Time to combination therapy for sildenfail monotherapy in pulmonary artery hypertension (PAH). A comparison with the reported experience with bosentan

Background In New Zealand sildenafil is first line therapy for Class I, IV and V PAH with WHO Class III and IV symptoms. Combination therapy (CT) with an endothelin receptor antagonist (ERA) or inhaled iloprost is approved by a national panel, for worsening symptoms and a decline in 6MW and RHC hemodynamics. Objectives To analyze time between start of sildenafil monotherapy (MT) and addition of a second agent to treat PAH in a cohort of patients on sildenafil 50mg tds monotherapy. To report 6MW results, WHO class and RHC hemodynamic profiles from baseline and prior to initiation of CT. Results 107 patients with PAH were included: 82 (76.6% were female). Diagnosis: IPAH 40 (37.4%), CTD 31 (29%) CHD 7 (6.5%) CTEPH 15 (14%) and PoPH 8 (7.5%) Mean age at diagnosis 48 years. The median time to diagnosis 38.43 weeks (range: 1-613 weeks). 46 patients required additional therapy. Median time to CT was 73.21 weeks (range: 4-327) weeks. 33/46 were on sildenafil + ERA and 13/46 sildenafil + iloprost. The 6MW and RHC hemodynamics are summarized below, these differences were not significant. There was a significant decline in WHO class p=0.016 prior to initiation of CT. Change in 6MW and RHC on Mono therapy 6MW RA mPA CO PVR MT Baseline (89) 347 (178) 8 (7) 50 (12.5) 3.8 (1.5) 10.4 (5) CT Baseline (23) 315 (190) 9 (9) 56 (15) 3.8 (1.4) 12.4 (7) Results are presented as median and IQR n = 89 for hemodynamics at MT baseline and 23 at CT baseline Conclusion This unique group of patients includes Class I, IV and V PH commenced on sildenafil MT had a similar time to CT (73.2 weeks/18.2 months) as reported with bosentan in other studies (18-20 months).