Beta‐blockers compared to placebo or no treatment for chronic heart failure with preserved ejection fraction

Patient or population: chronic heart failure with preserved ejection fraction
Setting: secondary care
Intervention: beta‐blockers
Comparison: placebo/no treatment

Cardiovascular mortality (RR)
follow‐up: range 21 months to 3.2 years

RR 0.78
(0.62 to 0.99)

1046
(3 RCTs)

⊕⊕⊝⊝
LOW ^{1 2}

Three additional studies (ELANDD; SWEDIC; Takeda 2004) reported that no deaths occurred

Heart failure hospitalisation (RR)
follow‐up: range 6 months to 3.2 years

RR 0.73
(0.47 to 1.13)

449
(4 RCTs)

⊕⊝⊝⊝
VERY LOW ^{1 3 4}

Follow‐up unclear for SWEDIC. ELANDD reported that no hospitalisation due to heart failure occurred

Hyperkalaemia

245 (1 RCT)

⊕⊝⊝⊝
VERY LOW^{1 7}

J‐DHF reported one participant in the intervention group (N = 120) experienced hyperkalaemia but did not report on this outcome for the control group. No further data were available from any of the other studies.

All‐cause mortality (RR)
follow‐up: range 21 months to 3.2 years

RR 0.82
(0.67 to 1.00)

1105
(4 RCTs)

⊕⊕⊝⊝
LOW ^{1 2}

Follow‐up unclear for Adamyan 2010. ELANDD, SWEDIC and Takeda 2004 reported that no deaths occurred

Quality of life (Minnesota)
Scale from: 0 to 105
follow‐up: mean 6 months

‐

93
(1 RCT)

⊕⊝⊝⊝
VERY LOW ^{5 6}

Lower = better, 5 point difference considered to be clinically meaningful

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

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

MRA compared to placebo or no treatment for chronic heart failure with preserved ejection fraction

Patient or population: chronic heart failure with preserved ejection fraction
Setting: secondary care
Intervention: MRA
Comparison: placebo/no treatment

Cardiovascular mortality (RR)
follow‐up: range 12 months to 3.3 years

RR 0.90
(0.74 to 1.11)

4070
(3 RCTs)

⊕⊕⊕⊝
MODERATE ¹

Two additional trials (RAAM‐PEF, Kurrelmeyer 2014) reported that no deaths occurred

Heart failure hospitalisation (RR)
follow‐up: range 24 weeks to 3.3 years

RR 0.82
(0.69 to 0.98)

3714
(3 RCTs)

⊕⊕⊕⊝
MODERATE ¹

Three additional trials (ALDO‐DHF ,Kurrelmeyer 2014, Upadhya 2017) reported that no hospitalisation due to heart failure occurred

Hyperkalaemia
follow‐up: range 24 weeks to 3.3 years

RR 2.11
(1.77 to 2.52)

4291
(6 RCTs)

⊕⊕⊕⊕
HIGH

Two trials defined hyperkalaemia ≥ 5.5 mEg/L

All‐cause mortality
follow‐up: range 9 months to 3.3 years

RR 0.91
(0.78 to 1.06)

4207
(5 RCTs)

⊕⊕⊕⊝
MODERATE ¹

Two additional trials (RAAM‐PEF, Kurrelmeyer 2014) reported that no deaths occurred

Quality of life (Minnesota)
Scale from: 0 to 105
follow‐up: range 9 months to 12 months

‐

511
(3 RCTs)

⊕⊕⊝⊝
LOW ^{2 3}

Lower = better, 5 points are considered a clinically significant difference

We did not pre‐specify which QoL scale was to be reported in the 'Summary of findings' table. To aid comparisons among 'Summary of findings' tables we chose to include the Minnesota Living with Heart Failure questionnaire and not the SMD across two scales

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

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

ACEI compared to placebo or no treatment for chronic heart failure with preserved ejection fraction

Patient or population: chronic heart failure with preserved ejection fraction
Setting: secondary care
Intervention: ACEI
Comparison: placebo/no treatment

Cardiovascular mortality (RR)
follow‐up: range mean 12 months to mean 26.2 months

RR 0.93
(0.61 to 1.42)

945
(2 RCTs)

⊕⊕⊕⊝
MODERATE ¹

One additional trial (Kitzman 2010) reported that no deaths occurred

Heart failure hospitalisation (RR)
follow‐up: range 6 months to 26.2 months

RR 0.86
(0.64 to 1.15)

1019
(3 RCTs)

⊕⊕⊕⊝
MODERATE ¹

Hyperkalaemia

74 (1 RCTs)

⊕⊝⊝⊝
VERY LOW ^{1 3 4}

One trial (Zi 2003) reported 2 events in the intervention group (N = 36), 0 events in the control group (N = 38) (RR 5.27, 95% CI 0.26 to 106.16)

All‐cause mortality (RR)
follow‐up: range mean 6 months to mean 26.2 months

RR 0.99
(0.71 to 1.38)

1079
(4 RCTs)

⊕⊕⊕⊝
MODERATE ¹

One additional trial (Kitzman 2010) reported that no deaths occurred

Quality of life (Minnesota)
Scale from: 0 to 105
follow‐up: mean 12 months

‐

154
(2 RCTs)

⊕⊕⊝⊝
LOW ^{2 3}

Scale: 0 to 105, lower = better, 5 point difference considered clinically relevant

One trial (SNEGOVIK) reported mean change from baseline of ‐19.8 for intervention and ‐10.7 for control

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

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

ARB compared to placebo or no treatment for chronic heart failure with preserved ejection fraction

Patient or population: chronic heart failure with preserved ejection fraction
Setting: secondary care
Intervention: ARB
Comparison: placebo/no treatment

Cardiovascular mortality (RR)
follow‐up: range mean 12 months to mean 49.5 months

RR 1.02
(0.90 to 1.14)

7254
(3 RCTs)

⊕⊕⊕⊕
HIGH

One additional trial (Parthasarathy 2009) reported that no deaths occurred

Heart failure hospitalisation (RR)
follow‐up: range mean 12 months to mean 49.5 months

RR 0.92
(0.83 to 1.02)

7254
(3 RCTs)

⊕⊕⊕⊕
HIGH

Hyperkalaemia
follow‐up: range 36.6 months to 49.5 months

RR 1.88
(1.07 to 3.33)

7148
(2 RCTs)

⊕⊕⊕⊕
HIGH

All‐cause mortality (RR)
follow up: range 1 years to 4.4 years

RR 1.01
(0.92 to 1.11)

7964
(4 RCTs)

⊕⊕⊕⊕
HIGH

One additional trial (Parthasarathy 2009) reported that no deaths occurred

Quality of life (Minnesota)
scale from: 0 to 105
follow‐up: range mean 13.8 weeks to mean 49.5 months

‐

3117
(3 RCTs)

⊕⊕⊕⊕
HIGH

Scale: 0 to 105, lower = better, 5 point difference considered clinically relevant

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

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