title: Claims analysis of hypertension occurrence, severity changes and patterns of antihypertensive use in cancer patients receiving vascular endothelial growth factor inhibitors.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA Kaiser Permanente Colorado, Lafayette, CO, USA lisa.thompson@kp.org.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Thompson
authors.affiliation: 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.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Saseen
authors.affiliation: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
authors.forename: Cindy L
authors.initials: CL
authors.lastname: O'Bryant
authors.affiliation: PeakStat, Aurora, CO, USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Allen
authors.affiliation: Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA.
authors.forename: Kavita V
authors.initials: KV
authors.lastname: Nair
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000175:diagnosis / Q000453:epidemiology*; D007345:Insurance Claim Review / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy / Q000453:epidemiology*; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Vascular endothelial growth factor inhibitor; cardiac complication; hypertension