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Cochrane Database of Systematic Reviews

Eficacia hipotensora de los betabloqueantes selectivos beta 1 en la hipertensión primaria

Information

DOI:
https://doi.org/10.1002/14651858.CD007451.pub2Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 10 March 2016see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Hypertension Group

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Gavin WK Wong

    Correspondence to: Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada

    [email protected]

  • Heidi N Boyda

    Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada

  • James M Wright

    Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada

Contributions of authors

Gavin Wong took the lead role in searching, identifying and assessing studies, in data extraction and analyses, and in interpreting the data and writing the review.

Heidi Boyda aided in the identifying of the included studies, in verifying the data extraction, and reviewing the final draft of the manuscript.

James Wright formulated the idea for the review, developed the basis for the protocol and participated in the interpretation and writing of the review.

Sources of support

Internal sources

  • University of British Columbia, Department of Anesthesiology, Pharmacology & Therapeutics, Canada.

External sources

  • Canadian Institutes of Health Research, Canada.

Declarations of interest

Gavin Wong: nothing to declare
Heide Boyda: nothing to declare
James Wright: nothing to declare.

Acknowledgements

The authors would like to acknowledge the help provided by the Cochrane Hypertension Group. We would like to thank Stephen Adams for retrieving the articles.

Version history

Published

Title

Stage

Authors

Version

2016 Mar 10

Blood pressure lowering efficacy of beta‐1 selective beta blockers for primary hypertension

Review

Gavin WK Wong, Heidi N Boyda, James M Wright

https://doi.org/10.1002/14651858.CD007451.pub2

2008 Oct 08

Blood pressure lowering efficacy of beta‐1 selective beta blockers for primary hypertension

Protocol

Gavin WK Wong, Alexandra Laugerotte, James M Wright

https://doi.org/10.1002/14651858.CD007451

Differences between protocol and review

There are no differences between the protocol and review.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

PRISMA study flow diagram
Figures and Tables -
Figure 1

PRISMA study flow diagram

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Funnel plot of nebivolol 5 mg to 20 mg (SBP)
Figures and Tables -
Figure 3

Funnel plot of nebivolol 5 mg to 20 mg (SBP)

Funnel plot of nebivolol 5 mg to 20 mg (DBP)
Figures and Tables -
Figure 4

Funnel plot of nebivolol 5 mg to 20 mg (DBP)

Comparison 1 Nebivolol vs Placebo, Outcome 1 SBP.
Figures and Tables -
Analysis 1.1

Comparison 1 Nebivolol vs Placebo, Outcome 1 SBP.

Comparison 1 Nebivolol vs Placebo, Outcome 2 DBP.
Figures and Tables -
Analysis 1.2

Comparison 1 Nebivolol vs Placebo, Outcome 2 DBP.

Comparison 1 Nebivolol vs Placebo, Outcome 3 Heart rate.
Figures and Tables -
Analysis 1.3

Comparison 1 Nebivolol vs Placebo, Outcome 3 Heart rate.

Comparison 1 Nebivolol vs Placebo, Outcome 4 Pulse Pressure.
Figures and Tables -
Analysis 1.4

Comparison 1 Nebivolol vs Placebo, Outcome 4 Pulse Pressure.

Comparison 1 Nebivolol vs Placebo, Outcome 5 Peak vs Trough SBP.
Figures and Tables -
Analysis 1.5

Comparison 1 Nebivolol vs Placebo, Outcome 5 Peak vs Trough SBP.

Comparison 1 Nebivolol vs Placebo, Outcome 6 Peak vs Trough DBP.
Figures and Tables -
Analysis 1.6

Comparison 1 Nebivolol vs Placebo, Outcome 6 Peak vs Trough DBP.

Comparison 2 Atenolol vs Placebo, Outcome 1 SBP.
Figures and Tables -
Analysis 2.1

Comparison 2 Atenolol vs Placebo, Outcome 1 SBP.

Comparison 2 Atenolol vs Placebo, Outcome 2 DBP.
Figures and Tables -
Analysis 2.2

Comparison 2 Atenolol vs Placebo, Outcome 2 DBP.

Comparison 2 Atenolol vs Placebo, Outcome 3 Heart rate.
Figures and Tables -
Analysis 2.3

Comparison 2 Atenolol vs Placebo, Outcome 3 Heart rate.

Comparison 2 Atenolol vs Placebo, Outcome 4 Pulse pressure.
Figures and Tables -
Analysis 2.4

Comparison 2 Atenolol vs Placebo, Outcome 4 Pulse pressure.

Comparison 3 Metoprolol vs Placebo, Outcome 1 SBP.
Figures and Tables -
Analysis 3.1

Comparison 3 Metoprolol vs Placebo, Outcome 1 SBP.

Comparison 3 Metoprolol vs Placebo, Outcome 2 DBP.
Figures and Tables -
Analysis 3.2

Comparison 3 Metoprolol vs Placebo, Outcome 2 DBP.

Comparison 3 Metoprolol vs Placebo, Outcome 3 Heart rate.
Figures and Tables -
Analysis 3.3

Comparison 3 Metoprolol vs Placebo, Outcome 3 Heart rate.

Comparison 3 Metoprolol vs Placebo, Outcome 4 Pulse pressure.
Figures and Tables -
Analysis 3.4

Comparison 3 Metoprolol vs Placebo, Outcome 4 Pulse pressure.

Comparison 4 Bisoprolol vs placebo, Outcome 1 SBP.
Figures and Tables -
Analysis 4.1

Comparison 4 Bisoprolol vs placebo, Outcome 1 SBP.

Comparison 4 Bisoprolol vs placebo, Outcome 2 DBP.
Figures and Tables -
Analysis 4.2

Comparison 4 Bisoprolol vs placebo, Outcome 2 DBP.

Comparison 4 Bisoprolol vs placebo, Outcome 3 Heart rate.
Figures and Tables -
Analysis 4.3

Comparison 4 Bisoprolol vs placebo, Outcome 3 Heart rate.

Comparison 4 Bisoprolol vs placebo, Outcome 4 Pulse pressure.
Figures and Tables -
Analysis 4.4

Comparison 4 Bisoprolol vs placebo, Outcome 4 Pulse pressure.

Comparison 5 Betaxolol vs Placebo, Outcome 1 SBP.
Figures and Tables -
Analysis 5.1

Comparison 5 Betaxolol vs Placebo, Outcome 1 SBP.

Comparison 5 Betaxolol vs Placebo, Outcome 2 DBP.
Figures and Tables -
Analysis 5.2

Comparison 5 Betaxolol vs Placebo, Outcome 2 DBP.

Comparison 5 Betaxolol vs Placebo, Outcome 3 Heart rate.
Figures and Tables -
Analysis 5.3

Comparison 5 Betaxolol vs Placebo, Outcome 3 Heart rate.

Comparison 5 Betaxolol vs Placebo, Outcome 4 Pulse pressure.
Figures and Tables -
Analysis 5.4

Comparison 5 Betaxolol vs Placebo, Outcome 4 Pulse pressure.

Comparison 6 Bevantolol vs Placebo, Outcome 1 SBP.
Figures and Tables -
Analysis 6.1

Comparison 6 Bevantolol vs Placebo, Outcome 1 SBP.

Comparison 6 Bevantolol vs Placebo, Outcome 2 DBP.
Figures and Tables -
Analysis 6.2

Comparison 6 Bevantolol vs Placebo, Outcome 2 DBP.

Comparison 6 Bevantolol vs Placebo, Outcome 3 Heart rate.
Figures and Tables -
Analysis 6.3

Comparison 6 Bevantolol vs Placebo, Outcome 3 Heart rate.

Comparison 6 Bevantolol vs Placebo, Outcome 4 Pulse pressure.
Figures and Tables -
Analysis 6.4

Comparison 6 Bevantolol vs Placebo, Outcome 4 Pulse pressure.

Comparison 7 Pafenolol vs Placebo, Outcome 1 SBP.
Figures and Tables -
Analysis 7.1

Comparison 7 Pafenolol vs Placebo, Outcome 1 SBP.

Comparison 7 Pafenolol vs Placebo, Outcome 2 DBP.
Figures and Tables -
Analysis 7.2

Comparison 7 Pafenolol vs Placebo, Outcome 2 DBP.

Comparison 7 Pafenolol vs Placebo, Outcome 3 Heart rate.
Figures and Tables -
Analysis 7.3

Comparison 7 Pafenolol vs Placebo, Outcome 3 Heart rate.

Comparison 7 Pafenolol vs Placebo, Outcome 4 Pulse pressure.
Figures and Tables -
Analysis 7.4

Comparison 7 Pafenolol vs Placebo, Outcome 4 Pulse pressure.

Comparison 8 Practolol vs Placebo, Outcome 1 SBP.
Figures and Tables -
Analysis 8.1

Comparison 8 Practolol vs Placebo, Outcome 1 SBP.

Comparison 8 Practolol vs Placebo, Outcome 2 DBP.
Figures and Tables -
Analysis 8.2

Comparison 8 Practolol vs Placebo, Outcome 2 DBP.

Comparison 8 Practolol vs Placebo, Outcome 3 Heart rate.
Figures and Tables -
Analysis 8.3

Comparison 8 Practolol vs Placebo, Outcome 3 Heart rate.

Comparison 8 Practolol vs Placebo, Outcome 4 Pulse pressure.
Figures and Tables -
Analysis 8.4

Comparison 8 Practolol vs Placebo, Outcome 4 Pulse pressure.

Comparison 9 Pooled overall effect, Outcome 1 SBP.
Figures and Tables -
Analysis 9.1

Comparison 9 Pooled overall effect, Outcome 1 SBP.

Comparison 9 Pooled overall effect, Outcome 2 DBP.
Figures and Tables -
Analysis 9.2

Comparison 9 Pooled overall effect, Outcome 2 DBP.

Comparison 9 Pooled overall effect, Outcome 3 Heart rate.
Figures and Tables -
Analysis 9.3

Comparison 9 Pooled overall effect, Outcome 3 Heart rate.

Comparison 9 Pooled overall effect, Outcome 4 Pulse pressure.
Figures and Tables -
Analysis 9.4

Comparison 9 Pooled overall effect, Outcome 4 Pulse pressure.

Comparison 9 Pooled overall effect, Outcome 5 WDAE.
Figures and Tables -
Analysis 9.5

Comparison 9 Pooled overall effect, Outcome 5 WDAE.

Comparison 9 Pooled overall effect, Outcome 6 SBP combined starting dose and 2 x starting dose.
Figures and Tables -
Analysis 9.6

Comparison 9 Pooled overall effect, Outcome 6 SBP combined starting dose and 2 x starting dose.

Comparison 9 Pooled overall effect, Outcome 7 DBP combined starting dose and 2 x starting dose.
Figures and Tables -
Analysis 9.7

Comparison 9 Pooled overall effect, Outcome 7 DBP combined starting dose and 2 x starting dose.

Comparison 9 Pooled overall effect, Outcome 8 Heart rate combined starting dose and 2 x starting dose.
Figures and Tables -
Analysis 9.8

Comparison 9 Pooled overall effect, Outcome 8 Heart rate combined starting dose and 2 x starting dose.

Comparison 9 Pooled overall effect, Outcome 9 Pulse pressure combined starting dose and 2 x starting dose.
Figures and Tables -
Analysis 9.9

Comparison 9 Pooled overall effect, Outcome 9 Pulse pressure combined starting dose and 2 x starting dose.

Comparison 9 Pooled overall effect, Outcome 10 SBP test for 2 x starting dose subgroup difference.
Figures and Tables -
Analysis 9.10

Comparison 9 Pooled overall effect, Outcome 10 SBP test for 2 x starting dose subgroup difference.

Comparison 9 Pooled overall effect, Outcome 11 DBP test for 2 x starting dose subgroup difference.
Figures and Tables -
Analysis 9.11

Comparison 9 Pooled overall effect, Outcome 11 DBP test for 2 x starting dose subgroup difference.

Comparison 9 Pooled overall effect, Outcome 12 Heart rate test for 2 x starting dose subgroup difference.
Figures and Tables -
Analysis 9.12

Comparison 9 Pooled overall effect, Outcome 12 Heart rate test for 2 x starting dose subgroup difference.

Blood pressure lowering effects of beta‐1 blockers compared with placebo for primary hypertension

Patient or population: People with primary hypertension

Intervention: Beta‐1 selective blockers

Comparison: Placebo

Outcomes

mean estimates of combining 1x and 2x starting dose
(95% CI)

No of Participants
(No. of RCT)

Quality of the evidence
(GRADE)

Systolic blood pressure

‐10.4 (‐11.1, ‐9.7)1,2,3

5246 (47)

Low4,5

Diastolic blood pressure

‐8.3 (‐8.7, ‐7.8)1,2,3

5316 (48)

Low4,5

Heart rate

‐10.9 (‐11.5, ‐10.4)1,2

3407 (33)

Low4,5

Pulse pressure

‐1.8 [‐2.3, ‐1.2]1,2

5246 (47)

Very low4,5,6

WDAE

0.9 (0.5, 1.5)

2618 (3)

Low7,8

95% CI: 95% confident interval; WDAE: Withdrawal due to adverse effect.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Footnotes

  1. The data for this analysis is from recommended starting and 2x the starting dose. Combining them provides the best estimate of the subclass effect.

  2. Half of measurements at peak hours and the other half at trough hours.

  3. The mean baseline BP was 156/101 mmHg.

  4. Downgraded due to publication bias, extreme outliers causing significant heterogeneity within some subgroups.

  5. Downgraded due to high risk of detection bias caused by loss of blinding.

  6. Downgraded due to indirectness, none of the studies reported pulse pressure. Pulse pressure was calculated by subtracting DBP from SBP.

  7. Downgraded due to imprecision.

  8. Downgraded due to selective reporting bias.

Figures and Tables -
Comparison 1. Nebivolol vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

13

Mean Difference (Fixed, 95% CI)

Subtotals only

1.1 (0.25 x starting dose) 1.0 & 1.25 mg/day

3

366

Mean Difference (Fixed, 95% CI)

‐4.49 [‐7.15, ‐1.83]

1.2 (0.5 x starting dose) 2.5 mg/day

3

415

Mean Difference (Fixed, 95% CI)

‐4.96 [‐7.66, ‐2.26]

1.3 (starting dose) 5 mg/day

12

1280

Mean Difference (Fixed, 95% CI)

‐8.81 [‐10.23, ‐7.40]

1.4 (2 x starting dose) 10 mg/day

6

1684

Mean Difference (Fixed, 95% CI)

‐6.04 [‐7.47, ‐4.60]

1.5 (4 x starting dose) 20 mg/day

3

652

Mean Difference (Fixed, 95% CI)

‐6.95 [‐9.26, ‐4.63]

1.6 (8 x starting dose) 30, 40 mg/day

3

1155

Mean Difference (Fixed, 95% CI)

‐8.10 [‐9.84, ‐6.36]

2 DBP Show forest plot

13

Mean Difference (Fixed, 95% CI)

Subtotals only

2.1 (0.25 x starting dose) 1.0 & 1.25 mg/day

3

366

Mean Difference (Fixed, 95% CI)

‐3.55 [‐5.17, ‐1.93]

2.2 (0.5 x starting dose) 2.5 mg/day

3

415

Mean Difference (Fixed, 95% CI)

‐4.23 [‐5.76, ‐2.70]

2.3 (starting dose) 5 mg/day

12

1280

Mean Difference (Fixed, 95% CI)

‐6.67 [‐7.54, ‐5.80]

2.4 (2 x starting dose) 10 mg/day

6

1684

Mean Difference (Fixed, 95% CI)

‐5.90 [‐6.78, ‐5.01]

2.5 (4 x starting dose) 20 mg/day

3

652

Mean Difference (Fixed, 95% CI)

‐5.81 [‐7.21, ‐4.41]

2.6 (8 x starting dose) 30, 40 mg/day

3

1155

Mean Difference (Fixed, 95% CI)

‐7.70 [‐8.80, ‐6.61]

3 Heart rate Show forest plot

8

Mean Difference (Fixed, 95% CI)

Subtotals only

3.1 (0.25 x starting dose) 1.25 mg/day

1

136

Mean Difference (Fixed, 95% CI)

‐2.9 [‐5.86, 0.06]

3.2 (0.5 x starting dose) 2.5 mg/day

2

218

Mean Difference (Fixed, 95% CI)

‐3.89 [‐6.18, ‐1.61]

3.3 (starting dose) 5 mg/day

7

487

Mean Difference (Fixed, 95% CI)

‐8.21 [‐9.66, ‐6.76]

3.4 (2 x starting dose) 10 mg/day

3

1120

Mean Difference (Fixed, 95% CI)

‐7.23 [‐8.48, ‐5.99]

3.5 (4 x starting dose) 20 mg/day

2

298

Mean Difference (Fixed, 95% CI)

