Kidney Cancer Journal 47 Table 2. Incidence proportions and time to event for cardiovascular events occurring in RCC patients treated with only one anti-VEGF therapy in the IMPACT database. Incidence Median Time Anti-VEGF n Events/ Proportion to Event Therapy Event NTotal (95% CI) (days) Pazopanib Only CVA 5/104 4.8% (1.6-10.9) 29 MI 3/104 2.9% (0.6-8.2) 153 TIA 3/104 2.9% (0.6-8.2) 271 TP 1/104 1% (0.02-5.2) 692 UA 1/104 1% (0.02-5.2) 580 Bevacizumab, CVA 12/556 2.2% (1.1-3.7) 122 Sorafenib or MI 25/556 4.5% (2.9-6.6) 131 Sunitinib Only TIA 8/556 1.4% (0.6-2.8) 96 TP 9/556 1.6% (0.7-3.1) 237 UA 9/556 1.6% (0.7-3.1) 337 Bevacizumab Only CVA 1/86 1.2% (0.03-6.3) 631 MI 3/86 3.5% (0.7-9.9) 338 TIA 3/86 3.5% (0.7-9.9) 161 TP 0/86 n/a n/a UA 2/86 2.3% (0.3-8.2) 324 Sorafenib Only CVA 4/84 4.8% (1.3-11.8) 96 MI 8/84 9.5% (4.2-17.9) 37 TIA 0/84 n/a n/a TP 3/84 3.6% (0.7-10.1) 561 UA 1/84 1.2% (0.03-6.5) 442 Sunitinib Only CVA 7/386 1.8% (0.7-3.7) 192 MI 14/386 3.6% (2.0-6.0) 209 TIA 5/386 1.3% (0.4-3.0) 19 TP 6/386 1.6% (0.6-3.4) 164 UA 6/386 1.6% (0.6-3.4) 363 Abbreviations: cerebrovascular accident (CVA), confidence interval (CI), myocardial infarction (MI), renal cell carcinoma (RCC), Torsades de Pointes (TP), transient ischemic attack (TIA), unstable angina (UA), vascular endothelial growth factor (VEGF) zopanib users; data for the three other drug groups are included to provide a general pattern and context for the pazopanib results. This study was not designed to estimate head-to-head comparisons of event rates between drugs. Thus, no formal drug-to-drug statistical analyses were conducted. This study was limited by the small number of subjects in several analytic groups, including the line of therapy analyses, resulting in some imprecise estimates. The estimates of effect presented are proportions; thus, assessments accounting for differing time on the prescribed agents cannot be made. Further, the IMPACT claims database lacks key cardiovascular risk factor information such as smoking, alcohol use, obesity, ethnicity, or family history. The elderly population are under-represented in the U.S. data as their healthcare is covered by Medicare. In PHARMO, out-patient pharmacy data were used to define drug exposure. As a consequence, patients starting oral anti-VEGFs during their hospital stay would not have inpatient initiation captured, thus truncating duration for the anti-VEGF drug. Further, the use of hospitalization data to identify cardiovascular outcomes may have mi s s ed events treated in an outpatient setting (such as TIA) or patients who died prior to hospitalization. A strength of this observational study is the focus on patients from two real-world population-based settings, representing drug use in the broader general population compared to clinical trial patients, where a large number of inclusion and exclusion criteria create a more select population. Cardiovascular and cerebrovascular outcomes are well captured via ICD-9 diagnosis codes in administrative data.12,13 The IMPACT database includes a large number of patients and covers a wide variety of geographic areas. Conclusions In conclusion, the frequency of selected cardiovascular events among populationbased RCC patients was similar for users of pazopanib and other anti-VEGF drugs in this study. Results from clinical trials suggest that anti-VEGF treatments may be associated with an increased risk of developing cardiovascular events among cancer patients.11 More observational epidemiologic studies of are needed to better understand this relationship in the general cancer population. Acknowledgement Page Abrahamson provided manuscript writing and editing support. This study was sponsored by GlaxoSmithKline; pazopanib is an asset of Novartis AG as of March 1, 2015. GlaxoSmithKline provided financial support for the conduct of the research and preparation of the article, including the collection, analysis and interpretation of data and writing of the report. Conflict of Interest SS, SSL, and JJN are current employees of GlaxoSmithKline; they also hold GSK shares. MvHS is an employee of the PHARMO Institute. This independent research institute performs financially supported studies for government and related healthcare authorities and several pharmaceutical companies.
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