| Reference | Study type | Population | Intervention and comparison | Outcomes | Risk of bias |
|---|---|---|---|---|---|
| «Filippatos G, Anker SD, Agarwal R, et al. Finereno...»1 | RCT NCT02540993 |
Randomized 1:1, double-blind, placebo-controlled trial. Median follow-up period: 2.6 years (interquartile range, 2.0-3.4 years). Between September 2015 and June 2018, 13 911 patients were screened and 5734 were randomized. 5674 were included in the full analysis set. Western Europe 21 %, Eastern Europe 24 %, North America 15.7 %, Asia 24.6 %, Latin America 11 %, Other 3.6 %. Included patients were ≥ 18 years with type 2 diabetes and urine albumin-to-creatinine ratio 30 to 5000 mg/g and an estimated glomerular filtration rate ≥ 25 to < 75 mL per min per 1.73 m2, treated with optimized renin-angiotensin system blockade. Serum potassium ≤ 4.8 mmol/l. 45.9 % of patients had CVD at baseline. Excluded patients had a non-diabetic kidney disease, uncontrolled hypertension, HbA1c > 12 %, SBP < 90 mmHg, history of heart failure with reduced ejection fraction or recent CV event, dialysis for acute kidney failure or kidney transplant. |
Intervention: Finerenone (BAY94-8862) Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy. Comparison: Placebo Participants received matching placebo once daily in addition to standard of care therapy. |
The composite cardiovascular outcome included time to cardiovascular death, myocardial
infarction, stroke, or hospitalization for heart failure. Prespecified cardiovascular analyses included analyses of the components of this composite and outcomes according to CVD history at baseline. |
Low |
| «Pitt B, Filippatos G, Agarwal R, et al. Cardiovasc...»2 | RCT NCT02545049 |
Randomized 1:1, double-blind, placebo-controlled trial. Median follow-up period: 3.4 years. Between September 2015 and October 2018, 19 381 patients were screened and 7437 were randomized. 7352 patients were included in the full analysis set. Western Europe 21 %, Eastern Europe 24 %, North America 15.7 %, Asia 24.6 %, Latin America 11 %, Other 3.6 %. Included patients were ≥ 18 years with type 2 diabetes and urine albumin-to-creatinine ratio of 30 to less than 300 and an estimated glomerular filtration rate (eGFR) of 25 to 90 ml per minute per 1.73 m2 of body-surface area (stage 2 to 4 CKD) or a urinary albumin-to-creatinine ratio of 300 to 5000 and an eGFR of at least 60 ml per minute per 1.73 m2 (stage 1 or 2 CKD), treated with optimized renin-angiotensin system blockade. Serum potassium ≤ 4.8 mmol/l. Excluded patients had a non-diabetic kidney disease, uncontrolled hypertension, HbA1c > 12 %, SBP < 90 mmHg, history of heart failure with reduced ejection fraction or recent CV event, dialysis for acute kidney failure or kidney transplant. |
Intervention: Finerenone (BAY94-8862) Participants received finerenone 10 mg or 20 mg once daily in addition to standard of care therapy. Comparison: Placebo Participants received matching placebo once daily in addition to standard of care therapy. |
The primary outcome, assessed in a time-to-event analysis, was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. | Low |
| «Agarwal R, Filippatos G, Pitt B, et al. Cardiovasc...»3 | pooled RCT | For this prespecified analysis, two phase III, multicentre, double-blind trials (FIDELIO
and FIGARO) involving patients with CKD and type 2 diabetes, randomized 1:1 to finerenone
or placebo, were combined. 13 026 patients with a median follow-up of 3.0 years (interquartile range 2.3–3.8 years). |
Same as above. | Same as above. | Low |
RCT=randomized controlled trial
| Reference | Comments |
|---|---|
| «Filippatos G, Anker SD, Agarwal R, et al. Finereno...»1 | The FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes with optimized renin-angiotensin system blockade. |
| «Pitt B, Filippatos G, Agarwal R, et al. Cardiovasc...»2 | The FIGARO-DKD trial (Finerenone in Reducing Cardiovascular Mortalityand Morbidity in Diabetic Kidney Disease), evaluatedwhether treatment with finerenone would lead to lower risks of cardiovascular events and death from cardiovascular causes among patients with either stage 2 to 4 CKD and moderately elevated albuminuria or stage 1 or 2 CKD and severely increased albuminuria — a patient population at high cardiovascular risk that was excluded from or understudied in the FIDELIO-DKD trial. |