‐8.43 [‐10.48, ‐6.38]

3.6 (8 x starting dose) 30, 40 mg/day

3

1155

Mean Difference (Fixed, 95% CI)

‐10.94 [‐12.18, ‐9.71]

4 Pulse Pressure Show forest plot

13

Mean Difference (Fixed, 95% CI)

Subtotals only

4.1 (0.25 x starting dose) 1.0 & 1.25 mg/day

3

366

Mean Difference (Fixed, 95% CI)

‐0.88 [‐3.21, 1.45]

4.2 (0.5 x starting dose) 2.5 mg/day

3

415

Mean Difference (Fixed, 95% CI)

‐0.95 [‐3.32, 1.41]

4.3 (starting dose) 5 mg/day

12

1314

Mean Difference (Fixed, 95% CI)

‐1.62 [‐2.83, ‐0.41]

4.4 (2 x starting dose) 10 mg/day

6

1684

Mean Difference (Fixed, 95% CI)

‐0.19 [‐1.47, 1.08]

4.5 (4 x starting dose) 20 mg/day

3

652

Mean Difference (Fixed, 95% CI)

‐1.25 [‐3.38, 0.89]

4.6 (8 x starting dose) 30, 40 mg/day

3

1155

Mean Difference (Fixed, 95% CI)

‐0.37 [‐1.94, 1.20]

5 Peak vs Trough SBP Show forest plot

4

Mean Difference (Fixed, 95% CI)

Subtotals only

5.1 (0.25 x starting dose) 1.0 & 1.25 mg/day

2

335

Mean Difference (Fixed, 95% CI)

0.30 [‐1.90, 2.49]

5.2 (0.5 x starting dose) 2.5 mg/day

3

415

Mean Difference (Fixed, 95% CI)

‐1.24 [‐3.28, 0.81]

5.3 (starting dose) 5 mg/day

4

817

Mean Difference (Fixed, 95% CI)

1.40 [0.14, 2.66]

5.4 (2 x starting dose) 10 mg/day

4

822

Mean Difference (Fixed, 95% CI)

‐0.17 [‐1.42, 1.08]

5.5 (4 x starting dose) 20 mg/day

3

652

Mean Difference (Fixed, 95% CI)

1.17 [‐0.27, 2.61]

5.6 (8 x starting dose) 30, 40 mg/day

2

331

Mean Difference (Fixed, 95% CI)

‐1.20 [‐3.19, 0.78]

6 Peak vs Trough DBP Show forest plot

4

3372

Mean Difference (Fixed, 95% CI)

‐1.53 [‐1.95, ‐1.11]

6.1 (0.25 x starting dose) 1.0 & 1.25 mg/day

2

335

Mean Difference (Fixed, 95% CI)

‐0.95 [‐2.38, 0.48]

6.2 (0.5 x starting dose) 2.5 mg/day

3

415

Mean Difference (Fixed, 95% CI)

‐1.88 [‐3.12, ‐0.64]

6.3 (starting dose) 5 mg/day

4

817

Mean Difference (Fixed, 95% CI)

‐1.54 [‐2.52, ‐0.57]

6.4 (2 x starting dose) 10 mg/day

4

822

Mean Difference (Fixed, 95% CI)

‐1.06 [‐1.86, ‐0.26]

6.5 (4 x starting dose) 20 mg/day

3

652

Mean Difference (Fixed, 95% CI)

‐1.53 [‐2.41, ‐0.65]

6.6 (8 x starting dose) 30, 40 mg/day

2

331

Mean Difference (Fixed, 95% CI)

‐2.73 [‐3.98, ‐1.49]

Figures and Tables -
Comparison 1. Nebivolol vs Placebo
Comparison 2. Atenolol vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

22

Mean Difference (Fixed, 95% CI)

Subtotals only

1.1 (0.5 x starting dose) 25 mg/day

1

87

Mean Difference (Fixed, 95% CI)

‐7.0 [‐12.55, ‐1.45]

1.2 (starting dose) 50 mg/day

11

669

Mean Difference (Fixed, 95% CI)

‐10.28 [‐11.94, ‐8.62]

1.3 (2 x starting dose) 100 mg/day

12

495

Mean Difference (Fixed, 95% CI)

‐15.34 [‐16.86, ‐13.82]

1.4 (4 x starting dose) 150 & 200 mg/day

3

121

Mean Difference (Fixed, 95% CI)

‐11.29 [‐14.03, ‐8.55]

2 DBP Show forest plot

22

Mean Difference (Fixed, 95% CI)

Subtotals only

2.1 (0.5 x starting dose) 25 mg/day

1

87

Mean Difference (Fixed, 95% CI)

‐4.0 [‐6.76, ‐1.24]

2.2 (starting dose) 50 mg/day

11

657

Mean Difference (Fixed, 95% CI)

‐7.78 [‐8.80, ‐6.76]

2.3 (2 x starting dose) 100 mg/day

12

495

Mean Difference (Fixed, 95% CI)

‐12.91 [‐13.89, ‐11.93]

2.4 (4 x starting dose) 150, 200 mg/day

3

121

Mean Difference (Fixed, 95% CI)

‐8.76 [‐10.56, ‐6.95]

3 Heart rate Show forest plot

17

Mean Difference (Fixed, 95% CI)

Subtotals only

3.1 (0.5 x starting dose) 25 mg/day

1

87

Mean Difference (Fixed, 95% CI)

‐4.0 [‐9.55, 1.55]

3.2 (starting dose) 50 mg/day

7

470

Mean Difference (Fixed, 95% CI)

‐12.04 [‐13.39, ‐10.68]

3.3 (2 x starting dose) 100 mg/day

10

413

Mean Difference (Fixed, 95% CI)

