What question did this study set out to answer?

Investigate the impact of hydroxyurea therapy compared to chronic transfusions on pulmonary hypertension and mortality in sickle cell disease.

May 20, 2026

A65-05 Pulmonary Hypertension and Mortality in Adults With Sickle Cell Disease: Impact of Hydroxyurea Therapy vs. Chronic Transfusions

Key Points

Investigate the impact of hydroxyurea therapy compared to chronic transfusions on pulmonary hypertension and mortality in sickle cell disease.
Data collected from TriNetX US Collaborative Network across 73 health care organizations.
Cohorts included adults aged 18-65 with sickle cell disease receiving chronic transfusions (n=1,119) or hydroxyurea therapy (n=4,332).
Propensity score matching (1:1) was employed to balance demographics and laboratory variables.
Patients receiving transfusions had a 1.45× higher risk of pulmonary hypertension compared to hydroxyurea users (95% CI 1.24-1.69).
Hydroxyurea group had a significant PH-free survival rate of 76.9% compared to 68.6% in transfusion patients (log-rank p < 0.001).
All-cause mortality was similar: 4.6% in hydroxyurea vs. 5.6% in transfusions (p = 0.29).

Abstract

Abstract Rationale Pulmonary hypertension (PH) is a serious and often fatal complication of sickle cell disease (SCD), driven by chronic hemolysis, endothelial dysfunction, and vascular remodeling. Disease-modifying therapies such as hydroxyurea (HU) and chronic transfusions may alter this risk through distinct mechanisms. HU increases fetal hemoglobin and improves anemia, potentially providing vascular protection. Comparative data between HU and transfusions regarding PH and mortality remain limited. Methods We used the TriNetX US Collaborative Network (73 health care organizations) to identify adults aged 18-65 with SCD (ICD-10 D57) and crisis episodes who underwent PH screening (echocardiography or right heart catheterization). Two cohorts were defined: (1) chronic transfusions (≥3 transfusions within 3 years; n = 1,119) and (2) HU therapy (use within 3 years; n = 4,332). Propensity score matching (1:1) was used to balance demographics and laboratory variables (n = 1,117 per group). Outcomes included incident PH (ICD-10 I27.x) and all-cause mortality. Risk ratios, odds ratios, hazard ratios, and Kaplan-Meier survival analyses were performed. Results Transfusion patients had a 1.45× higher risk of PH (95% CI 1.24-1.69) and 1.62× higher odds (95% CI 1.33-1.98) compared with HU users. PH-free survival significantly favored the HU group (log-rank p 0.001), with 76.9% of HU-treated patients vs. 68.6% of transfusion patients remaining PH-free. Mean PH events were similar among those who developed PH (8.44 ± 14.0 vs. 9.62 ± 14.7; p = 0.35). All-cause mortality was 4.6% in HU vs. 5.6% in transfusion patients (risk difference 1.0%, 95% CI -0.8 to 2.8; p = 0.29). The hazard ratio for death was 1.13 (95% CI 0.78-1.64; p = 0.06), with overlapping survival curves (p = 0.51). Conclusions Hydroxyurea was associated with a lower risk of pulmonary hypertension and improved PH-free survival compared with chronic transfusion therapy, consistent with its vascular protective effects. No significant difference in mortality was observed, likely due to limited follow-up and competing risks in the SCD population. These findings support further prospective and mechanistic studies to clarify the role of HU in PH prevention and long-term cardiopulmonary outcomes. This abstract is funded by: None

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