对17708例随机接受依折麦布与安慰剂治疗的患者进行恶性肿瘤的前瞻性评估：来自IMPROVE-IT研究的分析
Prospective Evaluation of Malignancy in 17,708 Patients Randomized to Ezetimibe Versus Placebo: Analysis From IMPROVE-IT.
作者信息
Giugliano Robert P, Gencer Baris, Wiviott Stephen D, Park Jeong-Gun, Fuchs Charles S, Goessling Wolfram, Musliner Thomas A, Tershakovec Andrew M, Blazing Michael A, Califf Robert, Cannon Christopher P, Braunwald Eugene
机构信息
TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Smilow Cancer Hospital at Yale New Haven, New Haven, Connecticut, USA.
出版信息
JACC CardioOncol. 2020 Sep 15;2(3):385-396. doi: 10.1016/j.jaccao.2020.07.008. eCollection 2020 Sep.
BACKGROUND
An increased risk of malignancy was reported with simvastatin/ezetimibe in 1,873 patients in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) trial.
OBJECTIVES
The purpose of this study was to clarify this unexpected finding in a larger sample size of patients stabilized after acute coronary syndrome, we conducted a prospective systematic analysis of malignancy events in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial).
METHODS
Within IMPROVE-IT, 17,708 patients post-acute coronary syndrome were randomized to either ezetimibe 10 mg or matching placebo on a background of simvastatin 40 mg who took ≥1 dose of the study drug. Suspected tumors (benign and malignant) reported by investigators or identified from a review of adverse events were adjudicated by oncologists without knowledge of drug assignment. The primary malignancy endpoint included new, relapsing, or progressive malignancies (excluding nonmelanotic skin malignancies). The secondary endpoint was death due to malignancy.
RESULTS
In this trial, 1,470 patients developed the primary malignancy endpoint during a median 6 years of follow-up. The most common malignancy locations were prostate (18.9%), lung (16.8%), and bladder (8.8%) with no differences by treatment group (p > 0.05 for each location). Kaplan-Meier 7-year rates of malignancies were similar with ezetimibe and placebo (10.2% vs. 10.3%; hazard ratio: 1.03; 95% confidence interval: 0.93 to 1.14; p = 0.56), as were the rates for malignancy death (3.8% vs. 3.6%; hazard ratio: 1.04; 95% confidence interval: 0.88 to 1.23; p = 0.68).
CONCLUSIONS
Among 17,708 patients receiving simvastatin 40 mg daily, those randomized to ezetimibe 10 mg daily had a similar incidence of malignancy and deaths due to malignancy compared with those receiving placebo during a median follow-up of 6 years (96,377 patient-years). (IMPROVE-IT: Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin [Ezetimibe/Simvastatin] vs Simvastatin [P04103]; NCT00202878).
背景
在SEAS（辛伐他汀与依折麦布治疗主动脉瓣狭窄）试验中，1873例患者使用辛伐他汀/依折麦布后被报道患恶性肿瘤风险增加。
目的
本研究旨在通过更大样本量的急性冠脉综合征后病情稳定的患者来阐明这一意外发现，我们对IMPROVE-IT（改善预后：Vytorin疗效国际试验）中的恶性肿瘤事件进行了前瞻性系统分析。
方法
在IMPROVE-IT试验中，17708例急性冠脉综合征后患者在服用≥1剂研究药物的情况下，以40mg辛伐他汀为基础，被随机分为10mg依折麦布组或匹配的安慰剂组。由研究者报告或通过不良事件审查确定的疑似肿瘤（良性和恶性）由肿瘤学家在不知药物分配情况的前提下进行判定。主要恶性肿瘤终点包括新发、复发或进展性恶性肿瘤（不包括非黑素瘤皮肤恶性肿瘤）。次要终点是因恶性肿瘤导致的死亡。
结果
在本试验中，1470例患者在中位6年的随访期间出现主要恶性肿瘤终点。最常见的恶性肿瘤发生部位是前列腺（18.9%）、肺（16.8%）和膀胱（8.8%），各治疗组之间无差异（每个部位p>0.05）。依折麦布组和安慰剂组的Kaplan-Meier 7年恶性肿瘤发生率相似（10.2%对10.3%；风险比：1.03；95%置信区间：0.93至1.14；p = 0.56），恶性肿瘤死亡发生率也相似（3.8%对3.6%；风险比：1.04；95%置信区间：0.88至1.23；p = 0.68）。
结论
在17708例每日服用40mg辛伐他汀的患者中，在中位6年（96377患者年）的随访期间，随机分配至每日服用10mg依折麦布组的患者与服用安慰剂组的患者相比，恶性肿瘤发生率和因恶性肿瘤导致的死亡发生率相似。（IMPROVE-IT：急性冠脉综合征患者的结局研究：Vytorin[依折麦布/辛伐他汀]对比辛伐他汀[P04103]；NCT00202878）
Zotero 插件