‐13.70 [‐14.83, ‐12.56]

3.4 (4 x starting dose) 150, 200 mg/day

4

129

Mean Difference (Fixed, 95% CI)

‐18.33 [‐20.26, ‐16.41]

4 Pulse pressure Show forest plot

22

Mean Difference (Fixed, 95% CI)

Subtotals only

4.1 (0.5 x starting dose) 25 mg/day

1

87

Mean Difference (Fixed, 95% CI)

‐3.0 [‐7.80, 1.80]

4.2 (starting dose) 50 mg/day

11

669

Mean Difference (Fixed, 95% CI)

‐2.30 [‐3.71, ‐0.90]

4.3 (2 x starting dose) 100 mg/day

12

495

Mean Difference (Fixed, 95% CI)

‐2.01 [‐3.24, ‐0.77]

4.4 (4 x starting dose) 150, 200 mg/day

3

121

Mean Difference (Fixed, 95% CI)

‐2.62 [‐4.82, ‐0.42]

Figures and Tables -
Comparison 2. Atenolol vs Placebo
Comparison 3. Metoprolol vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

9

Mean Difference (Fixed, 95% CI)

Subtotals only

1.1 (0.25 x starting dose) 25 mg/day

2

424

Mean Difference (Fixed, 95% CI)

‐6.33 [‐9.22, ‐3.44]

1.2 (0.5 x starting dose) 50 mg/day

2

339

Mean Difference (Fixed, 95% CI)

‐6.30 [‐9.47, ‐3.13]

1.3 (starting dose) 100 mg/day

3

410

Mean Difference (Fixed, 95% CI)

‐5.35 [‐8.12, ‐2.58]

1.4 (2 x starting dose) 200 mg/day

5

284

Mean Difference (Fixed, 95% CI)

‐11.54 [‐14.37, ‐8.71]

1.5 (4 x starting dose) 400 mg/day

2

193

Mean Difference (Fixed, 95% CI)

‐10.91 [‐15.42, ‐6.40]

2 DBP Show forest plot

9

Mean Difference (Fixed, 95% CI)

Subtotals only

2.1 (0.25 x starting dose) 25 mg/day

2

424

Mean Difference (Fixed, 95% CI)

‐3.64 [‐5.44, ‐1.85]

2.2 (0.5 x starting dose) 50 mg/day

2

339

Mean Difference (Fixed, 95% CI)

‐4.56 [‐6.42, ‐2.70]

2.3 (starting dose) 100 & 120 mg/day

3

410

Mean Difference (Fixed, 95% CI)

‐4.74 [‐6.50, ‐2.98]

2.4 (2 x starting dose) 200 mg/day

5

284

Mean Difference (Fixed, 95% CI)

‐10.25 [‐11.99, ‐8.51]

2.5 (4 x starting dose) 400 mg/day

2

193

Mean Difference (Fixed, 95% CI)

‐7.71 [‐10.72, ‐4.69]

3 Heart rate Show forest plot

5

Mean Difference (Fixed, 95% CI)

Subtotals only

3.1 (0.5 x starting dose) 50 mg/day

1

94

Mean Difference (Fixed, 95% CI)

‐5.6 [‐10.03, ‐1.17]

3.2 (starting dose) 100 & 120 mg/day

1

24

Mean Difference (Fixed, 95% CI)

‐15.0 [‐18.92, ‐11.08]

3.3 (2 x starting dose) 200 mg/day

2

40

Mean Difference (Fixed, 95% CI)

‐13.25 [‐17.04, ‐9.46]

3.4 (4 x starting dose) 400 mg/day

1

8

Mean Difference (Fixed, 95% CI)

‐20.00 [‐25.88, ‐14.12]

4 Pulse pressure Show forest plot

9

Mean Difference (Fixed, 95% CI)

Subtotals only

4.1 (0.25 x starting dose) 25 mg/day

2

424

Mean Difference (Fixed, 95% CI)

‐2.70 [‐5.23, ‐0.17]

4.2 (0.5 x starting dose) 50 mg/day

2

339

Mean Difference (Fixed, 95% CI)

‐1.74 [‐4.52, 1.04]

4.3 (starting dose) 100 mg/day

3

410

Mean Difference (Fixed, 95% CI)

‐0.58 [‐3.01, 1.85]

4.4 (2 x starting dose) 200 mg/day

5

284

Mean Difference (Fixed, 95% CI)

‐1.22 [‐3.62, 1.18]

4.5 (4 x starting dose) 400 mg/day

2

193

Mean Difference (Fixed, 95% CI)

‐3.30 [‐7.29, 0.69]

Figures and Tables -
Comparison 3. Metoprolol vs Placebo
Comparison 4. Bisoprolol vs placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

6

Mean Difference (Fixed, 95% CI)

Subtotals only

1.1 (starting dose) 5 mg/day

5

422

Mean Difference (Fixed, 95% CI)

‐11.40 [‐13.67, ‐9.13]

1.2 (2 x starting dose) 10 mg/day

2

134

Mean Difference (Fixed, 95% CI)

‐7.03 [‐11.07, ‐2.99]

1.3 (4 x starting dose) 20 mg/day

1

121

Mean Difference (Fixed, 95% CI)

‐7.6 [‐12.60, ‐2.60]

2 DBP Show forest plot

7

Mean Difference (Fixed, 95% CI)

Subtotals only

2.1 (starting dose) 5 mg/day

6

462

Mean Difference (Fixed, 95% CI)

‐8.16 [‐9.49, ‐6.84]

2.2 (2 x starting dose) 10 mg/day

3

173

Mean Difference (Fixed, 95% CI)

‐7.44 [‐9.88, ‐5.01]

