Long-term use of sildenafil in inoperable chronic thromboembolic pulmonary hypertension.
BACKGROUND
There are currently no licensed medical therapies for inoperable chronic thromboembolic pulmonary hypertension (CTEPH).


METHODS
In this double-blind, placebo-controlled pilot study, 19 subjects with inoperable CTEPH were randomly assigned to sildenafil or placebo for 12 weeks. The primary end point was change in 6-min walking distance (6MWD). Secondary end points included changes in World Health Organization (WHO) class, cardiopulmonary hemodynamics, quality of life (QOL) scores, and N-terminal pro brain natriuretic peptide (NT-proBNP). All subjects were transferred to open-label sildenafil at the end of the study and offered repeat assessment at 12 months.


RESULTS
There were no significant differences between the two groups with respect to change in exercise capacity. However significant improvements were seen in WHO class and pulmonary vascular resistance (PVR). Seventeen subjects were eligible for reassessment at 12 months and demonstrated significant improvements in 6MWD, activity and symptom components of QOL, cardiac index, PVR, and NT-proBNP.


CONCLUSIONS
Although this pilot study was insufficiently powered to test the primary end point, it did suggest beneficial effects in favor of sildenafil in several secondary end points at both 3 months and 12 months. Further larger-scale trials of sildenafil in inoperable CTEPH are required to confirm these findings and potentially increase the treatment options available for this devastating disease.


BACKGROUND
The study protocol was registered with the UK National Research Register database (publication ID N0542136603).
Suntharalingam
Jay
J
Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
Treacy
Carmen M
CM
Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
Doughty
Natalie J
NJ
Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
Goldsmith
Kimberley
K
MRC Biostatistics Unit, Cambridge.
Soon
Elaine
E
Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
Toshner
Mark R
MR
Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
Sheares
Karen K
KK
Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
Hughes
Rodney
R
Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire.
Morrell
Nicholas W
NW
University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, UK.
Pepke-Zaba
Joanna
J
Pulmonary Vascular Diseases Unit, Pulmonary Vascular Diseases Unit, Papworth Hospital, Cambridgeshire. Electronic address: joanna.pepkezaba@papworth.nhs.uk.
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010879:Piperazines / Q000008:administration & dosage*; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011687:Purines / Q000008:administration & dosage; D011788:Quality of Life; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D016896:Treatment Outcome; D014655:Vascular Resistance; D014665:Vasodilator Agents / Q000008:administration & dosage*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate