Inpatient and outpatient treatment patterns of cancer-associated thrombosis in the United States

This retrospective cohort study utilized three real-world databases: (1) IQVIA Hospital Charge Data Master (CDM) database, (2) IQVIA Patient Centric Pharmacy Claims Database (LRx), and (3) IQVIA Patient Centric Medical Claims Database (Dx) from January 1, 2015 to May 31, 2018.

The CDM database was used to identify anticoagulant therapies received during an inpatient or ED visit. It is comprised of data collected from hospital operational files from over 650 non-federal, acute-care short-stay hospitals. Data elements include all inpatient and outpatient encounters with detailed information on diagnoses, procedures, treatment, and patient and hospital characteristics.

The LRx database was used to identify anticoagulants received from outpatient pharmacies. It consists of pharmacy claims for dispensed prescriptions collected from pharmacies covering approximately 90% of all dispensed prescriptions from US retail pharmacies and over 1.4 billion prescriptions per year, representing claims from all payer types. The Dx database was used to identify anticoagulant treatments administered during outpatient physician office visits. It is composed of approximately 1 billion outpatient medical claims per year submitted by over 860,000 practitioners in the US.

In compliance with the Health Insurance Portability and Accountability Act (HIPAA), patient data were de-identified and, therefore, informed consent and institutional review board (IRB) review were unnecessary.

Patients with CAT were identified during an inpatient or ED visit in CDM between 7/1/2015 and 4/30/2018. Adult patients (age ≥ 18) with a hospital admission or ED visit with primary discharge diagnosis of DVT or PE (an approach that has been shown to have positive predictive value for identifying VTE of 95%; 95% CI 93–97) [17, 18] were included. The first eligible inpatient or ED visit was defined as the index hospital visit and the admission date as the index date. Patients were linked to LRx and Dx, and had evidence of cancer during the 6-months prior to, on, or within 30 days after the index date. Evidence of cancer was defined as (1) ≥ 1 inpatient claim with a cancer diagnosis; (2) ≥ 2 outpatient medical claims with a diagnosis code for the same cancer type; or (3) ≥ 1 outpatient medical claim with a cancer diagnosis and ≥ 1 medical or pharmacy claim for cancer treatment (chemotherapy, biologic treatment, cancer-related hormone therapy, radiation, or cancer-related surgery). Diagnosis codes were identified in CDM and Dx using International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9/10-CM) codes. Cancer treatments were identified in Dx and LRx using Current Procedural Terminology (CPT) codes, Healthcare Common Procedure Coding Systems (HCPCS) Level II codes, and/or National Drug Codes (NDCs). Cancer-related surgery was captured in CDM using CPT codes. Patients with atrial fibrillation/flutter or mechanical heart value during the 6-months before or during the index hospital visit; or inferior vena cava filter or pregnancy during the study period were excluded.  Patients had 6 months of data availability before the index date and ≥ 1 month of follow-up after the discharge date (Fig. 1). Baseline characteristics were assessed during the 6-month pre-index period and on the index date. Details are provided in Table 1.

Anticoagulants used during the index hospital visit were captured from billing descriptions in CDM. The index CAT treatment was defined as the first anticoagulant observed. Six treatment groups were formed: (1) DOACs (apixaban, edoxaban, dabigatran, rivaroxaban), (2) LMWH (dalteparin sodium, enoxaparin sodium, fondaparinux sodium, tinzaparin sodium), (3) warfarin (warfarin sodium), (4) UFH (heparin sodium), (5) thrombolytic agents (alteplase, urokinase), and (6) no anticoagulant treatment. If LMWH or UFH were observed on the same date as an oral anticoagulant, the patient was grouped into the specified oral anticoagulant subgroup (e.g., a patient with LMWH and a DOAC on the same date was classified as a DOAC patient). If LMWH and UFH were observed on the same date, the patient was grouped into the LMWH subgroup.

The first outpatient anticoagulant received within 3 months after discharge was captured from the Dx and LRx databases in patients with ≥ 3 months of continuous follow-up after discharge. Sensitivity analyses were conducted in patients with ≥ 1 and ≥ 6 months of follow-up. Results of sensitivity analyses are available in supplemental tables and figures.

Outpatient anticoagulant treatment patterns were evaluated in patients with ≥ 3 months of follow-up after discharge and ≥ 3 months of follow-up after initiation of the outpatient therapy. Discontinuation, persistence, and adherence were measured. Discontinuation was defined as a gap > 60 days between the end of days’ supply of a prescription and the next dispensing date of any drug in the same treatment group or as a switch to a new treatment group; discontinuation date was defined as the dispensing date + days’ supply for the prescription before the gap. Persistence was defined as remaining on therapy with no gaps > 60 days between the end of days’ supply for a prescription to the next dispensing date of any drug in the same treatment group. The proportion of patients with persistence to the initial outpatient treatment of ≥ 3 months was reported. Adherence was assessed using medication possession ratio (MPR), calculated as the sum of the days’ supply of all claims occurring before the discontinuation date divided by the number of days between the treatment start date and discontinuation date, and capped at 100%. Adherence was defined as MPR ≥ 80%.

This study was descriptive in nature. Mean and standard deviation (SD) were presented as measures of central tendency and variance for continuous variables. Frequency (N) and percentage (%) of patients in each cohort were reported for categorical variables. All analyses were conducted using SAS version 9.4 (Cary, NC, USA).