2.3 (4 x starting dose) 20 mg/day

1

121

Mean Difference (Fixed, 95% CI)

‐8.5 [‐11.56, ‐5.44]

3 Heart rate Show forest plot

6

Mean Difference (Fixed, 95% CI)

Subtotals only

3.1 (starting dose) 5 mg/day

5

236

Mean Difference (Fixed, 95% CI)

‐6.91 [‐8.82, ‐4.99]

3.2 (2 x starting dose) 10 mg/day

3

173

Mean Difference (Fixed, 95% CI)

‐10.19 [‐12.87, ‐7.52]

3.3 (4 x starting dose) 20 mg/day

1

121

Mean Difference (Fixed, 95% CI)

‐11.1 [‐14.98, ‐7.22]

4 Pulse pressure Show forest plot

6

Mean Difference (Fixed, 95% CI)

Subtotals only

4.1 (starting dose) 5 mg/day

5

422

Mean Difference (Fixed, 95% CI)

‐3.35 [‐5.32, ‐1.38]

4.2 (2 x starting dose) 10 mg/day

2

134

Mean Difference (Fixed, 95% CI)

1.65 [‐1.96, 5.26]

4.3 (4 x starting dose) 20 mg/day

1

121

Mean Difference (Fixed, 95% CI)

0.9 [‐3.45, 5.25]

Figures and Tables -
Comparison 4. Bisoprolol vs placebo
Comparison 5. Betaxolol vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

2

Mean Difference (Fixed, 95% CI)

Subtotals only

1.1 (0.5 x starting dose) 5 mg/day

1

148

Mean Difference (Fixed, 95% CI)

‐5.81 [‐10.55, ‐1.07]

1.2 (starting dose) 10 mg/day

1

146

Mean Difference (Fixed, 95% CI)

‐8.2 [‐12.94, ‐3.46]

1.3 (2 x starting dose) 20 mg/day

2

477

Mean Difference (Fixed, 95% CI)

‐11.25 [‐13.21, ‐9.29]

2 DBP Show forest plot

2

Mean Difference (Fixed, 95% CI)

Subtotals only

2.1 (0.5 x starting dose) 5 mg/day

1

148

Mean Difference (Fixed, 95% CI)

‐3.8 [‐6.54, ‐1.06]

2.2 (starting dose) 10 mg/day

1

146

Mean Difference (Fixed, 95% CI)

‐6.5 [‐9.24, ‐3.76]

2.3 (2 x starting dose) 20 mg/day

2

477

Mean Difference (Fixed, 95% CI)

‐7.94 [‐9.17, ‐6.71]

3 Heart rate Show forest plot

2

Mean Difference (Fixed, 95% CI)

Subtotals only

3.1 (0.5 x starting dose) 5 mg/day

1

148

Mean Difference (Fixed, 95% CI)

‐7.4 [‐10.34, ‐4.46]

3.2 (starting dose) 10 mg/day

1

146

Mean Difference (Fixed, 95% CI)

‐8.2 [‐11.14, ‐5.26]

3.3 (2 x starting dose) 20 mg/day

2

477

Mean Difference (Fixed, 95% CI)

‐13.40 [‐15.03, ‐11.77]

4 Pulse pressure Show forest plot

2

Mean Difference (Fixed, 95% CI)

Subtotals only

4.1 (0.5x starting dose) 5 mg/day

1

148

Mean Difference (Fixed, 95% CI)

‐1.1 [‐5.24, 3.04]

4.2 (starting dose) 10 mg/day

1

146

Mean Difference (Fixed, 95% CI)

‐1.7 [‐5.84, 2.44]

4.3 (2 x starting dose) 20 mg/day

2

477

Mean Difference (Fixed, 95% CI)

‐3.26 [‐5.00, ‐1.52]

Figures and Tables -
Comparison 5. Betaxolol vs Placebo
Comparison 6. Bevantolol vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 Bevantolol 100mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐13.0 [‐29.57, 3.57]

1.2 Bevantolol 200mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐9.0 [‐25.57, 7.57]

1.3 Bevantolol 300mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐7.0 [‐23.57, 9.57]

1.4 Bevantolol 400mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐8.0 [‐24.57, 8.57]

2 DBP Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 Bevantolol 100mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐5.0 [‐15.52, 5.52]

2.2 Bevantolol 200mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐9.0 [‐19.52, 1.52]

2.3 Bevantolol 300mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐9.0 [‐19.52, 1.52]

2.4 Bevantolol 400mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐10.0 [‐20.52, 0.52]

3 Heart rate Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 Bevantolol 100mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐13.0 [‐29.57, 3.57]

3.2 Bevantolol 200mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐9.0 [‐25.57, 7.57]

3.3 Bevantolol 300mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐7.0 [‐23.57, 9.57]

3.4 Bevantolol 400mg/day

1

35

Mean Difference (IV, Fixed, 95% CI)

‐8.0 [‐24.57, 8.57]

4 Pulse pressure Show forest plot

1

Mean Difference (Fixed, 95% CI)

Subtotals only

4.1 Bevantolol 100mg/day

1

Mean Difference (Fixed, 95% CI)

‐8.0 [‐22.52, 6.52]

4.2 Bevantolol 200mg/day

1

Mean Difference (Fixed, 95% CI)

0.0 [‐14.52, 14.52]

4.3 Bevantolol 300mg/day

1

Mean Difference (Fixed, 95% CI)

2.0 [‐12.56, 16.56]

4.4 Bevantolol 400mg/day

1

Mean Difference (Fixed, 95% CI)

2.0 [‐12.52, 16.52]

Figures and Tables -
Comparison 6. Bevantolol vs Placebo
Comparison 7. Pafenolol vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 25 mg/day

1

21

Mean Difference (IV, Fixed, 95% CI)

