Sacubitril/valsartan compared with control for heart failure with reduced ejection fraction | |||||

Patient or population: heart failure with reduced ejection fraction Intervention: sacubitril/valsartan Comparison: control | |||||

Outcomes | No of participants (studies) follow-up | Certainty of the evidence (GRADE) | Relative effect (95% CI) | Anticipated absolute effects | |

Risk with control | Risk difference with ARNI | ||||

All-cause mortality follow-up: mean 23 months | 10 794 (seven RCTs) | ⨁⨁⨁◯ MODERATE* | RR 0.86(0.79 to 0.94) | 161 per 1.000 | 23 fewer per 1.000(34 fewer to 10 fewer) |

Serious adverse events follow-up: mean 23 months | 10 794 (seven RCTs) | ⨁⨁⨁◯ MODERATE* | RR 0.89(0.86 to 0.94) | 418 per 1.000 | 46 fewer per 1.000(59 fewer to 25 fewer) |

Myocardial infarction follow-up: mean 25 months | 9051 (two RCTs) | ⨁◯◯◯ VERY LOW*†‡ | RR 0.98(0.71 to 1.35) | 16 per 1.000 | 0 fewer per 1.000(5 fewer to six more) |

Quality of life assessed with: MLHFQ follow-up: mean 2 months | 232 (two RCTs) | ⨁◯◯◯ VERY LOW§¶ | – | MD 5.19 score lower(8.37 lower to 2.01 lower) | |

Non-serious adverse events follow-up: mean 23 | 10 401 (nine RCTs) | ⨁⨁◯◯ LOW*† | RR 0.95(0.84 to 1.08) | 547 per 1.000 | 27 fewer per 1.000(88 fewer to 44 more) |

Rehospitalisations follow-up: mean 25 months | 9476 (four RCTs) | ⨁⨁◯◯ LOW*‡ | RR 0.77(0.69 to 0.87) | 159 per 1.000 | 37 fewer per 1.000(49 fewer to 21 fewer) |

The risk in the intervention group (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

GRADE, Working Group grades of evidence.

High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.

Moderate certainty: We are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.

Low certainty: Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect.

Very low certainty: We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect.

*Downgraded 1 for risk of bias, due to industry funding.

†Downgraded 1 for risk of inconsistency due to moderate heterogeneity.

‡Downgraded 1 for imprecision due to Trial Sequential Analysis showing that there was not enough information to confirm or reject a RRR of 15%. Moreover, the meta-analysis showed wide CI.

§Downgraded 2 for risk of bias.

¶Downgraded 2 for risk of inconsistency due to substantial heterogeneity.

RR, risk ratio; MD, mean difference; ARNI, angiotensin receptor blocker neprilysin inhibitor; RCTs, randomised controlled trials; MLHFQ, Minnesota Living with Heart Failure Questionnaire; MD, mean difference.