Table 2. Summary of randomized controlled trials of PDE-5 inhibitors and guanylyl cyclase agonists in patients with PH-LHD.
| Study name | Drug/author/year | Patients | Primary endpoint | Results |
|---|---|---|---|---|
| Sil-HF, NCT01616381 (33) | Sildenafil/Stavanger/2012 | HFrEF, 120 | Patient global assessment; 6-minute walk test at baseline, 8 and 24 weeks | Ongoing study |
| ULTIMATE-SHF, NCT01646515 (34) | Udenafil/Kim/2012 | HFrEF, 41 | VO2max with cardiopulmonary exercise test | Not reported |
| RELAX, NCT00763867 (32) | Sildenafil/Redfield/2013 | HFpEF, 216 | Change in peak oxygen consumption after 24 weeks of therapy | No statistically significant difference between treatment and placebo groups |
| PITCH-HF, NCT01910389 (35) | Tadalafil/Semigram/2013 | HFrEF, 23 | Composite outcome of CV mortality or HF hospitalization | Not reported |
| Sildenafil/Fernandes/2015 (36) | HFrEF, 35 | RV function, measured by CMR | No statistically significant change in parameters; no improvement in left ventricular parameters or in the fractional area change of the pulmonary artery | |
| LEPHT (37) | Riociguat/Bonderman/2013 | HFrEF, 201 | Placebo-corrected change from baseline at week 16 in mPAP | Primary endpoint not met; secondary endpoints: increase in cardiac index, decrease in PVR and SVR |
| DILATE-1 (38) | Riociguat/Bonderman/2014 | HFpEF, 36 | mPAP at rest | Primary endpoint not met; secondary endpoints: increased stroke volume, decreased systolic blood pressure and right ventricular end-diastolic area |
| DYNAMIC, NCT02744339 (39) | Riociguat/Bonderman/2016 | HFpEF, 114 | Change from baseline of cardiac output at rest, measured by right heart catheterization after 26 weeks of study drug treatment | Ongoing study |
PH-LHD, pulmonary hypertension-left heart disease; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; mPAP, mean pulmonary arterial pressure; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; CMR, cardiovascular magnetic resonance; CV, cardiovascular.