3.0 [‐11.79, 17.79]

1.2 50 mg/day

2

33

Mean Difference (IV, Fixed, 95% CI)

‐5.94 [‐17.57, 5.68]

1.3 100 mg/day

1

14

Mean Difference (IV, Fixed, 95% CI)

‐6.0 [‐22.94, 10.94]

2 DBP Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

2.1 25 mg/day

1

21

Mean Difference (IV, Fixed, 95% CI)

‐8.0 [‐16.73, 0.73]

2.2 50 mg/day

2

33

Mean Difference (IV, Fixed, 95% CI)

‐4.41 [‐11.22, 2.40]

2.3 100 mg/day

1

14

Mean Difference (IV, Fixed, 95% CI)

‐2.0 [‐12.75, 8.75]

3 Heart rate Show forest plot

2

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 25 mg/day

1

21

Mean Difference (IV, Fixed, 95% CI)

‐3.0 [‐12.93, 6.93]

3.2 50 mg/day

2

33

Mean Difference (IV, Fixed, 95% CI)

‐8.14 [‐15.91, ‐0.36]

3.3 100 mg/day

1

14

Mean Difference (IV, Fixed, 95% CI)

‐20.0 [‐32.60, ‐7.40]

4 Pulse pressure Show forest plot

2

Mean Difference (Fixed, 95% CI)

Subtotals only

4.1 25 mg/day

1

21

Mean Difference (Fixed, 95% CI)

11.0 [‐1.82, 23.82]

4.2 50 mg/day

2

33

Mean Difference (Fixed, 95% CI)

‐1.75 [‐11.86, 8.37]

4.3 100 mg/day

1

14

Mean Difference (Fixed, 95% CI)

‐4.0 [‐18.86, 10.86]

Figures and Tables -
Comparison 7. Pafenolol vs Placebo
Comparison 8. Practolol vs Placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

1

24

Mean Difference (Fixed, 95% CI)

‐21.2 [‐29.31, ‐13.09]

1.1 Practolol 600mg/day

1

24

Mean Difference (Fixed, 95% CI)

‐21.2 [‐29.31, ‐13.09]

2 DBP Show forest plot

1

24

Mean Difference (Fixed, 95% CI)

‐13.9 [‐17.00, ‐8.80]

2.1 Practolol 600mg/day

1

24

Mean Difference (Fixed, 95% CI)

‐13.9 [‐17.00, ‐8.80]

3 Heart rate Show forest plot

1

24

Mean Difference (Fixed, 95% CI)

‐14.0 [‐21.45, ‐6.55]

3.1 Practolol 600mg/day

1

24

Mean Difference (Fixed, 95% CI)

‐14.0 [‐21.45, ‐6.55]

4 Pulse pressure Show forest plot

1

24

Mean Difference (Fixed, 95% CI)

‐7.30 [‐14.41, ‐0.19]

4.1 Practolol 600mg/day

1

24

Mean Difference (Fixed, 95% CI)

‐7.30 [‐14.41, ‐0.19]

Figures and Tables -
Comparison 8. Practolol vs Placebo
Comparison 9. Pooled overall effect

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

50

Mean Difference (Fixed, 95% CI)

Subtotals only

1.1 0.25 x starting dose

5

790

Mean Difference (Fixed, 95% CI)

‐5.34 [‐7.29, ‐3.38]

1.2 0.5 x starting dose

7

941

Mean Difference (Fixed, 95% CI)

‐5.71 [‐7.59, ‐3.82]

1.3 starting dose

30

2879

Mean Difference (Fixed, 95% CI)

‐9.29 [‐10.21, ‐8.38]

1.4 2 x starting dose

27

3026

Mean Difference (Fixed, 95% CI)

‐10.58 [‐11.45, ‐9.71]

1.5 4 x starting dose

9

1087

Mean Difference (Fixed, 95% CI)

‐8.90 [‐10.47, ‐7.34]

1.6 8 x starting dose

2

331

Mean Difference (Fixed, 95% CI)

‐8.29 [‐11.24, ‐5.35]

2 DBP Show forest plot

51

Mean Difference (Fixed, 95% CI)

Subtotals only

2.1 0.25 x starting dose

5

790

Mean Difference (Fixed, 95% CI)

‐3.59 [‐4.79, ‐2.39]

2.2 0.5 x starting dose

7

941

Mean Difference (Fixed, 95% CI)

‐4.27 [‐5.31, ‐3.22]

2.3 starting dose

31

2907

Mean Difference (Fixed, 95% CI)

‐7.06 [‐7.62, ‐6.51]

2.4 2 x starting dose

28

3065

Mean Difference (Fixed, 95% CI)

‐8.92 [‐9.47, ‐8.38]

2.5 4 x starting dose

9

1087

Mean Difference (Fixed, 95% CI)

‐7.17 [‐8.15, ‐6.18]

2.6 8 x starting dose

2

331

Mean Difference (Fixed, 95% CI)

‐7.20 [‐8.99, ‐5.40]

3 Heart rate Show forest plot

37

Mean Difference (Fixed, 95% CI)

Subtotals only

3.1 0.25 x starting dose

1

136

Mean Difference (Fixed, 95% CI)

‐2.9 [‐5.86, 0.06]

3.2 0.5 x starting dose

5

499

Mean Difference (Fixed, 95% CI)

‐4.34 [‐6.21, ‐2.47]

3.3 starting dose

20

1315

Mean Difference (Fixed, 95% CI)

‐9.80 [‐10.65, ‐8.94]

3.4 2 x starting dose

20

2175

Mean Difference (Fixed, 95% CI)

‐11.33 [‐12.06, ‐10.61]

3.5 4 x starting dose

8

556

Mean Difference (Fixed, 95% CI)

