Cardiovascular Imaging Research Center, Division of Cardiology, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston.
Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston.
JAMA. 2023 Aug 8;330(6):528-536. doi: 10.1001/jama.2023.11887.
Anthracyclines treat a broad range of cancers. Basic and retrospective clinical data have suggested that use of atorvastatin may be associated with a reduction in cardiac dysfunction due to anthracycline use.
To test whether atorvastatin is associated with a reduction in the proportion of patients with lymphoma receiving anthracyclines who develop cardiac dysfunction.
DESIGN, SETTING, AND PARTICIPANTS: Double-blind randomized clinical trial conducted at 9 academic medical centers in the US and Canada among 300 patients with lymphoma who were scheduled to receive anthracycline-based chemotherapy. Enrollment occurred between January 25, 2017, and September 10, 2021, with final follow-up on October 10, 2022.
Participants were randomized to receive atorvastatin, 40 mg/d (n = 150), or placebo (n = 150) for 12 months.
The primary outcome was the proportion of participants with an absolute decline in left ventricular ejection fraction (LVEF) of ≥10% from prior to chemotherapy to a final value of <55% over 12 months. A secondary outcome was the proportion of participants with an absolute decline in LVEF of ≥5% from prior to chemotherapy to a final value of <55% over 12 months.
Of the 300 participants randomized (mean age, 50 [SD, 17] years; 142 women [47%]), 286 (95%) completed the trial. Among the entire cohort, the baseline mean LVEF was 63% (SD, 4.6%) and the follow-up LVEF was 58% (SD, 5.7%). Study drug adherence was noted in 91% of participants. At 12-month follow-up, 46 (15%) had a decline in LVEF of 10% or greater from prior to chemotherapy to a final value of less than 55%. The incidence of the primary end point was 9% (13/150) in the atorvastatin group and 22% (33/150) in the placebo group (P = .002). The odds of a 10% or greater decline in LVEF to a final value of less than 55% after anthracycline treatment was almost 3 times greater for participants randomized to placebo compared with those randomized to atorvastatin (odds ratio, 2.9; 95% CI, 1.4-6.4). Compared with placebo, atorvastatin also reduced the incidence of the secondary end point (13% vs 29%; P = .001). There were 13 adjudicated heart failure events (4%) over 24 months of follow-up. There was no difference in the rates of incident heart failure between study groups (3% with atorvastatin, 6% with placebo; P = .26). The number of serious related adverse events was low and similar between groups.
Among patients with lymphoma treated with anthracycline-based chemotherapy, atorvastatin reduced the incidence of cardiac dysfunction. This finding may support the use of atorvastatin in patients with lymphoma at high risk of cardiac dysfunction due to anthracycline use.
ClinicalTrials.gov Identifier: NCT02943590.
蒽环类药物治疗广泛的癌症。基础和回顾性临床数据表明，使用阿托伐他汀可能与减少蒽环类药物引起的心脏功能障碍有关。
测试阿托伐他汀是否与减少接受蒽环类药物化疗的淋巴瘤患者中心脏功能障碍的比例有关。
设计、地点和参与者：在美国和加拿大的 9 个学术医疗中心进行的双盲随机临床试验，纳入了 300 名计划接受基于蒽环类药物化疗的淋巴瘤患者。招募于 2017 年 1 月 25 日至 2021 年 9 月 10 日进行，最终随访于 2022 年 10 月 10 日进行。
参与者随机接受阿托伐他汀，40mg/d（n=150）或安慰剂（n=150）治疗 12 个月。
主要结局是从化疗前到 12 个月时左心室射血分数（LVEF）绝对值下降≥10%且最终值<55%的参与者比例。次要结局是从化疗前到 12 个月时 LVEF 绝对值下降≥5%且最终值<55%的参与者比例。
300 名随机参与者（平均年龄 50[标准差 17]岁；142 名女性[47%]）中，286 名（95%）完成了试验。在整个队列中，基线平均 LVEF 为 63%（标准差 4.6%），随访 LVEF 为 58%（标准差 5.7%）。91%的参与者注意到了研究药物的依从性。在 12 个月的随访中，有 46 名（15%）的 LVEF 从化疗前下降≥10%，最终值<55%。阿托伐他汀组的主要终点发生率为 9%（13/150），安慰剂组为 22%（33/150）（P=0.002）。与安慰剂组相比，接受蒽环类药物治疗后 LVEF 下降≥10%且最终值<55%的参与者接受阿托伐他汀治疗的可能性几乎高出 3 倍（比值比，2.9；95%置信区间，1.4-6.4）。与安慰剂相比，阿托伐他汀还降低了次要终点的发生率（13% vs 29%；P=0.001）。在 24 个月的随访中有 13 例（4%）经裁决的心衰事件。研究组之间新发心衰的发生率无差异（阿托伐他汀组 3%，安慰剂组 6%；P=0.26）。严重相关不良事件的数量较少且两组相似。
在接受基于蒽环类药物化疗的淋巴瘤患者中，阿托伐他汀降低了心脏功能障碍的发生率。这一发现可能支持在因蒽环类药物使用而有心脏功能障碍高风险的淋巴瘤患者中使用阿托伐他汀。
ClinicalTrials.gov 标识符：NCT02943590。
