Table 3.
Patients, etiology, end points, treatment effects, and adverse reactions of the US Food and Drug Administration approved phosphodiesterase type-5 inhibitors in the pivotal Phase III randomized controlled trials for treatment of pulmonary arterial hypertension in adults.
| SUPER-1 [32] | PHIRST [33] | |
|---|---|---|
| Patients (no.) | 278 | 405 |
| Drug | Sildenafil | Tadalafil |
| Dosing/route | 20, 40 or 80 mg tid/os | 2.5, 10, 20, or 40 mg qd/os |
| Follow-up (months) | 3 | 4 |
| Etiology (%)* | ||
| IPAH | 64 | 60 |
| CTD | 30 | 24 |
| CHD | 6 | 11 |
| Anorexigen use | — | 4 |
| Functional class | ||
| NYHA/WHO II | 36 | 34 |
| NYHA/WHO III | 61 | 62 |
| NYHA/WHO IV | 3 | 2 |
| Primary end point | 6MWD | 6MWD |
| Treatment effects | ||
| Δ6MWD (m) | 45, 46, and 50 | 14, 20, 27 and 33† |
| Hemodynamics | Improved | Improved¶ |
| Clinical worsening | Reduced | Reduced# |
| Adverse reactions | Epistaxis, headache, dyspepsia, flushing | Headache, myalgia, back pain, flushing |
SUPER: Sildenafil Use in Pulmonary artERial hypertension; PHIRST: Pulmonary Arterial HypertensIon and ReSponse to Tadalafil; tid: three times daily; os: oral; qd: once-daily; *sum of percentage may not be 100% for rounding to the nearest unit; 0.5 is rounded to the upper unit; IPAH: idiopathic pulmonary arterial hypertension; CTD: connective tissue disease; CHD: congenital heart disease (systemic-to-pulmonary shunts); NYHA: New York Heart Association; WHO: World Health Organization; 6MWD: 6 min walk distance; Δ: mean (or median) change from baseline; †only the 40 mg dose met the prespecified level of statistical significance (P < 0.01); ¶improvements were observed only with 20 and 40 mg doses in mean pulmonary arterial pressure and pulmonary vascular resistance; #only the 40 mg dose improved the time to clinical worsening, incidence of clinical worsening, and quality of life.