Table 1.
Heart failure studies in general population with clinical characteristics including creatinine- or eGFR-based inclusion criterion
| Trial, yr | Age and Diabetes | < Creatinine (mean) or > GFR |
|---|---|---|
| Angiotensin-converting enzyme inhibitors | ||
| SAVE 1992 (53) | 59 yr, 29% | <2.5 mg/dl |
| SOLVD 1991 (54) | 61 yr, 26% | <2.5 mg/dl (1.2 mg/dl) |
| SOLVD prevent 1992 (55) | 59 yr, 15% | <2.5 mg/dl (1.2 mg/dl) |
| Angiotensin receptor blockers | ||
| CHARM 2003 (56) | 66 yr, 28% | <3 mg/dl |
| β-Blockers | ||
| CIBIS II 1999 (30) | 61 yr, 12% | <3.4 mg/dl |
| COPERNICUS 2001 (31) | 63 yr, 26% | <2.8 mg/dl (1.4 mg/dl) |
| MERIT HF 1999 (29) | 63 yr, 25% | — |
| SENIORS (32) | 76 yr, 27% | <2.8 mg/dl (1.15 mg/dl) |
| Mineralocorticoid receptor antagonists | ||
| RALES 1999 (57) | 65 yr, NA | <2.5 mg/dl |
| EMPHASIS-HF 2011 (58) | 69 yr, 34% | >30 ml/min (1.1 mg/dl) |
| EPHESUS 2003 (59) | 64 yr, 32% | <2.5 mg/dl (1.1 mg/dl) |
| Angiotensin receptor neprilysin inhibitors | ||
| PARADIGM HF 2014 (26). | 64 yr, 35% | >30 ml/min (1.1 mg/dl) |
| Ivabradine | ||
| SHIFT 2010 (60) | 61 yr, 30% | (74 ml/min per 1.73 m2) |
| Cardiac resynchronization therapy | ||
| RAFT 2010 (45) | 66 yr, 30% | 51% patients <60 ml/min per 1.73 m2 a |
| SGLT2 inhibitor | ||
| DAPA-HF 2019 (36) | 66 yr, 41% | >30 ml/min per 1.73 m2 |
| EMPEROR-reduced 2020 | 67 yr, 50% | >20 ml/min per 1.73 m2 |
The table includes pivotal studies that have helped us to draw our conclusions on therapy of patients with HFrEF and CKD (particularly stage 3). It highlights that patients included in these studies had relatively high creatinine and low eGFR, owing to the fact that CKD is common in patients with heart failure. Hence, significant numbers of patients with CKD were included. Studies included a significant proportion of patients with diabetes. SAVE, Survival and Ventricular Enlargement; SOLVD, Studies of Left Ventricular Dysfunction; CHARM, Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity; CIBIS II, Cardiac Insufficiency Bisoprolol Study II; COPERNICUS, Carvedilol Prospective Randomized Cumulative Survival; MERIT HF, Metoprolol CR/XL Randomized Intervention Trial in Congestive Heart Failure; SENIORS, Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure; RALES, Randomized Aldactone Evaluation Study; NA, not available; EMPHASIS-HF, Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure; EPHESUS, Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study; PARADIGM HF, Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure; SHIFT, Systolic Heart Failure Treatment with the IF inhibitor ivabradine trial; RAFT, Resynchronization–Defibrillation for Ambulatory Heart Failure Trial; DAPA-HF, Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure; EMPEROR reduced, EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction.
51% of the included patients had eGFR<60 ml/min per 1.73 m2.