Table 4.

Major studies for phosphodiesterase type 5 inhibitors.

Authors	Study	Study Size	Duration	Primary Endpoint	Secondary Endpoints
Sildenafil
Galie et al. [2005]	Sildenafil citrate therapy for pulmonary arterial hypertension	278	12 weeks	6MWD	mPAP, Borg dyspnea scale, WHO functional class, time to clinical worsening
Badesch et al. [2007]	Sildenafil for pulmonary arterial hypertension associated with connective tissue disease	278	12 weeks	6MWD	WHO functional class, hemodynamics
Wilkins et al. [2005]	Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study	26	16 weeks	RV mass	Hemodynamics, 6MWD, plasma BNP levels, QoL
Simonneau et al. [2008]	Addition of sildenafil to long-term intravenous epoprostenol therapy in patients with pulmonary arterial hypertension: a randomized trial	265	16 weeks	6MWD	Hemodynamics, time to clinical worsening, Borg dyspnea score, QoL
Simonneau et al. [2014]	Long-term sildenafil added to intravenous epoprostenol in patients with pulmonary arterial hypertension	242	3 years	6MWD	WHO functional class, survival status, hemodynamics
Tadalafil
Galie et al. [2009a]	Tadalafil therapy for pulmonary arterial hypertension	406	16 weeks	6MWD	WHO functional class, time to clinical worsening, Borg dyspnea score, QoL, hemodynamics
Oudiz et al. [2012]	Tadalafil for the treatment of pulmonary arterial hypertension: a double-blind 52-week uncontrolled extension study	294	52 weeks	6MWD	WHO functional class, time to clinical worsening, safety, death and survival
Galie et al. [2015a]	Initial Use of Ambrisentan plus Tadalafil in Pulmonary Arterial Hypertension	605	mean 609 days	First event of clinical failure	NT-proBNP, 6MWD, WHO functional class, Borg dyspnea index

6MWD, 6-minute walk distance; BNP, pro-brain natriuretic peptide; mPAP, mean pulmonary artery pressure; NT-proBNP, N-terminal pro-brain natriuretic peptide; QoL, quality of life; RV, right ventricular; WHO, World Health Organization.