Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections - Schuetz, P - 2017
Philipp Schuetz Yannick Wirz Ramon Sager Mirjam Christ‐Crain Daiana Stolz Michael Tamm Lila Bouadma Charles E Luyt Michel Wolff Jean Chastre
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Cochrane Database of Systematic Reviews

Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections

Information

DOI:

https://doi.org/10.1002/14651858.CD007498.pub3Copy DOI

Database:

Cochrane Database of Systematic Reviews

Version published:

Type:

Intervention

Stage:

Review

Cochrane Editorial Group:

Cochrane Acute Respiratory Infections Group

Copyright:

Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

Philipp Schuetz

Correspondence to: Medical University Department, Kantonsspital Aarau, Aarau, Switzerland

[email protected]

Department of Endocrinology/Metabolism/Clinical Nutrition, Department of Internal Medicine, Kantonsspital Aarau, Aarau, Switzerland

Medical Faculty, University of Basel, Basel, Switzerland

Yannick Wirz

Medical University Department, Kantonsspital Aarau, Aarau, Switzerland

Ramon Sager

Medical University Department, Kantonsspital Aarau, Aarau, Switzerland

Mirjam Christ‐Crain

Clinic for Endocrinology, Diabetes and Metabolism, Department of Clinical Research, University Hospital Basel, University of Basel, Basel, Switzerland

Daiana Stolz

Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland

Michael Tamm

Clinic of Pneumology and Pulmonary Cell Research, University Hospital Basel, Basel, Switzerland

Lila Bouadma

Service de Réanimation Médicale, Hôpital Bichat‐Claude Bernard, Université Paris 7‐Denis‐Diderot, Paris, France

Charles E Luyt

Service de Réanimation Médicale, Groupe Hospitalier Pitié‐Salpêtrière, Assistance Publique–Hôpitaux de Paris, Université Paris 6‐Pierre‐et‐Marie‐Curie, Paris, France

Michel Wolff

Service de Réanimation Médicale, Université Paris 7‐Denis‐Diderot, Paris, France

Jean Chastre

Service de Réanimation Médicale, Université Paris 6‐Pierre‐et‐Marie‐Curie, Paris, France

Florence Tubach

Département Biostatistique, Santé Publique et Information Médicale, AP‐HP, Groupe Hospitalier Pitié‐Salpêtrière Charles‐Foix, INSERM CIC‐P 1421, Sorbonne Universités, UPMC Univ Paris 06, Paris, France

Kristina B Kristoffersen

Department of Infectious Diseases, Aarhus University Hospital, Aarhus N, Denmark

Olaf Burkhardt

Department of Pulmonary Medicine, Medizinische Hochschule Hannover, Hannover, Germany

Tobias Welte

Department of Pulmonary Medicine, Medizinische Hochschule Hannover, Hannover, Germany

German Center for Lung Reearch (DZL), Gießen, Germany

Stefan Schroeder

Department of Anesthesiology and Intensive Care Medicine, Krankenhaus Dueren, Dueren, Germany

Vandack Nobre

Department of Internal Medicine, School of Medicine, Universidade Federal de Minas Gerais, Minas Gerais, Brazil

Long Wei

Department of Internal and Geriatric Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital (East campus), Shanghai, China

Heiner C C Bucher

Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland

Medical Faculty, University Hospital Basel, Basel, Switzerland

Neera Bhatnagar

Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada

Djillali Annane

Department of Critical Care, Hyperbaric Medicine and Home Respiratory Unit, Center for Neuromuscular Diseases; Raymond Poincaré Hospital (AP‐HP), Garches, France

Konrad Reinhart

Department of Anesthesiology and Intensive Care Medicine, Jena University Hospital, Jena, Germany

Angela Branche

Department of Medicine, Division of Infectious Diseases, University of Rochester School of Medicine, Rochester, USA

Pierre Damas

Department of General Intensive Care, University Hospital of Liege, Domaine universitaire de Liège, Liege, Belgium

