适应症的乳腺癌和淋巴瘤患者中，前瞻性给予他汀类药物对阿霉素治疗2年后的LVEF下降没有影响。（由美国国立卫生研究院资助；ClinicalTrials.gov编号，NCT01988571。）
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