Conover Mitchell M, Weaver James, Fan Bo, Leitz Gerhard, Richarz Ute, Li Qing, Gifkins Dina
Janssen Research & Development, Titusville, New Jersey, USA.
Prostate. 2023 May;83(7):729-739. doi: 10.1002/pros.24510. Epub 2023 Mar 6.
Cardiovascular conditions are the most prevalent comorbidity among patients with prostate cancer, regardless of treatment. Additionally, cardiovascular risk has been shown to increase following exposure to certain treatments for advanced prostate cancer. There is conflicting evidence on risk of overall and specific cardiovascular outcomes among men treated for metastatic castrate resistant prostate cancer (CRPC). We, therefore, sought to compare incidence of serious cardiovascular events among CRPC patients treated with abiraterone acetate plus predniso(lo)ne (AAP) and enzalutamide (ENZ), the two most widely used CRPC therapies.
Using US administrative claims data, we selected CRPC patients newly exposed to either treatment after August 31, 2012, with prior androgen deprivation therapy (ADT). We assessed incidence of hospitalization for heart failure (HHF), ischemic stroke, and acute myocardial infarction (AMI) during the period 30-days after AAP or ENZ initiation to discontinuation, outcome occurrence, death, or disenrollment. We matched treatment groups on propensity-scores (PSs) to control for observed confounding to estimate the average treatment effect among the treated (AAP) using conditional Cox proportional hazards models. To account for residual bias, we calibrated our estimates against a distribution of effect estimates from 124 negative-control outcomes.
The HHF analysis included 2322 (45.1%) AAP initiators and 2827 (54.9%) ENZ initiators. In this analysis, the median follow-up times among AAP and ENZ initiators (after PS matching) were 144 and 122 days, respectively. The empirically calibrated hazard ratio (HR) estimate for HHF was 2.56 (95% confidence interval [CI]: 1.32, 4.94). Corresponding HRs for AMI and ischemic stroke were 1.94 (95% CI: 0.90, 4.18) and 1.25 (95% CI: 0.54, 2.85), respectively.
Our study sought to quantify risk of HHF, AMI and ischemic stroke among CRPC patients initiating AAP relative to ENZ within a national administrative claims database. Increased risk for HHF among AAP compared to ENZ users was observed. The difference in myocardial infarction did not attain statistical significance after controlling for residual bias, and no differences were noted in ischemic stroke between the two treatments. These findings confirm labeled warnings and precautions for AAP for HHF and contribute to the comparative real-world evidence on AAP relative to ENZ.
心血管疾病是前列腺癌患者中最常见的合并症，无论接受何种治疗。此外，已有研究表明，接受某些晚期前列腺癌治疗后心血管风险会增加。对于接受转移性去势抵抗性前列腺癌（CRPC）治疗的男性，关于总体和特定心血管结局风险的证据存在冲突。因此，我们试图比较接受醋酸阿比特龙加泼尼松（AAP）和恩杂鲁胺（ENZ）这两种最广泛使用的CRPC治疗方法的患者发生严重心血管事件的发生率。
利用美国行政索赔数据，我们选择了2012年8月31日之后新接受这两种治疗之一且先前接受过雄激素剥夺治疗（ADT）的CRPC患者。我们评估了从开始使用AAP或ENZ到停药、结局发生、死亡或退出研究期间30天内心力衰竭住院（HHF）、缺血性中风和急性心肌梗死（AMI）的发生率。我们根据倾向得分（PS）对治疗组进行匹配，以控制观察到的混杂因素，使用条件Cox比例风险模型估计接受治疗（AAP）患者的平均治疗效果。为了考虑残余偏倚，我们根据124个阴性对照结局的效应估计分布对我们的估计进行校准。
HHF分析纳入了2322名（45.1%）开始使用AAP的患者和2827名（54.9%）开始使用ENZ的患者。在该分析中，开始使用AAP和ENZ的患者（PS匹配后）的中位随访时间分别为144天和122天。HHF的经验校准风险比（HR）估计值为2.56（95%置信区间[CI]：1.32，4.94）。AMI和缺血性中风的相应HR分别为1.94（95%CI：0.90，4.18）和1.25（95%CI：0.54，2.85）。
我们的研究旨在在国家行政索赔数据库中量化开始使用AAP的CRPC患者相对于ENZ患者发生HHF、AMI和缺血性中风的风险。观察到与使用ENZ的患者相比，使用AAP的患者发生HHF的风险增加。在控制残余偏倚后，心肌梗死的差异未达到统计学显著性，两种治疗方法在缺血性中风方面未观察到差异。这些发现证实了AAP关于HHF的标签警告和预防措施，并为AAP相对于ENZ的比较真实世界证据做出了贡献。
