B106-16 Midodrine-Associated Increased Mortality Risk in Patients With Pulmonary Arterial Hypertension

Rationale Midodrine, an alpha-1 adrenergic agonist, is commonly used to manage orthostatic hypotension and has been increasingly prescribed in patients with cardiovascular conditions. While its vasopressor effects may theoretically increase afterload, the impact of midodrine on outcomes in patients with pulmonary arterial hypertension (PAH) remains largely unknown. We aim to evaluate the association between midodrine use and all-cause mortality in patients with PAH. Methods We used the TriNetX platform to identify cohorts and perform statistical analysis. We included adult patients (>18 years) diagnosed with PAH (ICD-10 I27.0) after January 1st, 2000, stratified into two groups. Group A (Midodrine) comprised patients using midodrine; Group B (Non-Midodrine) comprised those who did not. Patients with heart failure (ICD-10 I50) or secondary pulmonary hypertension (ICD-10 I27.2) were excluded. The primary outcome was all-cause mortality at 1-year follow-up. The index event was defined as the first day meeting all criteria: PAH diagnosis and midodrine initiation for Group A, and PAH diagnosis for Group B. We performed propensity score matching, accounting for demographics and multisystem comorbidities (cardiovascular, respiratory, endocrine, genitourinary, and other major categories). After matching, each group comprised 569 individuals. After excluding patients with outcomes prior to the study window, 559 remained in Group A and 564 in Group B. Results At 1-year follow-up, 169 (30.2%) in Group A died versus 55 (9.8%) in Group B, representing a 20.5% absolute risk increase (RR 3.10, 95% CI 2.341-4.106, p < 0.001). Odds ratio was 4.01 (95% CI 2.878-5.587, p < 0.001). Conclusions Midodrine use in PAH was associated with significantly increased all-cause mortality at 1-year follow-up, suggesting potential harm in this population. While propensity score matching minimized confounding, residual confounding by disease severity or unmeasured variables cannot be excluded. The 20.5% absolute risk increase translates to a number needed to harm of approximately 5. This finding warrants careful risk-benefit consideration when prescribing midodrine to PAH patients and raises important safety concerns. Prospective studies are needed to determine if this reflects drug-related harm or unmeasured confounding by disease severity.