Introduction
Dilemma in diagnosing HFpEF
Current understanding of pathophysiological mechanisms in HFpEF
Treatment of HFpEF
Focus on comorbidities
Dilemmas in past HFpEF trials
Conventional HF drugs in HFpEF
ACE inhibitors and AT1 antagonists
Mineralocorticoid receptor antagonists
Beta-blockers
Angiotensin receptor neprilysin inhibitor
Ivabradine
Cardiac glycosides
New options in treatment of HFpEF
Study name | Intervention | Study size | Primary endpoint | Identifier |
---|---|---|---|---|
Sodium glucose cotransporter-2 inhibitors | ||||
EMPEROR-PRESERVED | Empagliflozin | 4126 | Change in CV death rate, time-to-first HF hospitalization | NCT03057951 |
DELIVER | Dapagliflozin | 4700 | Change in CV death rate, time-to-first HF hospitalization/first urgent HF visit | NCT03619213 |
SOLOIST | Sotagliflozin | 4000 | Change in CV death rate, time-to-first HF hospitalization | NCT03521934 |
Mineralocorticoid receptor antagonists | ||||
SPIRRIT | Spironolactone | 3500 | Change in overall death rate | NCT02901184 |
SPIRIT-HF | Spironolactone | 1300 | Change in CV death rate, number of recurrent HF hospitalizations | 2017-000697-11 |
Device therapy | ||||
GUIDE-HF | CardioMEMS | 3600 | Change in all-cause mortality, total number of HF hospitalizations, iv diuretic visits | NCT03387813 |
REDUCE LAP-HF TRIAL II | IASD System II | 608 | Change in incidence of and time-to-CV mortality or first non-fatal, ischemic stroke, total rate per patient year of HF admissions or healthcare facility visits for IV diuresis for HF and time-to-first HF event, KCCQ | NCT03088033 |
Study name | Intervention | Study size | Primary endpoint | Identifier |
---|---|---|---|---|
Soluble guanylyl cyclase stimulators and activators | ||||
SERENADE | Macitentan | 300 | Change in NT-proBNP levels | NCT03153111 |
VITALITY | Vericiguat | 735 | Change in QOL | NCT03547583 |
Inorganic nitrates/nitrites | ||||
PMED | Oral nitrate | 120 | Change in nitrate/nitrite level, microbiome | NCT02980068 |
Angiotensin receptor neprilysin inhibitor | ||||
PERSPECTIVE | LCZ696 | 520 | Change in cognitive function | NCT02884206 |
PARALLAX | LCZ696 | 2500 | Change in NT-proBNP levels | NCT03066804 |
Sodium glucose cotransporter-2 inhibitors | ||||
PRESERVED-HF | Dapagliflozin | 320 | Change in NT-proBNP levels | NCT03030235 |
ERADICATE-HF | Ertugliflozin | 36 | Change in proximal sodium reabsorption | NCT03416270 |
Restoring mitochondrial energy | ||||
Elamipretide in patients hospitalized with congestion due to HF | Elamipretide | 300 | Change in NT-pro-BNP levels | NCT02914665 |
Device therapy | ||||
CCM-HFpEF | CCM | 50 | Change in QOL | NCT03240237 |
Study name | Intervention | Study size | Primary endpoint | Identifier |
---|---|---|---|---|
Soluble guanylyl cyclase stimulators and activators | ||||
CAPACITY-HF | IW 1973 | 184 | Change in peak VO2 | NCT03254485 |
DYNAMIC | Riociguat | 114 | Change in CO | NCT02744339 |
Phosphodiesterase-5 inhibitors | ||||
Sildenafil in HFPEF and PH | Sildenafil | 52 | Change in PAP, CO | 2010-020153-14 |
Inorganic nitrates/nitrites | ||||
INABLE | Oral inorganic nitrite | 100 | Change in peak VO2 | NCT0271312 |
KNO3CK OUT HFPEF | Oral potassium nitrate | 76 | Change in QOL, muscle blood flow, SVR reserve | NCT0284079 |
PH-HFPEF | Oral nitrite | 26 | Change in PAP at exercise | NCT03015402 |
ONOH | Oral nitrite | 18 | Change in peak VO2 | NCT02918552 |
Neo40 | Oral nitrate supplement | 25 | Change in exercise capacity, E/e′, RVSP | NCT03289481 |
3AR-selective agonists | ||||
BETA3_LVH | Mirabegron | 297 | Change in LVMI, E/e′ | NCT02599480 |
SPHERE-HF | Mirabegron | 80 | Change in PVR | NCT02775539 |
Sodium glucose cotransporter-2 inhibitors | ||||
EMPERIAL-PRESERVED | Empagliflozin | 300 | Change in 6MWD | NCT03448406 |
Other antidiabetic drugs | ||||
Metformin for PH + HFPEF | Metformin | 32 | Change in PAP at exercise | NCT03629340 |
cGETS | Sitagliptin | 25 | Change in hemodynamics during Dobutamine stress test, diastolic dysfunction, LV hypertrophy | 2012-002877-71 |
Pirfenidone | ||||
PIROUETTE | Pirfenidone | 200 | Change in ECV | NCT02932566 |
Cell therapy | ||||
CELL-pEF | CD34+ cell therapy | 30 | Change in E/e′ | NCT02923609 |
Restoring mitochondrial energy | ||||
Elamipretide in subjects with stable HFpEF | Elamipretide | 46 | Change in E/e′ | NCT02814097 |
FAIR-HFpEF | Ferric carboxymaltose | 200 Change in 6MWD | NCT03074591 | |
PREFER-HF | Ferric carboxymaltose | 72 | Change in 6MWD | NCT03833336 |
Targeting intracellular Ca2+ sensitivity | ||||
HELP | Levosimendan | 36 | Change in PCWP at exercise | NCT03541603 |
Prostaglandin derivatives | ||||
ILO-HOPE | Iloprost | 34 | Change in PCWP after exercise | NCT03620526 |
SOUTHPAW | Treprostinil | 310 | Change in 6MWD | NCT03037580 |
Device therapy | ||||
RAPID-HF | CRT | 30 | Change in VO2 at VAT | NCT02145351 |
PREFECTUS | CRT | 10 | Change in systolic and diastolic reserve index | NCT03338374 |