Mortality risk given per group as above (actual risk would be higher as includes hospitalisation) e Downgraded due to indirectness as composite outcome rather than protocol outcome Table 66: Ivabradine versus placebo (CKD class 3a/b) Outcomes No of Participant s (studies) Follow up Quality of the evidence (GRADE) Relative effect Anticipated absolute effects Risk with Placebo Risk difference with Ivabradine (95% CI) Renal function: change in eGFR LOWa due to risk of bias The mean eGFR in control was 53.7 ml/min (SD The mean eGFR in the intervention groups was (2 lower to 2.4 higher) Renal failure 1579 VERY LOWa,b due to risk of bias, imprecision (from 31 fewer to 29 more) VERY LOWa,b due to risk of bias, imprecision (from 24 fewer to 0 more) Bradycardia (symptomatic only) LOWa due to risk of bias (from 7 more to 65 more) a Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias b Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs Treating Heart Failure Chronic Heart Failure NICE 2018. All rights reserved. Subject to Notice of rights. ISBN: Table 67: MRA versus placebo (CKD class 3a/b) Outcomes No of Participants (studies) Follow up Quality of the evidence (GRADE) Relative effect Anticipated absolute effects Risk with placebo Risk difference with MRA (95% CI) All-cause mortality (RR) 792 LOWa,b,c due to risk of bias (subgroup), imprecision (from 66 fewer to 6 more) Combined outcome: cardiovascular mortality or HF admission (RR) VERY LOWa,c,d due to risk of bias, indirectness, imprecision (from 45 fewer to 145 fewer) HF hospitalisation (RR) 792 VERY LOWa,c,e due to risk of bias (subgroup), indirectness, imprecision (from 60 fewer to 10 more) Renal function change in eGFR 883 VERY LOWa,c due to risk of bias, imprecision The mean change in eGFR in the control groups was 4.15 ml/min (improvement) The mean change in eGFR in the intervention groups was 2.11 less improvement (4.23 less to 0.01 more) LOWa,f due to risk of bias (from 33 more to 260 more) a Downgraded by 1 increment if the majority of the evidence was at high risk of bias, and downgraded by 2 increments if the majority of the evidence was at very high risk of bias b Reports mortality as relative risk, rather than protocol time to event but not downgraded c Downgraded by 1 increment if the confidence interval crossed one MID or by 2 increments if the confidence interval crossed both MIDs d Downgraded 1 increment for indirectness as reporting compound outcome rather than numbers of hospitalisations e Downgraded 1 increment for indirectness as reporting only proportion having HF hospitalisations, not numbers of all cause hospitalisations f Statistical heterogeneity, but not downgraded as both studies appear to show clinically important difference (harm). 