Outcomes of pulmonary vasodilator use in Veterans with pulmonary hypertension associated with left heart disease and lung disease

Abstract

Randomized trials of pulmonary vasodilators in pulmonary hypertension (PH) due to left heart disease (Group 2) and lung disease (Group 3) have demonstrated potential for harm. Yet these therapies are commonly used in practice. Little is known of the effects of treatment outside of clinical trials. We aimed to establish outcomes of vasodilator treatment for Groups 2/3 PH in real-world practice. We conducted a retrospective cohort study of 132,552 Medicare-eligible Veterans with incident Groups 2/3 PH between 2006-2016, and a secondary nested case-control study. Our primary outcome was a composite of death by any cause or selected acute organ failures. In our cohort analysis, we calculated adjusted risks of time to our outcome using Cox proportional hazards models with facility-specific random effects. In our case-control analysis, we used logistic mixed-effects models to estimate the effect of any past, recent, and cumulative exposure on our outcome. From our cohort study, 3,249 (2.5%) Veterans were exposed to pulmonary vasodilators. Exposure to vasodilators was associated with increased risk of our primary outcome, in both Group 3 (HR 1.58 [95% CI 1.37-1.82]) and Group 2 (HR 1.26 [1.12-1.41]) PH patients. The case-control study determined odds of our outcome increased by 11% per year of exposure (OR 1.11 [1.07-1.16]). Treating Groups 2/3 PH with vasodilators in clinical practice is associated with increased risk of harm. This extension of trial findings to a real-world setting offers further evidence to limit use of vasodilators in Groups 2/3 PH outside of clinical trials.

Heart Disease and Stroke Statistics—2023 Update: A Report From the American Heart Association

“…A comprehensive study of data from 132 552 veterans with PH diagnosed in groups 2 and 3 found a 39% increased mortality or organ failure in those exposed to pulmonary vasodilators (HR, 1.31 [95% CI, 1.25–1.37]). 141…”

Real‐world evidence to advance knowledge in pulmonary hypertension: Status, challenges, and opportunities. A consensus statement from the Pulmonary Vascular Research Institute's Innovative Drug Development Initiative's Real‐world Evidence Working Group

“…50 Algorithms that are multicomponent and include the presence of PAH medications, diagnostic codes, and procedural codes improve performance. 50,52,53 The development and validation of algorithms outside of Group 1 PH are especially challenging in part because therapies approved for the treatment of PAH are used on and off-label for the treatment of other PH groups (e.g., PH in interstitial lung disease, chronic thromboembolic pulmonary hypertension [CTEPH]). Compounded with the lack of specificity in diagnostic codes, researchers are limited in their ability to discriminate patients within the five clinical classification groups in claims data.…”

Pulmonary Vascular Research Institute GoDeep: A meta‐registry merging deep phenotyping datafrom international PH reference centers

“…3 Worldwide, PH Group 2 is thought to affect 5%-10% of elderly individuals (>65 years), 3 and indepth analyzes reveal that PH Group 3 encompasses another very large group of PH, far outnumbering Group 1 patients. 4 Global epidemiological data indicate that approximately 20% of all hospitalized patients might present with some variant of PH or pulmonary pressure elevation. 5 Taken together, these findings support the contention that PH is substantially more prevalent than commonly assumed and constitutes a comorbidity of global significance.…”

“…Usually considered a rare disease, due to the historical focus on idiopathic PAH (IPAH), current estimates calculate an age‐dependent PH prevalence of about 1% of the global population, which increases up to 10% in the elderly 3 . Worldwide, PH Group 2 is thought to affect 5%–10% of elderly individuals (>65 years), 3 and in‐depth analyzes reveal that PH Group 3 encompasses another very large group of PH, far outnumbering Group 1 patients 4 . Global epidemiological data indicate that approximately 20% of all hospitalized patients might present with some variant of PH or pulmonary pressure elevation 5 .…”