背景:据报道,在SEAS(辛伐他汀和依泽替米贝治疗主动脉瓣狭窄)试验中,有1,873名患者使用辛伐他汀/依泽替米贝治疗恶性肿瘤的风险增加。
目的:本研究的目的是在更大样本量的急性冠脉综合征后稳定下来的患者中阐明这一意外发现。我们在IMPROVE-IT(改善降低结局:Vytorin疗效国际试验)中对恶性肿瘤事件进行了前瞻性系统分析.
方法:在IMPROVE-IT中,在服用≥1剂研究药物的辛伐他汀40mg的背景下,将17,708例急性冠脉综合征后患者随机分为依泽替米贝10mg或匹配的安慰剂。研究者报告的可疑肿瘤(良性和恶性)或从不良事件审查中确定的可疑肿瘤由肿瘤学家在不了解药物分配的情况下裁定。原发性恶性肿瘤终点包括新的,复发,或进行性恶性肿瘤(不包括非黑色素皮肤恶性肿瘤)。次要终点是恶性肿瘤导致的死亡。
结果:在本试验中,1,470例患者在中位6年的随访中出现了原发性恶性肿瘤终点。最常见的恶性肿瘤部位是前列腺(18.9%),肺(16.8%),和膀胱(8.8%),治疗组之间没有差异(每个位置p>0.05)。Kaplan-Meier7年恶性肿瘤发生率与依泽替米贝和安慰剂相似(10.2%vs.10.3%;危险比:1.03;95%置信区间:0.93至1.14;p=0.56),恶性肿瘤死亡率也是如此(3.8%vs.3.6%;风险比:1.04;95%置信区间:0.88~1.23;p=0.68)。
结论:在每天接受辛伐他汀40mg的17,708名患者中,在中位随访6年(96,377例患者-年)期间,与接受安慰剂组相比,随机接受每日10mg依泽替米贝的患者的恶性肿瘤发生率和因恶性肿瘤死亡的死亡率相似.(IMPROVE-IT:检查患有急性冠脉综合征的受试者的结果:维托林[依泽替米贝/辛伐他汀]与辛伐他汀[P04103];NCT00202878)。
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.
OBJECTIVE: 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).