Comparative Effectiveness of Endovascular and Pharmacologic Treatment Pathways in Non-Diabetic Peripheral Arterial Disease Patients Using Administrative Claims Data Öffentlichkeit

Abstract

BACKGROUND: Peripheral Arterial Disease (PAD) is a chronic disease affecting 12 million Americans in which plaque accumulates in the femoral, popliteal, tibial, or peroneal arteries, causing claudication, leg weakness, and conditions threatening limb viability like gangrene. Recent trends suggest increased usage of endovascular interventions as second-line therapy over pharmacologic treatments. As surgical procedures introduce safety risks, a comparative effectiveness study of second-line endovascular interventions against second-line pharmacologic treatment was performed to determine the risk of requiring lower limb amputation or peripheral arterial bypass (primary endpoint) and the risk of cardiovascular, ischemic, and mortality-related events (safety endpoint).

METHODS: Patients with PAD who had undergone first-line pharmacologic therapy (statins, clopidogrel, or aspirin) but required second-line therapy of either cilostazol, percutaneous transluminal angioplasty (PTA) with stent, or PTA with atherectomy between January 1, 2011 and December 31, 2016 were selected from three administrative claims data sets ("OPTUM," "MDCR," "CCAE"). Analyses were restricted to non-diabetic patients, due to confounding of outcomes and treatment patterns by diabetes status. Pairwise comparisons of two PTA-based treatment pathways were conducted against one cilostazol treatment pathway. Propensity score matching was implemented to adjust for all known confounders. Cox proportional hazards models were generated to assess risk. Empirical calibration of traditional p-values adjusted for the data sets' inherent systemic error.

RESULTS: The PTA-based treatment pathways consistently produced effect estimates suggesting elevated risk of requiring amputation or bypass compared to the cilostazol treatment pathway. In two of the three data sets, PTA with stent had statistically significant effects (OPTUM, HR 1.92, 95% CI [1.07, 3.47], traditional p = 0.03, calibrated p = 0.049; MDCR, HR 2.37, 95% CI [1.33, 4.31], traditional p = 0.004, calibrated p = 0.001). MDCR produced a statistically significant effect for PTA with atherectomy (HR 1.90, 95% CI [1.01, 3.75], traditional p = 0.054, calibrated p = 0.024). No statistically significant effects were observed for the safety endpoint.

CONCLUSIONS: A potential two-fold increase in lower limb amputation or peripheral arterial bypass was observed in patients receiving PTA with stent compared to those treated with cilostazol. No meaningful difference in risk was evident for the safety endpoint.

Table of Contents

Abstract...........................................................................................iv

Acknowledgements..........................................................................vi

Table of Contents.............................................................................vii

List of Abbreviations........................................................................xiii

Chapter 1: Background.....................................................................1

Introduction..............................................................................1

Arteriosclerosis and Atherosclerosis..............................................1

Peripheral Arterial Disease...........................................................2

PAD Classification Systems..................................................4

PAD Outcomes...........................................................................5

Outcome: Peripheral Arterial Bypass.....................................6

Outcome: Lower Limb Amputation........................................6

Outcome: Myocardial Infarction and Ischemic Stroke..............7

Outcome: Death................................................................8

PAD Prevalence and Incidence.....................................................8

PAD Risk Factors.......................................................................8

Risk Factor: Age...............................................................9

Risk Factor: Race and Ethnicity...........................................9

Risk Factor: Smoking........................................................10

Risk Factor: Diabetes........................................................11

PAD Diagnosis..........................................................................12

PAD Treatments.......................................................................14

First-Line Therapies..........................................................14

Second-Line Therapies......................................................15

Study Objectives......................................................................17

Primary Objective............................................................18

Secondary Objective........................................................18

Chapter 2: Methods.......................................................................19

Exposures of Interest...............................................................19

Primary Endpoint.....................................................................19

Safety Endpoint.......................................................................19

Study Inclusion Criteria and Setting...........................................19

Study Design..........................................................................22

Data Sets...............................................................................24

Modelling and Tools.................................................................26

OMOP Common Data Model and OHDSI Analytic Packages....26

Chapter 3: Statistical Analysis......................................................30

Feature Extraction...................................................................30

Covariate Settings..........................................................30

Covariate Selection.........................................................31

Propensity-Score Matching.......................................................32

Outcome Modelling.................................................................32

Negative Controls...................................................................33

Chapter 4: Results.......................................................................35

Cohort Characterization..........................................................35

Propensity Score Matching......................................................44

Survival Time........................................................................47

Outcome Models (Uncalibrated)...............................................48

Negative Controls..................................................................49

Outcome Models (Empirically Calibrated)..................................50

OPTUM.........................................................................51

MDCR..........................................................................52

CCAE...........................................................................53

Chapter 5: Discussion..................................................................54

Summary..............................................................................54

Strengths and Study Limitations..............................................55

Conclusion............................................................................57

Supplementary Tables and Figures..............................................59

Project Code..........................................................................59

Concept Sets.........................................................................59

Cilostazol......................................................................59

PTA with Stent...............................................................59

PTA with Atherectomy.....................................................60

PAD..............................................................................64

Aspirin..........................................................................65

Diabetes........................................................................65

Statins..........................................................................65

Clopidogrel....................................................................65

Covariate Settings and Exclusions.............................................66

Covariate Imbalance...............................................................67

Covariate Balance Plots...........................................................69

OPTUM.........................................................................69

MDCR...........................................................................70

CCAE...........................................................................71

Preference Plots.....................................................................72

OPTUM.........................................................................72

MDCR..........................................................................74

CCAE...........................................................................76

Attrition Diagrams.................................................................78

OPTUM........................................................................78

MDCR..........................................................................82

CCAE...........................................................................86

Survival Time.......................................................................90

OPTUM........................................................................90

MDCR.........................................................................92

CCAE..........................................................................94

Kaplan-Meier Plots................................................................96

OPTUM........................................................................96

MDCR.........................................................................98

CCAE..........................................................................100

Forest Plots.........................................................................102

OPTUM.......................................................................102

MDCR.........................................................................103

CCAE.........................................................................104

Negative Controls................................................................105

Empirical Calibration Plots.....................................................109

OPTUM.......................................................................109

MDCR.........................................................................111

CCAE..........................................................................113

References.................................................................................115

About this Master's Thesis

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School	Rollins School of Public Health
Department	Executive Masters of Public Health
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Pharmacy Health Sciences, Epidemiology
Stichwort	pharmacoepidemiology OHDSI claims propensity score matching OMOP empirical calibration peripheral arterial disease
Committee Chair / Thesis Advisor	Binongo, Jose N, Emory University
Committee Members	Gaydos, Laurie, Emory University Yoo, Andrew, Johnson & Johnson, Inc.
Partnering Agencies	Does not apply (no collaborating organization)

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