| «Agarwal R, Filippatos G, Pitt B, et al. Cardiovasc...»3 | FIDELITY pooled analysis The complementary studies FIDELIO-DKD and FIGARO-DKD in patients with type 2 diabetes and chronic kidney disease (CKD) examined cardiovascular and kidney outcomes in different, overlapping stages of CKD. The purpose of the FIDELITY analysis was to perform an individual patient-level prespecified pooled efficacy and safety analysis across a broad spectrum of CKD to provide more robust estimates of safety and efficacy of finerenone compared with placebo. |
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Hazard ratio (95% CI) |
|---|---|---|---|---|---|
| «Filippatos G, Anker SD, Agarwal R, et al. Finereno...»1 | 5674 | 2.6 | 367/2833 (13 %) | 420/2841 (14.8 %) | 0.86 (0.75-0.99); P=0.034 |
| «Pitt B, Filippatos G, Agarwal R, et al. Cardiovasc...»2 | 7352 | 3.4 | 458/3686 (12.4 %) | 519/3666 (14.2 %) | 0.87 (0.76-0.98); p=0.03 |
| «Agarwal R, Filippatos G, Pitt B, et al. Cardiovasc...»3 | 13026 | 3.0 | 825/6519 (12.7 %) | 939/6507 (14.4 %) | 0.86 (0.78-0.95); p=0.0018 |
| Level of evidence: moderate Assess the risk of bias and delete irrelevant sources of bias: The quality of evidence is downgraded due to imprecision. |
|||||
I=intervention; C=comparison; CI=confidence interval
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| «Filippatos G, Anker SD, Agarwal R, et al. Finereno...»1 | 5674 | 2.6 | 128/2833 (4.5 %) | 150/2841 (5.3 %) | 0.86 (0.68-1.08) |
| «Pitt B, Filippatos G, Agarwal R, et al. Cardiovasc...»2 | 7352 | 3.4 | 194/3686 (5.3 %) | 214/3666 (5.8 %) | 0.90 (0.74-1.09) |
| «Agarwal R, Filippatos G, Pitt B, et al. Cardiovasc...»3 | 13026 | 3.0 | 322/6519 (4.9 %) | 364/6507 (5.6 %) | 0.88 (0.76-1.02); p=0.092 |
| Level of evidence: low Assess the risk of bias and delete irrelevant sources of bias: The quality of evidence is downgraded due to serious imprecision. |
|||||
I=intervention; C=comparison; CI=confidence interval
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| «Filippatos G, Anker SD, Agarwal R, et al. Finereno...»1 | 5674 | 2.6 | 70/2833 (2.5 %) | 87/2841 (3.1 %) | 0.80 (0.58-1.09) |
| «Pitt B, Filippatos G, Agarwal R, et al. Cardiovasc...»2 | 7352 | 3.4 | 103/3686 (2.8 %) | 102/3666 (2.8 %) | 0.99 (0.76-1.31) |
| «Agarwal R, Filippatos G, Pitt B, et al. Cardiovasc...»3 | 13026 | 3.0 | 173/6519 (2.7 %) | 189/6507 (2.9 %) | 0.91 (0.74-1.12); p=0.36 |
| Level of evidence: low Assess the risk of bias and delete irrelevant sources of bias: The quality of evidence is downgraded due to very serious imprecision. |
|||||
I=intervention; C=comparison; CI=confidence interval
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| «Filippatos G, Anker SD, Agarwal R, et al. Finereno...»1 | 5674 | 2.6 | 90/2833 (3.2 %) | 87/2841 (3.1 %) | 1.03 (0.76-1.38) |
| «Pitt B, Filippatos G, Agarwal R, et al. Cardiovasc...»2 | 7352 | 3.4 | 108/3686 (2.9 %) | 111/3666 (3.0 %) | 0.97 (0.74-1.26) |
| «Agarwal R, Filippatos G, Pitt B, et al. Cardiovasc...»3 | 13026 | 3.0 | 198/6519 (3.0 %) | 198/6507 (3.0 %) | 0.99 (0.82-1.21); p=0.95 |
| Level of evidence: low Assess the risk of bias and delete irrelevant sources of bias: The quality of evidence is downgraded due to very serious imprecision. |
|||||
I=intervention; C=comparison; CI=confidence interval
| Reference | Number of studies and number of patients (I/C) | Follow-up time | Absolute number of events (%) I | Absolute number of events (%) C | Relative effect (95% CI) |
|---|---|---|---|---|---|
| «Filippatos G, Anker SD, Agarwal R, et al. Finereno...»1 | 5674 | 2.6 | 139/2833 (4.9 %) | 162/2841 (5.7 %) | 0.86 (0.68-1.08) |
| «Pitt B, Filippatos G, Agarwal R, et al. Cardiovasc...»2 | 7352 | 3.4 | 117/3686 (3.2 %) | 163/3666 (4.4 %) | 0.71 (0.56-0.90) |
| «Agarwal R, Filippatos G, Pitt B, et al. Cardiovasc...»3 | 13026 | 3.0 | 256/6519 (3.9 %) | 325/6507 (5.0 %) | 0.78 (0.66-0.92); p=0.0030 |
| Level of evidence: moderate Assess the risk of bias and delete irrelevant sources of bias: The quality of evidence is downgraded due to inconsistency and imprecision. |
|||||
I=intervention; C=comparison; CI=confidence interval