Abstract

Introduction

It is crucial to assess clinical benefit and bleeding risk when selecting an anticoagulant for patients with venous thromboembolism (VTE). This study examined the incidence of major bleeding and non-major bleeding and clinical predictors of major bleeding among patients with VTE in the usual clinical practice setting.

Methods

VTE patients aged ≥18 years were identified from the Truven Health MarketScan commercial or Medicare supplemental insurance database. Index date was defined as the first VTE diagnosis between 07/01/2006 – 12/31/2011. Patients were required to have ≥2 VTE outpatient diagnoses within a 3-week window or have 1 VTE diagnosis in an inpatient setting, have a continuous health plan enrollment for 6 months prior to the index date (baseline), and have no VTE diagnosis in the baseline period. Major bleeding was defined as any bleeding that resulted in hospitalization or blood transfusion; all other bleeds were non-major bleeding. Patients were followed until major bleeding/non-major bleeding, death, disenrollment, or end of study. Multivariate Cox regression was used to examine factors associated with major bleeding.

Results

Of 267,655 eligible patients, 182,972 patients were with deep vein thrombosis (DVT) only (68.4%), 69,169 with pulmonary embolism (PE) only (25.8%); and 15,514 with both (5.8%). Mean age was 61.5 years, and 53.1% were female. Mean follow-up period was 17.3 months (median=12.1). The annual incidence of major bleeding and non-major bleeding were 3.9% and 20.1%, respectively. The median time to major bleeding from index VTE diagnosis was 2.2 months. Major risk factors at baseline for major bleeding (Risk increase>20%) were history of major bleeding (HR=10.78, 95%CI=10.30-11.28) and non-major bleeding (HR=1.61, 95%CI=1.54-1.68), chemotherapy (HR=1.27, 95%CI=1.20-1.35), age ≥65 vs.≤40 years (HR=1.27, 95%CI=1.18-1.37), alcohol abuse (HR=1.26, 95%CI=1.16-1.38), cancer (HR=1.25, 95%CI=1.19-1.31), and heart disease (HR=1.23, 95%CI=1.18-1.28) (Table). Baseline hormone therapy (HR=0.74, 95%CI=0.68-0.80) and pregnancy (HR=0.59, 95%CI=0.46-0.74) were associated with reduced risk for major bleeding.

Table

Demographical and clinical factors associated with major bleeding in patients with VTE

HR95% CIP-value
Type of VTE     
 DVT Only Reference 
 PE Only 1.01 0.97 1.05 .6894 
 DVT and PE 0.81 0.75 0.88 <.0001 
Age, years     
18-40 Reference 
41-65 1.16 1.08 1.25 <.0001 
65+ 1.27 1.18 1.37 <.0001 
Male 0.99 0.95 1.02 .3728 
Baseline Comorbid Conditions     
Charlson Comorbidity Index Score 1.09 1.08 1.10 <.0001 
Cancer 1.25 1.19 1.31 <.0001 
Heart Disease 1.23 1.18 .28 <.0001 
Peripheral Arterial Disease 0.99 0.91 1.09 .9032 
Diabetes 1.08 1.04 1.13 <.0001 
Hypertension 1.05 1.01 1.09 .0088 
Ischemic Stroke 1.17 1.12 1.23 <.0001 
Systemic Embolism 1.05 0.94 1.17 .3693 
Thrombophilia 1.17 1.08 1.28 .0002 
Catheter Ablation 0.96 0.92 1.01 .1385 
Obesity 0.95 0.86 1.04 .2478 
Alcohol Abuse 1.26 1.16 1.38 <.0001 
Atrial Fibrillation 0.96 0.91 1.01 .1095 
Fracture/Trauma 1.07 1.03 1.11 .0004 
Pregnancy 0.59 0.46 0.74 <.0001 
Major Bleeding 10.78 10.30 11.28 <.0001 
Non-major Bleeding 1.61 1.54 1.68 <.0001 
Baseline Medications     
Anti-Platelet Therapy 1.08 1.03 1.14 .0040 
NSAIDs Medication 0.92 0.89 0.95 <.0001 
 Antidepressants 1.04 1.00 1.08 .0533 
Hormone Therapy 0.74 0.68 0.80 <.0001 
 Chemotherapy 1.27 1.20 1.35 <.0001 
HR95% CIP-value
Type of VTE     
 DVT Only Reference 
 PE Only 1.01 0.97 1.05 .6894 
 DVT and PE 0.81 0.75 0.88 <.0001 
Age, years     
18-40 Reference 
41-65 1.16 1.08 1.25 <.0001 
65+ 1.27 1.18 1.37 <.0001 
Male 0.99 0.95 1.02 .3728 
Baseline Comorbid Conditions     
Charlson Comorbidity Index Score 1.09 1.08 1.10 <.0001 
Cancer 1.25 1.19 1.31 <.0001 
Heart Disease 1.23 1.18 .28 <.0001 
Peripheral Arterial Disease 0.99 0.91 1.09 .9032 
Diabetes 1.08 1.04 1.13 <.0001 
Hypertension 1.05 1.01 1.09 .0088 
Ischemic Stroke 1.17 1.12 1.23 <.0001 
Systemic Embolism 1.05 0.94 1.17 .3693 
Thrombophilia 1.17 1.08 1.28 .0002 
Catheter Ablation 0.96 0.92 1.01 .1385 
Obesity 0.95 0.86 1.04 .2478 
Alcohol Abuse 1.26 1.16 1.38 <.0001 
Atrial Fibrillation 0.96 0.91 1.01 .1095 
Fracture/Trauma 1.07 1.03 1.11 .0004 
Pregnancy 0.59 0.46 0.74 <.0001 
Major Bleeding 10.78 10.30 11.28 <.0001 
Non-major Bleeding 1.61 1.54 1.68 <.0001 
Baseline Medications     
Anti-Platelet Therapy 1.08 1.03 1.14 .0040 
NSAIDs Medication 0.92 0.89 0.95 <.0001 
 Antidepressants 1.04 1.00 1.08 .0533 
Hormone Therapy 0.74 0.68 0.80 <.0001 
 Chemotherapy 1.27 1.20 1.35 <.0001 

Note: VTE=Venous thromboembolism; DVT= Deep vein thrombosis; PE=Pulmonary embolism

HR=Hazard ratio; CI=Confidence interval

Conclusions

Major and non-major bleeding were common in patients with VTE. Multiple factors, especially history of bleeding, age≥65 years, alcohol abuse, cancer and heart disease, were associated with increased risk for major bleeding. Further research needs to examine bleeding risk associated with anticoagulant therapy.

Disclosures:

Liu:Pfizer: Employment, Equity Ownership. Xie:StatInMed: Employment, Research Funding. Phatak:BMS: Employment, Equity Ownership. Mardekian:Pfizer: Employment, Equity Ownership. Tan:Pfizer: Employment, Equity Ownership. Baser:StatInMed: Employment, Research Funding. Ramacciotti:BMS: Employment, Equity Ownership.

Author notes

*

Asterisk with author names denotes non-ASH members.