Table 2: Summary of Clinical Trials of Pulmonary Hypertension-specific Therapy in Heart Failure with Preserved Ejection Fraction.
| Study | Drug Studied | Study Type | n | Inclusion Criteria | Outcome | Conclusion |
|---|---|---|---|---|---|---|
| RELAX[40] | Sildenafil | Multicentre randomised controlled trial | 216 | Clinical diagnosis of HF, LVEF >50%, stable medical therapy | Change in VO2 max after 24 weeks of treatment | No benefit |
| Guazzi et al.[42] | Sildenafil | Single-centre randomised controlled trial | 44 | Clinical diagnosis of HF, sinus rhythm and no hospitalisation in the 6 months prior, LVEF ≥50%, sPAP >40 mmHg on TTE | Change in mean PAP after 12 months of treatment | Improvement in all parameters |
| DILATE-1[44] | Riociguat | Single-centre randomised controlled trial | 21 | Clinical diagnosis of HF, LVEF >50% and diastolic dysfunction on TTE | Change in mean PAP 6 hours post drug administration | No benefit |
| Hoendermis et al.[41] | Sildenafil | Single-centre randomised controlled trial | 52 | NYHA class II–IV, LVEF >45%, PAP >25 mmHg + PAWP >15 mmHg on RHC | Change in mean PAP after 12 weeks of treatment | No benefit |
| Simon et al.[47] | Inhaled inorganic nitrates | Single-centre phase II study | 36; 10 with HFpEF | Safety study, patients with PH were enrolled | Acute change in haemodynamics on RHC | Reduction in PCWP and mPAP |
| BADDHY[45] | Bosentan | Single-centre randomised controlled trial | 20 | 6MWT 150–450 m, LVEF >50%, PAP >25 mmHg + PCWP >15 mmHg on RHC | Change in 6-minute walk test after 12 and 24 weeks of treatment | Terminated early due to interim analysis that favoured the placebo |
| MELODY-1[46] | Macitentan | Multicentre placebo- controlled randomised phase II study | 63 | LVEF >30%, NYHA class II/III, CpcPH by right heart catheterisation | Safety (fluid retention or worsening NYHA class) | Increased fluid retention in study arm |
CpcPH = combined post- and pre-capillary pulmonary hypertension; HF = heart failure; HFpEF = heart failure with preserved ejection fraction; LVEF = left ventricular ejection fraction; mPAP = mean pulmonary artery pressure; NYHA = New York Heart Association; PAP = pulmonary artery pressure; PAWP = pulmonary artery wedge pressure; PCWP = pulmonary capillary wedge pressure; PH = pulmonary hypertension; sPAP = systolic pulmonary artery pressure; RHC = right heart catheterisation; TTE = trans-thoracic echocardiography.