Table 3: Summary of Clinical Trials of Pulmonary Hypertension-specific Therapy in Heart Failure with Reduced Ejection Fraction.
| Study | Drug | Type | n | Inclusion Criteria | Outcome | Conclusion |
|---|---|---|---|---|---|---|
| FIRST[50] | Epoprostenol IV | Multicentre randomised controlled trial | 471 | NYHA class IIIB/IV, no specific requirement for PH | Mortality | Terminated early due to mortality in treatment arm |
| HEAT[51] | Darusentan | Single-centre randomised controlled trial | 179 | NYHA class III, no specific requirement for PH | Change in cardiac index and PAWP after 3 weeks of treatment | Improvement in cardiac output with no change in pulmonary artery pressures |
| EARTH[52] | Darusentan | Multicentre randomised controlled trial | 642 | NYHA class IIIB/IV, no specific requirement for PH | Change in LV size on cardiac MRI after 24 weeks of treatment | No benefit |
| REACH-1[49] | Bosentan (500 mg twice a day) | Multicentre randomised controlled trial | 370 aim, 174 recruited total | NYHA class III/IV, no specific requirement for PH | Change in HF symptoms after 26 weeks of treatment | Early termination, although trend to benefit in those that completed study |
| Guazzi et al.[54] | Sildenafil | Multicentre randomised controlled trial | 46 | NYHA class II/III, no specific requirement for PH | Change in VO2 max after 6 months of treatment | Improved exercise capacity |
| LEPHT[56] | Riociguat | Multicentre randomised controlled trial | 201 | LVEF ≤40%, mPAP ≥25 mmHg by right heart catheterisation | Change in mPAP | No benefit |
| PITCH-HF (NCT01910389) | Tadalafil | Multicentre randomised controlled trial | 23 | NYHA class II/III, documented PH within 6 months | Mortality and HF hospitalisations after up to 3 years of treatment | Terminated due to poor enrolment |
| SIL-HF (NCT01616381) | Sildenafil | Two-arm randomised controlled pilot study | 75 | NYHA class II/III, secondary PH >40 mmHg on TTE | Change in patient- reported symptoms and 6-minute walk test after 6 months of treatment | Enrolment complete, results pending |
HF = heart failure; LV = left ventricular; LVEF = left ventricular ejection fraction; mPAP = mean pulmonary artery pressure; NYHA = New York Heart Association; PAWP = pulmonary artery wedge pressure; PH = pulmonary hypertension; TTE = trans-thoracic echocardiography.