Table 1.
Summary of Phase III Clinical Trials Conducted in the HFpEF Population and Subanalysis in the CKD Population
| Therapeutic Agent and Clinical Trial | Main Results | CKD Population in the Trial and Prespecified Results | Role in CKD |
|---|---|---|---|
|
CHARM-Preserved59 ARB: candesartan |
CV death and hospitalization for HF (HR 0.89; 95% CI, 0.77-1.03; P = 0.12); HF hospitalization (HR 0.84; 95% CI 0.70-1.00); P = 0.047 | <30% in both groups had eGFR < 60 mL/min/1.73 m2 No outcome results based on CKD |
Well known and established role of ARB in proteinuric CKD |
|
PARAGON-HF61 ARNI: sacubitril–valsartan |
CV death and hospitalization for HF (HR 0.87; 95% CI, 0.75-1.01; P = 0.06); 15% reduction in hospitalization for heart failure and 45% improvement in NYHA class | Mean eGFR in 2 groups 63 ± 19 and 62 ± 19 mL/min/1.73 m2; prespecified primary outcome by CKD: <60 mL/min/1.73 m2: HR 0.79 (0.66-0.95); ≥60 mL/min/1.73 m2: HR 1.01 (0.8-1.27); renal composite endpoint reduced by 50% compared with ARB in CKD subgroup (eGFR: 30-60 mL/min/1.73 m2) | No evaluation of ARNI in primary CKD |
|
TOPCAT75 MRA: spironolactone |
CV death and hospitalization for HF (HR 0.89; 95% CI, 0.77-1.04; P = 0.14); HF hospitalization (HR 0.83; 95% CI 0.69-0.99); P = 0.04 | 39% in both groups had eGFR < 60 mL/min/1.73 m2; prespecified primary outcome by CKD: <60 mL/min/1.73 m2: HR 0.95 (0.77-1.17); ≥60 mL/min/1.73 m2: HR 0.82 (0.66-1.02) | Role of novel nonsteroidal MRA is established in proteinuric diabetic kidney disease77 |
|
EMPEROR-Preserved67 SGLT2i: empagliflozin |
CV death and hospitalization for HF (HR 0.79; 95% CI, 0.69-0.9; P < 0.001); HF hospitalization (HR 0.73; 95% CI 0.61-0.88; P < 0.001) | 50% in both groups had eGFR < 60 mL/min/1.73 m2; prespecified primary outcome by CKD: <60 mL/min/1.73 m2: HR 0.78 (0.66-0.91); ≥60 mL/min/1.73 m2: HR 0.81 (0.65-1.00) | Well established role of empagliflozin in proteinuric and non proteinuric CKD with or without diabetes64 |
|
DELIVER68 SGLT2i: dapagliflozin |
CV death and hospitalization for HF (HR 0.82; 95% CI, 0.73-0.92; P < 0.001); worsening HF (HR 0.79; 95% CI, 0.69-0.91; P < 0.001). | Mean eGFR in 2 groups 63 ± 19 and 62±19 mL/min/1.73 m2; prespecified primary outcome by CKD: <60 mL/min/1.73 m2: HR 0.81 (0.69-0.94); ≥60 mL/min/1.73 m2: HR 0.84 (0.7-1.00) | Well established role of dapagliflozin in proteinuric CKD with or without diabetes66 |
CKD, chronic kidney disease; CI, confidence interval; CV, cardiovascular; eGFR, estimated glomerular filtration rate; HF, heart failure; MRA, mineralocorticoid-receptor antagonists; SGLT2i, sodium–glucose cotransporter 2 inhibitors; ARNI, angiotensin receptor–neprilysin inhibitor; ARB, angiotensin receptor blocker.