PURPOSE: Geriatric patients with pulmonary arterial hypertension (PAH) may have a poorer prognosis than younger patients because of increased comorbidities. Tadalafil, a phosphodiesterase-5 inhibitor, appeared safe and efficacious in patients with PAH in a 16-week, double-blind, placebo-controlled trial. Here we report safety and efficacy with tadalafil in geriatric patients compared with patients < 65 years of age during this trial.
METHODS: A post-hoc subgroup analysis was performed with geriatric patients (N=112) randomized to placebo or 2.5-, 10-, 20- or 40-mg tadalafil (n=25, 24, 22, 22, and 19, respectively). Safety and efficacy was assessed by adverse events (AE), six-minute walk distance (6MWD) and clinical worsening (death, lung transplantation, atrial septostomy; new chronic PAH treatment, worsening WHO functional class or hospitalization for worsening PAH) at week 16, compared to baseline.
RESULTS: For subjects ≥65 years treated with tadalafil 40-mg, mean change in 6MWD was numerically higher compared with placebo (35.4 m and 8.1 m, respectively) at week 16. Patients < 65 years experienced a mean change of 43 m (P< 0.05) on tadalafil 40-mg compared with 10 m on placebo. The percentage of patients with clinical worsening at week 16 was numerically lower in tadalafil 40-mg group (5%) compared with placebo (16%) for both patient groups (≥65 and < 65 years). For patients ≥65 years, the most common AE in tadalafil 40-mg group was headache (32%), compared to placebo (12%). For patients < 65 years, 45% experienced headache on tadalafil 40-mg compared with 16% on placebo. There were no AEs leading to discontinuation in tadalafil 40-mg group, compared with 20% AE-related discontinuations in placebo-treated patients.
CONCLUSION: Although caution is indicated in interpreting a post-hoc subgroup analysis with relatively small sample size, in geriatric patients with PAH, 40-mg tadalafil treatment over a 16-week period appeared to result in an increase in 6MWD and a decrease in clinical worsening compared with placebo. There were no AE-related discontinuations in geriatric patients on tadalafil 40-mg.
CLINICAL IMPLICATIONS: Tadalafil may provide a safe and effective treatment in elderly patients with PAH.
DISCLOSURE: Carl Arneson, Employee Dr. Arneson and Ms. McDevitt are paid employees of United Therapeutics.; No Product/Research Disclosure Information