Thompson Lisa A, Saseen Joseph J, O'Bryant Cindy L, Allen Richard R, Nair Kavita V
Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA Kaiser Permanente Colorado, Lafayette, CO, USA
Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA Department of Family Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
J Oncol Pharm Pract. 2015 Aug;21(4):258-67. doi: 10.1177/1078155214530177. Epub 2014 Apr 11.
Vascular endothelial growth factor inhibitors such as bevacizumab, sorafenib, and sunitinib are utilized in the treatment of multiple cancers. Although these agents are associated with hypertension, there is a lack of evidence describing patterns of antihypertensive use in patients with vascular endothelial growth factor inhibitor-associated hypertension in a non-trial, "real-world" setting.
To describe the occurrence and severity of vascular endothelial growth factor inhibitor-associated hypertension, patterns of antihypertensive use and occurrence of cardiovascular complications in a non-trial population, and to describe patterns of initial antihypertensive therapy in patients developing hypertension during treatment with a vascular endothelial growth factor inhibitor.
This retrospective cohort study utilized claims data from the Medstat MarketScan Commercial Claims and Encounter database to identify patients with claims for a vascular endothelial growth factor inhibitor and a diagnosis of cancer using International Classification of Diseases, 9th Revision, Clinical Modification codes, Healthcare Common Procedure Coding System J-codes and National Drug Codes. The study period encompassed claims from one year before the patient's first claim for a vascular endothelial growth factor inhibitor, and continued through one year after the initial vascular endothelial growth factor inhibitor claim. Patients meeting study criteria were classified into cohorts A1, patients with no hypertension throughout the study period; A2, patients without hypertension at baseline who developed hypertension after starting a vascular endothelial growth factor inhibitor; and cohort B, patients with hypertension prior to receiving a vascular endothelial growth factor inhibitor. We utilized medical and pharmacy claims data to describe the presence of hypertension, its severity, and the occurrence of cardiovascular complications throughout the study period. Initial antihypertensive use in cohort A2 was described.
In all, 2177 patients met study criteria and were categorized into cohorts A1 (n = 708), A2 (n = 333) and B (n = 1136). Approximately 32% of patients without hypertension at baseline had claims suggestive for hypertension during the study period. Life-threatening (Grade 4) hypertension increased throughout the study period for cohorts A1, A2, and B, to 3.4%, 10.2%, and 16.4%, respectively (p < 0.001 for all). Claims suggestive of Grade 3 hypertension occurred in more patients in cohort B (45.8%) than in cohort A2 (32.7%, p < 0.001). Cardiovascular complications occurred in 4.7%, 15.6%, and 22.7% of patients in cohorts A1, A2, and B, respectively. Initial antihypertensive agent selection did not impact the occurrence of cardiovascular complications in cohort A2.
Our study provides valuable insight into non-trial patterns of vascular endothelial growth factor inhibitor-associated hypertension occurrence and severity, and is consistent with prior claims analysis. Identification of optimal strategies to manage vascular endothelial growth factor inhibitor-associated hypertension remain to be clarified with the advent of more comprehensive data sets.
血管内皮生长因子抑制剂,如贝伐单抗、索拉非尼和舒尼替尼,被用于多种癌症的治疗。尽管这些药物与高血压有关,但在非试验性的“真实世界”环境中,缺乏关于血管内皮生长因子抑制剂相关高血压患者抗高血压药物使用模式的证据。
描述血管内皮生长因子抑制剂相关高血压的发生情况和严重程度、非试验人群中抗高血压药物的使用模式和心血管并发症的发生情况,并描述在接受血管内皮生长因子抑制剂治疗期间发生高血压的患者的初始抗高血压治疗模式。
这项回顾性队列研究利用了Medstat MarketScan商业索赔和病历数据库中的索赔数据,通过国际疾病分类第九版临床修订代码、医疗保健通用程序编码系统J代码和国家药品代码,识别出有血管内皮生长因子抑制剂索赔且诊断为癌症的患者。研究期涵盖患者首次提出血管内皮生长因子抑制剂索赔前一年的索赔,并持续到首次提出血管内皮生长因子抑制剂索赔后的一年。符合研究标准的患者被分为A1组,即整个研究期间无高血压的患者;A2组,即基线时无高血压但在开始使用血管内皮生长因子抑制剂后出现高血压的患者;以及B组,即接受血管内皮生长因子抑制剂治疗前患有高血压的患者。我们利用医疗和药房索赔数据来描述整个研究期间高血压的存在情况、严重程度以及心血管并发症的发生情况。描述了A2组的初始抗高血压药物使用情况。
共有2177名患者符合研究标准,并被分为A1组(n = 708)、A2组(n = 333)和B组(n = 1136)。基线时无高血压的患者中,约32%在研究期间有提示高血压的索赔。A1组、A2组和B组中,危及生命(4级)的高血压在整个研究期间均有所增加,分别增至3.4%、10.2%和16.4%(所有p < 0.001)。B组中提示3级高血压的索赔患者(45.8%)多于A2组(32.7%,p < 0.001)。A1组、A2组和B组中分别有4.7%、15.6%和22.7%的患者发生心血管并发症。A2组中初始抗高血压药物的选择并未影响心血管并发症的发生。
我们的研究为血管内皮生长因子抑制剂相关高血压的非试验性发生模式和严重程度提供了有价值的见解,与先前的索赔分析一致。随着更全面数据集的出现,管理血管内皮生长因子抑制剂相关高血压的最佳策略仍有待明确。