The Influence of Pulmonary Vasodilator Therapy on Outcomes in Veterans with Pulmonary Hypertension Due to Left Heart Disease Open Access

Abstract

Background: Pulmonary hypertension (PH) is a state of elevated blood pressure in the pulmonary circulation, which increases morbidity and mortality regardless of underlying etiology and is most common in patients with left-sided heart disease. While pulmonary vasodilator therapies are effective for pulmonary arterial hypertension (PAH; "PAH-targeted therapy"), benefit in PH due to left-sided heart disease (PH-LHD) is relatively understudied. We hypothesized that PAH-targeted therapy is used in a small proportion of veterans with PH-LHD and has no impact on survival.

Methods: We utilized national data from the Veterans Health Administration Corporate Data Warehouse to identify a cohort of veterans with PH diagnosed between 01/01/2003 and 09/30/2015. We extracted data on demographics, comorbidities, diagnostic evaluation, use of PAH-targeted therapy and death. By using comorbid conditions, we identified the subtype of PH. The propensity for PAH-targeted therapy use was evaluated in multivariable logistic regression models. The effect of treatment on death was estimated using multivariable Cox proportional hazards analyses using covariates, using propensity score, and using propensity matching to account for confounding by indication of the treatment effect.

Results: We identified 110,564 veterans diagnosed with PH during the study period. Patients were mostly male (96%), had median age 70.2 years, and had median follow-up of 2.85 years. Left heart disease was the only comorbidity associated with PH in 16%. Of veterans with PH-LHD, 2.9% received treatment with PAH-targeted therapy and had a median time from PH diagnosis to death of 5.21 years compared to 3.88 years in veterans never treated with PAH-targeted therapy; unadjusted hazard ratio 0.74, 95% confidence interval: 0.65, 0.82. No benefit of PAH-targeted therapy on risk of death was observed when adjusted for confounding covariates or propensity score.

Conclusions: Using administrative and clinical data of veterans receiving care in the Veterans Health Affairs system, we identified a large cohort with PH, many of whom have PH-LHD. We showed that PAH-targeted therapy is used in a minority of patients with PH-LHD and has no effect on survival when accounting for baseline differences between treated and untreated subjects. Further investigation into whether this therapy is associated with other benefits or risks, such as difference in hospitalization frequency, is warranted.

Table of Contents

INTRODUCTION .............................................................................................................. 1

BACKGROUND ................................................................................................................ 3

METHODS ......................................................................................................................... 5

RESULTS ......................................................................................................................... 11

DISCUSSION ................................................................................................................... 16

REFERENCES ................................................................................................................. 22

TABLES / FIGURES ........................................................................................................... i

Table 1: Schema for classification of pulmonary hypertension in veterans by ICD-9 diagnosis code usage. ................................................................................................... i

Table 2. Characteristics of U.S. veterans with pulmonary hypertension receiving care in the Veteran Health Administration system, 01/01/2003-09/30/2015. ............ ii

Table 3. Characteristics of U.S. veterans (2003-2015) with pulmonary hypertension due to left-sided heart disease, compared to all veterans with pulmonary hypertension. .............................................................................................................. iv

Table 4. Effect of PAH-targeted treatment vs. no treatment on death in veterans with PH-LHD. ..................................................................................................................... v

Table 5: Hazard ratio for death for selected covariates, all veterans with PH. .......... vi

Figure 1. Study diagram of retrospective cohort study to evaluate subtypes, treatment and outcome of veterans with pulmonary hypertension. PH, pulmonary hypertension; PAH, pulmonary arterial hypertension; misc, miscellaneous. ........... vii

Figure 2. Models for Cox proportional hazards analysis. ........................................ viii

Figure 3. Cohort flow diagram for study. .................................................................. ix

Figure 4. Kaplan-Meier survival curve for veterans with pulmonary hypertension, stratified by subtype, unadjusted................................................................................. x

Figure 5: Kaplan-Meier survival curve for veterans with pulmonary hypertension due to left heart disease, stratified by treatment status, unadjusted. .......................... xi

Figure 6: Differences between treated and untreated patients and effect on balancing of selected covariates by propensity matching. ........................................................ xii

Figure 7. Kaplan-Meier survival curve for veterans with pulmonary hypertension diagnosed between 01/01/2003 and 09/30/2015 and receiving care in the VHA system. ..................................................................................................................... xiii

Figure 8: Kaplan-Meier survival curve for veterans with pulmonary hypertension, stratified by treatment status, unadjusted. Includes all veterans with PH. ............... xiv

About this Master's Thesis

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School	Laney Graduate School
Department	Clinical Research
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Medicine and Surgery Health Sciences, Epidemiology
Keyword	retrospective cohort study epidemiology pulmonary arterial hypertension pulmonary hypertension survival mortality pulmonary vascular disease
Committee Chair / Thesis Advisor	Hart, C. Michael, Emory University
Committee Members	Plantinga, Laura, Emory University Klein, Mitchel, Emory University

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