TABLE 3.
RANDOMIZED CLINICAL TRIALS IN PAH WITH HRQoL AS SECONDARY OUTCOME
| Year | Reference | Intervention | N | Design | Etiology of PAH | NYHA Class | Follow-up Interval | 6MWD Change | Instrument(s) Used | HRQoL Findings |
|---|---|---|---|---|---|---|---|---|---|---|
| 1996 | (37) | Epoprostenol | 81 | Randomized, open-label, controlled | IPAH | III, IV | 12 wk | 113m | NHP, CHQ | Significant improvement in all 4 domains of CHQ, 2 of 6 domains of NHP |
| 2002 | (38) | Iloprost | 203 | Randomized, placebo-controlled | IPAH, CTD, AA, CTEPH | III, IV | 12 wk | 36m | EQ-5D utility index and VAS, SF-12 | Significant improvement in EQ-5D VAS. Nonsignificant trend in EQ-5D utility index. No change in SF-12. |
| 2002 | (39) | Treprostinil | 470 | Randomized, double-blind, placebo-controlled | IPAH, CTD, CHD | II, III, IV | 12 wk | 16m | MLHFQ | Significant improvement in physical dimension score of MHLFQ. Nonsignificant trend in total MHLFQ score. |
| 2003 | (40) | Beraprost | 116 | Randomized, double-blind, placebo-controlled | IPAH, CTD, CHD | II, III | 3, 6 mo | 22-31m | MLHFQ | No significant improvement in total MLHFQ or subscores. |
| 2004 | (41) | Sildenafil | 22 | Randomized, double-blind, crossover | IPAH | II, III | 6 wk | 44%↑ exercise time | CHQ | Significant improvement in dyspnea and fatigue domains of CHQ. Nonsignificant trend in emotional domain. |
| 2004 | (42) | Sitaxsentan | 178 | Randomized, double-blind, placebo-controlled | IPAH, CTD, CHD | II, III, IV | 12 wk | 33-35m | SF-36 | No significant differences in SF-36. |
| 2004 | (43) | Treprostinil | 90 | Post hoc analysis of RCT | CTD | II, III, IV | 12 wk | 21m | MLHFQ | Nonsignificant trend toward improvement in physical dimension score of MLHFQ. |
| 2005 | (44) | Ambrisentan | 64 | Randomized, double-blind, dose-ranging | IPAH, CTD, HIV, AA | II, III | 12 wk | 36m | VAS | Significant improvement in VAS compared to baseline. |
| 2005 | (45) | Sildenafil v. Bosentan | 26 | Randomized, double-blind | IPAH, CTD | III | 16 wk | 55m | KCCQ | No significant difference in HRQoL scores between treatments by intent-to-treat. Significant difference between treatments by per-protocol analysis. |
| 2006 | (46) | Exercise training | 30 | Randomized, controlled | PAH, CTEPH | II, III, IV | 15 wk | 111m | SF-36 | Significant improvement in SF-36 PCS, MCS, as well as physical functioning, role-physical, social functioning, mental health, and vitality domains. |
| 2007 | (47) | Sitaxsentan | 42 | Post hoc analysis of RCT | CTD | II, III | 12 wk | 58m | SF-36 | Significant improvement in physical functioning and role-physical domains. |
Definition of abbreviations: 6MWD = six-minute walk distance; AA = anorexigen-associated pulmonary arterial hypertension; CHD = pulmonary arterial hypertension associated with congenital heart disease; CHQ = Chronic Heart Failure Questionnaire; CTD = pulmonary arterial hypertension associated with connective disuse disease; CTEPH = chronic thromboembolic pulmonary hypertension; EQ-5D = EuroQol; HIV = pulmonary arterial hypertension associated with human immunodeficiency virus; IPAH = idiopathic pulmonary arterial hypertension; KCCQ = Kansas City Cardiomyopathy Questionnaire; MLHFQ = Minnesota Living with Heart Failure Questionnaire; NHP = Nottingham Health Profile; NYHA = New York Heart Association; PAH = Pulmonary arterial hypertension; PCS = Physical Component Summary; RCT = randomized controlled trial; SF-36 = Medical Outcome Study 36-item Short Form Health Survey; VAS = visual analog score.