Results from the previously published, multicenter, randomized,
placebo-controlled, 16-week Pulmonary Arterial Hypertension and Response
to Tadalafil (PHIRST) study linked treatment with tadalafil 40 mg
(Adcirca, Lilly) — the highest of four doses evaluated — to
significantly improved 6-minute walk distance, time to clinical
worsening and quality of life.
To evaluate the long-term safety and durability of efficacy of tadalafil
in patients with pulmonary arterial hypertension, researchers conducted
PHIRST-2 — a double blind, uncontrolled extension study in which
patients were randomly assigned to receive once-daily tadalafil 20 mg
(n=63) or 40 mg (n=294) for an additional 52 weeks.
Patients who received tadalafil 20 mg or 40 mg in both PHIRST and
PHIRST-2 maintained improvements in 6-minute walk distances achieved
during PHIRST (406 m and 413 m, respectively) at the conclusion of the
extension study (415 m and 410 m, respectively). Those previously
receiving lower doses or placebo during PHIRST, however, did not
experience a similar level of improvement.
A higher proportion of patients receiving tadalafil 20 mg experienced
WHO functional class deterioration when compared with those assigned
tadalafil 40 mg (9% vs. 6
.
Post-hoc analyses associated background bosentan (Tracleer, Actelion)
use and higher 6-minute walk distance at PHIRST baseline with fewer
clinical worsening events.
Safety profiles from both PHIRST and PHIRST-2 were comparable, according
to the study results. Ninety-two percent of patients experienced at
least one treatment-emergent adverse event during PHIRST-2, 49% of which
may have been drug-related. Most adverse events, however, were mild to
moderate in intensity and did not result in study discontinuation.
“These data demonstrate that the long-term safety profile of tadalafil
appears similar to that in the 16-week PHIRST study and that treatment
for up to 68 weeks appears safe and well tolerated,” the researchers
wrote. “For patients receiving [tadalafil 20 mg] or [tadalafil 40 mg],
the short-term improvements in exercise capacity observed in PHIRST
appeared to be maintained for an additional 52 weeks in PHIRST-2.”
