Zhai Yinghong, Ye Xiaofei, Hu Fangyuan, Xu Jinfang, Guo Xiaojing, Cao Yang, Lin Zhen, Zhou Xiang, Guo Zhijian, He Jia
School of Medicine, Tongji University, Shanghai, China.
Department of Health Statistics, Second Military Medical University, Shanghai, China.
Front Cardiovasc Med. 2021 Sep 27;8:735466. doi: 10.3389/fcvm.2021.735466. eCollection 2021.
Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings. To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities. This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals. The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC/ROR = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications ( = 1,301, 38.61%), embolic and thrombotic events ( = 821, 24.36%), and cardiac failure ( = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC/ROR = 1.33/2.59), followed by pulmonary hypertension (IC/ROR = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1-Q3: 4-85 days) for ischemic heart disease, with the longest time being 68 days (Q1-Q3: 21-139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC/ROR = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%). Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.
卡非佐米是一种用于治疗复发难治性多发性骨髓瘤的有效蛋白酶体抑制剂，已与大量心血管事件相关。然而，在实际临床环境中，与该药物相关的心血管并发症模式仍未得到充分描述。为了进一步深入了解卡非佐米相关心血管毒性的发生频率、范围、临床特征、发作时间和结局，本不成比例（病例/非病例）研究利用了2014年至2019年FAERS数据库中的记录。心血管事件通过标准化医学术语词典查询（SMQs）的狭义版本进行定义并大致分为八个类别。计算报告比值比（ROR）和信息成分（IC）以衡量不成比例性。此外，应用统计收缩法以减少假阳性信号。最终纳入的记录数为28479963条，其中3370条记录涉及卡非佐米相关的心血管事件。在整个数据库中进行探索时，发现卡非佐米给药与心血管事件之间存在显著的不成比例关联（IC/ROR = 0.85/1.95）。进一步分析发现，所有八大类心血管毒性均与卡非佐米存在不成比例的关联，其发生频率、发病时间和严重程度各不相同。心肌病相关并发症（n = 1301，38.61%）、栓塞和血栓形成事件（n = 821，24.36%）以及心力衰竭（n = 765，22.70%）在报告的问题中占很大比例。值得注意的是，心力衰竭的信号最强（IC/ROR = 1.33/2.59），其次是肺动脉高压（IC/ROR = 1.19/2.34）。心血管事件的中位发病时间为41天（第一四分位数 - 第三四分位数：9 - 114天），缺血性心脏病的最短中位时间为16天（第一四分位数 - 第三四分位数：4 - 85天），栓塞和血栓形成事件的最长时间为68天（第一四分位数 - 第三四分位数：21 - 139天）。尖端扭转型室速/QT间期延长被确定为一种新的并发症（IC/ROR = 0.33/1.29），特别值得注意的是其最高的死亡比例（44.11%）。使用卡非佐米治疗可导致严重且多样的心血管事件。早期和强化监测很重要，尤其是在开始使用卡非佐米后的前3个月。在最大化卡非佐米益处的同时减少其潜在心血管危害应成为首要任务。
