Table 3.
Summary of significant RCTs in addressing HFpEF and/or surrogates of HFpEF in patients with CKD and/or treated with dialysis
| Trial [reference] | Population | N | Intervention | Duration | Primary outcome(s) | Comments |
|---|---|---|---|---|---|---|
| I-PRESERVE [104] | HF and LVEF ≥45% and creatinine <221 µmol/L | 4128 | Irbesartan 300 mg or placebo | Mean 49.5 months | Death and cardiovascular hospitalization | No improvement in primary outcome with irbesartan |
| TOPCAT [105] | HF and LVEF ≥45% and eGFR >30 mL/min/1.73 m2 | 3445 | Spironolactone 15–45 mg or placebo | Mean 3.3 years | Cardiovascular death and HF hospitalization | No difference in primary outcome between groups |
| PARAGON-HF [107] | HF and LVEF ≥ 45% and eGFR > 30 mL/min/1.73 m2 | 4822 | Sacubitril–valsartan or valsartan | Median 35 months | Cardiovascular death and HF hospitalization | No difference in primary outcome between groups |
| SOLOIST [109] | Patients with type 2 DM recently hospitalized with HF and eGFR >30 mL/min/1.73 m2 | 1222 | Sotagliflozin 200–400 mg or placebo | Median 9.0 months | Cardiovascular death and HF hospitalization | Significant benefit [HR 0.69 (95% CI 0.52–0.85)] with sotagliflozin. Benefit in subgroup LVEF ≥50% [HR 0.48 (95% CI 0.27–0.86)] |
| EMPEROR-Preserved [110] | Symptomatic HF and LVEF ≥40% and eGFR >20 mL/min/1.73 m2 | 5988 | Empagliflozin 10 mg or placebo | Median 26.2 months | Cardiovascular death and HF hospitalization | Significant benefit with empagliflozin [HR 0.79 (95% CI 0.69–0.90)] |
| EMPULSE [111] | HF regardless of LVEF and eGFR >20 mL/min/1.73 m2 | 530 | Empagliflozin 10 mg or placebo | 90 days | Clinical benefit, composite of death, HF events and QoL | Empagliflozin clinical benefit compared with placebo-stratified win ratio [1.36 (95% CI 1.09–1.68)] |
| SPIRO-CKD [137] | Non-diabetic CKD eGFR 30–89 mL/min/1.73 m2 | 154 | Spironolactone 25 mg or chlorthalidone 25 mg | 40 weeks | LVM on CMR | No difference in LVM between groups |
| CREDENCE [129] | Diabetes and eGFR 30–89 mL/min/1.73 m2 and albuminuria | 4401 | Canagliflozin 100 mg or placebo | Median 2.62 years | ESKD, doubling creatinine, death from renal or CV causes | Reduction in primary outcome with canagliflozin [HR 0.70 (95% CI 0.59–0.82)] HF hospitalization [HR 0.61 (95% CI 0.47–0.80)] |
| DAPA-CKD [130] | CKD eGFR 25–75 mL/min/1.73 m2 and albuminuria | 4304 | Dapagliflozin 10 mg or placebo | Median 2.4 years | ESKD, decline in eGFR ≥50%, death from renal or CV causes | Reduction in primary outcome with dapagliflozin [HR 0.61 (95% CI 0.51–0.72)], HF hospitalization [HR 0.51 (95% CI 0.34–0.76)] |
| SPIN-DIAL [115, 116] | Patients on HD | 129 | Spironolactone (12.5–50 mg) or placebo | 36 weeks | Assess safety and tolerability of intervention | No difference in diastolic function on echocardiography between groups |
| Hammer et al. [115] | Patients on HD | 97 | Spironolactone 50 mg or placebo | 40 weeks | LVMI on CMRI | No difference in LVMI between groups |
| PIVOTAL [118] | Patients on HD >3 months and treated with ESA | 2141 | Proactive or reactive intravenous iron | Median 2.1 years | Death, myocardial infarction, stroke, HF hospitalisation | Proactive iron fewer primary end point events that reactive iron. Significant reduction in HF events with proactive iron [HR 0.66 (95% CI 0.46–0.94)] |
| PRIMO [121] | CKD, mild-moderate LVH, LVEF ≥50%, eGFR 15–60 mL/min/1.73 m2 | 227 | Paricalcitol or no therapy | 48 weeks | LVMI on CMRI | No difference in LVMI between groups |
| EVOLVE [122] | Patients on HD with hyperparathyroidism | 3883 | Cinacalcet or placebo | Mean 21.2 months | Death or cardiovascular event | No difference in primary outcome between groups. Fewer non-atherosclerotic CV events (including HF, sudden death) with cinacalcet [HR 0.84 (95% CI 0.74–0.96)] |
| Dörr et al. [124] | Patients on HD with hyperparathyroidism and LVH | 62 | Intravenous etelcalcetide or alfacalcidol | 12 months | LVMI on CMRI | Significantly less progression LVMI with etelcalcetide |
| Odudu et al. [132] | Patients on HD | 73 | Dialysate 37°C or 0.5°C below body temperature | 12 months | LVEF at CMRI | No change in primary endpoint but decreased LVMI with cool dialysis |
| FHN [131] | Patients on HD | 245 | Six times HD/week versus three times HD/week | 12 months | Composite of mortality, QoL and LV mass | Decreased LV mass with frequent HD |
CV: cardiovascular; DM: diabetes mellitus; ESKD: end-stage kidney disease; QoL: quality of life.