背景:聚(ADP-核糖)聚合酶(PARP)抑制剂(PARPi)在各种肿瘤中提供了显着的抗肿瘤活性,主要携带BRCA1/BRCA2基因的有害突变。关于此类药物的心脏和血管安全性的数据很少。我们进行了一项荟萃分析,以评估主要不良心血管事件(MACEs)的发生率和相对风险(RR)。高血压,以PARPi为基础治疗的实体瘤患者的血栓栓塞事件。
方法:通过搜索Medline/PubMed,科克伦图书馆,和ASCO会议摘要。根据系统评价和荟萃分析的首选报告项目(PRISMA)声明进行数据提取。综合赔率比(OR),RR,95%置信区间(CI)使用固定效应或随机效应方法计算,取决于研究的异质性。采用RevManMeta分析软件(v.5.2.3)进行统计学分析。
结果:选择了32项研究进行最终分析。任何高等级的PARPi相关MACEs的发生率为5.0%和0.9%,分别,与控制武器的3.6%和0.9%相比,对应于任何级别的MACEs的风险显着增加(PetoOR1.62;P=0.0009),但不属于高级别(P=0.49)。PARPi的任何级别和高级别高血压的发生率分别为17.5%和6.0%,分别,与对照组的12.6%和4.4%相比。用PARPi治疗显着增加任何级别的高血压的风险(随机效应,RR=1.53;P=0.03),但等级不高(随机效应,RR=1.47;P=0.09)与对照组相比。最后,与对照组相比,基于PARPi的治疗显着增加了任何级别(PetoOR=1.49,P=0.004)而非高级别(PetoOR=1.31;P=0.13)的血栓栓塞事件的风险。
结论:基于PARPi的治疗与MACEs的风险显着增加有关,高血压,与对照组相比,任何级别的血栓栓塞事件。高级别事件的风险没有显著增加,以及这些不良事件的绝对低发生率,导致不考虑在无症状患者中推荐的常规心血管监测。
Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) provided significant antitumor activity in various tumors, mainly carrying deleterious mutations of BRCA1/BRCA2 genes. Only few data are available regarding the cardiac and vascular safety profile of this drug class. We carried out a meta-analysis for assessing the incidence and relative risk (RR) of major adverse cardiovascular events (MACEs), hypertension, and thromboembolic events in patients with solid tumors treated with PARPi-based therapy.
Prospective studies were identified by searching the Medline/PubMed, Cochrane Library, and ASCO Meeting abstracts. Data extraction was conducted according to the Preferred Reporting Items for Systematic
review and Meta-Analyses (PRISMA) statement. Combined odds ratios (ORs), RRs, and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods, depending on studies heterogeneity. RevMan software for meta-analysis (v.5.2.3) was used to carry out statistical analyses.
Thirty-two studies were selected for the final analysis. The incidence of PARPi-related MACEs of any and high grade was 5.0% and 0.9%, respectively, compared with 3.6% and 0.9% in the control arms, corresponding to a significant increased risk of MACEs of any grade (Peto OR 1.62; P = 0.0009) but not of high grade (P = 0.49). The incidence of hypertension of any grade and high grade was 17.5% and 6.0% with PARPi, respectively, compared with 12.6% and 4.4% in the controls. Treatment with PARPi significantly increased the risk of hypertension of any grade (random-effects, RR = 1.53; P = 0.03) but not of high grade (random-effects, RR = 1.47; P = 0.09) compared with controls. Finally, PARPi-based therapies significantly increased the risk of thromboembolic events of any grade (Peto OR = 1.49, P = 0.004) and not of high grade (Peto OR = 1.31; P = 0.13) compared with controls.
PARPi-based therapy is associated with a significantly increased risk of MACEs, hypertension, and thromboembolic events of any grade compared with controls. The lack of a significant increased risk of high-grade events together with the absolute low incidence of these adverse events led not to consider routine cardiovascular monitoring as recommended in asymptomatic patients.