Tadalafil is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5), the enzyme responsible for the breakdown of cyclic guanosine monophosphate (cGMP). It is already available as Cialis for the treatment of erectile dysfunction.
In patients with PAH, release of nitric oxide by the vascular endothelium is impaired, which results in reduced levels of cGMP in the pulmonary vascular smooth muscle. Tadalafil increases cGMP concentrations, leading to vasodilation of the pulmonary vascular bed.1
In a double-blind, pivotal study, investigators randomised 405 patients with PAH to receive placebo or tadalafil (2.5mg, 10mg, 20mg, or 40mg) orally once daily for 16 weeks. Approximately half the patients were already receiving background therapy with the endothelin receptor antagonist bosentan.
Tadalafil increased the distance walked in 6 minutes (the primary endpoint) in a dose-dependent manner; only the 40mg dose met the prespecified level of statistical significance (p<0.01). In the 79 patients receiving the 40mg dose who underwent postbaseline assessment, the mean placebo-corrected treatment effect was an improvement of 33 metres (95% CI 15–50 metres).2
- Adcirca Summary of Product Characteristics, November 2010.
- Galiè N et al. Circulation 2009; 119: 2894-903.
Further information: Lilly