‐13.71 [‐15.00, ‐12.43]

3.6 8 x starting dose

2

331

Mean Difference (Fixed, 95% CI)

‐9.19 [‐11.21, ‐7.18]

4 Pulse pressure Show forest plot

50

Mean Difference (Fixed, 95% CI)

Subtotals only

4.1 0.25 x starting dose

5

790

Mean Difference (Fixed, 95% CI)

‐1.72 [‐3.43, ‐0.00]

4.2 0.5 x starting dose

7

941

Mean Difference (Fixed, 95% CI)

‐1.48 [‐3.13, 0.17]

4.3 starting dose

30

2913

Mean Difference (Fixed, 95% CI)

0.00 [‐2.78, ‐1.22]

4.4 2 x starting dose

27

3026

Mean Difference (Fixed, 95% CI)

‐1.39 [‐2.14, ‐0.65]

4.5 4 x starting dose

9

1087

Mean Difference (Fixed, 95% CI)

‐1.80 [‐3.16, ‐0.44]

4.6 8 x starting dose

2

331

Mean Difference (Fixed, 95% CI)

‐1.04 [‐3.67, 1.60]

5 WDAE Show forest plot

3

2618

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.50, 1.45]

6 SBP combined starting dose and 2 x starting dose Show forest plot

47

5246

Mean Difference (Fixed, 95% CI)

‐10.42 [‐11.11, ‐9.72]

6.1 starting dose

30

2509

Mean Difference (Fixed, 95% CI)

‐9.71 [‐10.75, ‐8.67]

6.2 2 x starting dose

27

2737

Mean Difference (Fixed, 95% CI)

‐10.99 [‐11.93, ‐10.06]

7 DBP combined starting dose and 2 x starting dose Show forest plot

48

5316

Mean Difference (Fixed, 95% CI)

‐8.27 [‐8.69, ‐7.84]

7.1 starting dose

31

2540

Mean Difference (Fixed, 95% CI)

‐7.23 [‐7.85, ‐6.60]

7.2 2x starting dose

28

2776

Mean Difference (Fixed, 95% CI)

‐9.16 [‐9.74, ‐8.58]

8 Heart rate combined starting dose and 2 x starting dose Show forest plot

33

3407

Mean Difference (Fixed, 95% CI)

‐10.93 [‐11.48, ‐10.37]

8.1 starting dose

20

1268

Mean Difference (Fixed, 95% CI)

‐10.03 [‐10.90, ‐9.17]

8.2 2 x starting dose

20

2139

Mean Difference (Fixed, 95% CI)

‐11.57 [‐12.30, ‐10.84]

9 Pulse pressure combined starting dose and 2 x starting dose Show forest plot

47

5246

Mean Difference (Fixed, 95% CI)

‐1.76 [‐2.34, ‐1.19]

9.1 starting dose

30

2509

Mean Difference (Fixed, 95% CI)

‐2.09 [‐2.94, ‐1.23]

9.2 2 x starting dose

27

2737

Mean Difference (Fixed, 95% CI)

‐1.49 [‐2.27, ‐0.71]

10 SBP test for 2 x starting dose subgroup difference Show forest plot

26

2197

Mean Difference (Fixed, 95% CI)

‐11.27 [‐12.22, ‐10.32]

10.1 Atenolol

12

495

Mean Difference (Fixed, 95% CI)

‐15.34 [‐16.86, ‐13.82]

10.2 Nebivolol

5

855

Mean Difference (Fixed, 95% CI)

‐5.26 [‐7.19, ‐3.34]

10.3 Metoprolol

5

284

Mean Difference (Fixed, 95% CI)

‐11.54 [‐14.37, ‐8.71]

10.4 Bisoprolol

2

134

Mean Difference (Fixed, 95% CI)

‐7.03 [‐11.07, ‐2.99]

10.5 Betaxolol

2

429

Mean Difference (Fixed, 95% CI)

‐11.63 [‐13.73, ‐9.53]

11 DBP test for 2 x starting dose subgroup difference Show forest plot

27

2236

Mean Difference (Fixed, 95% CI)

‐9.47 [‐10.06, ‐8.88]

11.1 Atenolol

12

495

Mean Difference (Fixed, 95% CI)

‐12.91 [‐13.89, ‐11.93]

11.2 Nebivolol

5

855

Mean Difference (Fixed, 95% CI)

‐5.82 [‐6.99, ‐4.65]

11.3 Metoprolol

5

284

Mean Difference (Fixed, 95% CI)

‐10.25 [‐11.99, ‐8.51]

11.4 Bisoprolol

3

173

Mean Difference (Fixed, 95% CI)

‐7.44 [‐9.88, ‐5.01]

11.5 Betaxolol

2

429

Mean Difference (Fixed, 95% CI)

‐8.08 [‐9.39, ‐6.77]

12 Heart rate test for 2 x starting dose subgroup difference Show forest plot

19

1346

Mean Difference (Fixed, 95% CI)

‐12.24 [‐13.05, ‐11.42]

12.1 Atenolol

10

413

Mean Difference (Fixed, 95% CI)

‐13.70 [‐14.83, ‐12.56]

12.2 Nebivolol

2

291

Mean Difference (Fixed, 95% CI)

‐5.94 [‐7.98, ‐3.90]

12.3 Metoprolol

2

40

Mean Difference (Fixed, 95% CI)

‐13.25 [‐17.04, ‐9.46]

12.4 Bisoprolol

3

173

Mean Difference (Fixed, 95% CI)

‐10.19 [‐12.87, ‐7.52]

12.5 Betaxolol

2

429

Mean Difference (Fixed, 95% CI)

‐14.43 [‐16.35, ‐12.51]

Figures and Tables -
Comparison 9. Pooled overall effect