Background
Objectives
Methods
Eligibility criteria
Literature search
Study selection
Data collection and analysis
Risk of bias
Statistical analysis
Results
Trial selection
Trial characteristics
Author | Year | Population | Exp (N) | Cont (N) | Intervention | Drug dose | Follow-up (months) |
---|---|---|---|---|---|---|---|
Akbulut | 2003 | HFrEF, EF ≤ 35%, NYHA III | 35 | 35 | spironolactone | 25 mg daily | 3 |
Boccanelli | 2009 | HFrEF, EF ≤ 45%, NYHA II | 215 | 223 | canrenone | 25 mg daily | 12 |
Chan | 2007 | HFrEF, EF < 40%, NYHA I–III | 23 | 25 | spironolactone | 25 mg daily | 12 |
Cicoira | 2002 | HFrEF, EF ≤ 45%, NYHA III | 54 | 52 | spironolactone | 25 mg daily | 12 |
Deswal | 2011 | HFpEF, EF ≥ 50%, NYHA II–III | 25 | 23 | eplerenone | 25 mg daily | 6 |
Edelmann | 2013 | HFpEF, EF ≥ 50%, NYHA II–III | 213 | 209 | spironolactone | 25 mg daily | 12 |
Edwards | 2009 | HFpEF, CKD stage 2–3 | 56 | 56 | spironolactone | 25 mg daily | 9 |
Zannad | 2011 | HFrEF, EF ≤ 35%, NYHA II | 1364 | 1373 | eplerenone | 25–50 mg daily | 21 |
Pitt | 2003 | MI + HFrEF, EF ≤ 40% | 3319 | 3313 | eplerenone | 25–50 mg daily | 16 |
Gao | 2007 | HFrEF, EF < 45%, NYHA II–IV | 58 | 58 | spironolactone | 20 mg daily | 6 |
Pitt | 2013 | HFrEF, EF ≤ 40%, CKD stage 2–3 | 63 | 65 | spironolactone | 25–50 mg daily | 1 |
Pitt | 1999 | HFrEF, EF < 35%, NYHA III–IV | 822 | 841 | spironolactone | 25–50 mg daily | 24 |
Pitt | 2014 | HFpEF, EF ≥ 45% | 1722 | 1723 | spironolactone | 15–45 mg daily | 40 |
Udelson | 2010 | HFrEF, EF ≤ 35% NYHA II–III | 117 | 109 | eplerenone | 50 mg daily | 9 |
Vizzardi | 2014 | HFrEF, EF < 40%, NYHA I–II | 65 | 65 | spironolactone | 25–100 mg daily | 44 |
Risk of bias within included trials
Author | Year | Allocation concealment | Blinding | Intention to treat analysis | Loss to follow-up (%) | Early trial termination |
---|---|---|---|---|---|---|
Akbulut | 2003 | Unclear | No | Yes | 0.0 | No |
Boccanelli | 2009 | Yes | Yes | Yes | 6.2 | No |
Chan | 2007 | Unclear | Yes | Yes | 0.0 | No |
Cicoira | 2002 | Unclear | Yes | Yes | 6.6 | No |
Deswal | 2011 | Yes | Yes | No | 4.3 | No |
Edelmann | 2013 | Yes | Yes | Yes | 1.2 | No |
Edwards | 2009 | Unclear | Yes | No | 2.7 | No |
Zannad | 2011 | Yes | Yes | Yes | 1.2 | Yes |
Pitt | 2003 | Yes | Yes | Yes | 0.3 | No |
Gao | 2007 | Yes | Yes | Yes | 0.0 | No |
Pitt | 2013 | No (open label Aldactone) | Yes | Yes | 0.0 | No |
Pitt | 1999 | Yes | Yes | Yes | 0.0 | Yes |
Pitt | 2014 | Yes | Yes | Yes | 3.8 | No |
Udelson | 2010 | Yes | Yes | Yes | 0.0 | No |
Vizzardi | 2014 | Yes | No | Yes | 0.0 | No |
Results of meta-analysis
Outcome | № of participants (studies) | Quality of the evidence (GRADE) | Relative effect (95% CI) | Anticipated absolute effects | |
---|---|---|---|---|---|
Risk with placebo | Risk difference with MRA | ||||
Cardiovascular death | 15115 (7 RCTs) | ⨁⨁⨁ MODERATEa | RR 0.81 (0.75 to 0.87) | 155 per 1000 | 29 fewer per 1000 (39 fewer to 20 fewer) |
Cardiovascular death - rEF | 11670 (6 RCTs) | ⨁⨁⨁⨁ HIGH | RR 0.79 (0.73 to 0.86) | 171 per 1000 | 36 fewer per 1000 (46 fewer to 24 fewer) |
Cardiovascular death - pEF | 3445 (1 RCT) | ⨁⨁⨁ MODERATEb | RR 0.91 (0.74 to 1.11) | 102 per 1000 | 9 fewer per 1000 (27 fewer to 11 more) |
All cause mortality | 15919 (12 RCTs) | ⨁⨁⨁ MODERATEc | RR 0.83 (0.77 to 0.88) | 182 per 1000 | 31 fewer per 1000 (42 fewer to 22 fewer) |
All cause mortality - rEF | 11892 (8 RCTs) | ⨁⨁⨁⨁ HIGH | RR 0.81 (0.75 to 0.87) | 197 per 1000 | 38 fewer per 1000 (49 fewer to 26 fewer) |
All cause mortality - pEF | 4027 (4 RCTs) | ⨁⨁⨁ MODERATEd | RR 0.92 (0.79 to 1.08) | 136 per 1000 | 11 fewer per 1000 (29 fewer to 11 more) |
Cardiac hospitalization | 15669 (10 RCTs) | ⨁⨁⨁ MODERATEd | RR 0.80 (0.70 to 0.92) | 217 per 1000 | 43 fewer per 1000 (65 fewer to 17 fewer) |
Cardiac hospitalization - rEF | 11754 (7 RCTs) | ⨁⨁⨁ MODERATEd | RR 0.76 (0.64 to 0.90) | 245 per 1000 | 59 fewer per 1000 (88 fewer to 24 fewer) |
Cardiac hospitalization - pEF | 3915 (3 RCTs) | ⨁⨁⨁ MODERATEd | RR 0.91 (0.67 to 1.24) | 134 per 1000 | 12 fewer per 1000 (44 fewer to 32 more) |
Hyperkalemia | 16321 (15 RCTs) | ⨁⨁⨁⨁ HIGH | RR 2.03 (1.78 to 2.31) | 37 per 1000 | 39 more per 1000 (29 more to 49 more) |
Gynecomastia or breast pain - nonselective | 6432 (8 RCTs) | ⨁⨁⨁⨁ HIGH | RR 7.37 (4.42 to 12.30) | 5 per 1000 | 30 more per 1000 (16 more to 53 more) |
Gynecomastia or breast pain - selective | 9417 (3 RCTs) | ⨁⨁⨁⨁ HIGH | RR 0.74 (0.43 to 1.27) | 7 per 1000 | 2 fewer per 1000 (4 fewer to 2 more) |