Maarten Nijsten

University Medical Centre, University of Groningen, Groningen, Netherlands

Dylan W de Lange

Department of Intensive Care, University Medical Center Utrecht, Utrecht, Netherlands

Rodrigo O Deliberato

Critical Care Unit, Hospital Israelita Albert Einstein, São Paulo, Brazil

Stella SS Lima

Graduate Program in Infectious Diseases and Tropical Medicine, Department of Internal Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

Vera Maravić‐Stojković

Immunology Laboratory, Dedinje Cardiovascular Institute, Belgrade, Serbia

Alessia Verduri

Department of Medical and Surgical Sciences, Policlinico di Modena, University of Modena and Reggio Emilia, Modena, Italy

Bin Cao

Center for Respiratory Diseases, Department of Pulmonary and Critical Care Medicine, China‐Japan Friendship Hospital, National Clinical Research Center of Respiratory Diseases, Capital Medical University, Beijing, China

Yahya Shehabi

Critical Care and Peri‐operative Medicine, Monash Health, Melbourne, Australia

School of Clinical Sciences, Faculty of Medicine Nursing and Health Sciences, Monash University, Melbourne, Australia

Albertus Beishuizen

Department of Intensive Care, Medisch Spectrum Twente, Enschede, Netherlands

Jens‐Ulrik S Jensen

Department of Respiratory Medicine, Copenhagen University Hospital, Bispebjerg og Frederiksberg, Copenhagen NV, Denmark

CHIP, Department of Infectious Diseases and Rheumatology, Finsencentret, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

Caspar Corti

Department of Respiratory Medicine, Copenhagen University Hospital, Bispebjerg og Frederiksberg, Copenhagen NV, Denmark

Jos A Van Oers

Intensive Care Unit, Elisabeth Tweesteden Ziekenhuis, Tilburg, Netherlands

Ann R Falsey

Department of Medicine, Division of Infectious Diseases, University of Rochester School of Medicine, Rochester, USA

Evelien de Jong

Department of Intensive Care, VU University Medical Center, Amsterdam, Netherlands

Carolina F Oliveira

Department of Internal Medicine, School of Medcine, Federal University of Minas Gerais, Belo Horizonte, Brazil

Bianca Beghe

Department of Medical and Surgical Sciences, AOU Policlinico di Modena, Moderna, Italy

Matthias Briel

Medical Faculty, University of Basel, Basel, Switzerland

Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland

Beat Mueller

Medical University Department, Kantonsspital Aarau, Aarau, Switzerland

Department of Endocrinology/Metabolism/Clinical Nutrition, Department of Internal Medicine, Kantonsspital Aarau, Aarau, Switzerland

Medical Faculty, University of Basel, Basel, Switzerland

Contributions of authors

Philipp Schuetz, Beat Mueller, Heiner Bucher, and Matthias Briel conceived the study and wrote the initial protocol.

Philipp Schuetz and Matthias Briel performed the analysis of the initial review, and Philipp Schuetz, Yannick Wirz, and Ramon Sager performed the analysis of the 2017 update including the writing of the manuscript. Philipp Schuetz, Mirjam Christ‐Crain, Daiana Stolz, Michael Tamm, Lila Bouadma, Charles E Luyt, Michel Wolff, Jean Chastre, Florence Tubach, Kristina B Kristoffersen, Olaf Burkhardt, Tobias Welte, Stefan Schroeder, Vandack Nobre, Long Wei, Heiner C Bucher, Djillali Annane, Konrad Reinhart, Angela Branche, Pierre Damas, Maarten Nijsten, Dylan W de Lange, Rodrigo O Deliberato, Stella SS Lima, Vera Maravić‐Stojković, Alessia Verduri, Bin Cao, Yahya Shehabi,, Albertus Beishuizen, Jens‐Ulrik S Jensen, Caspar Corti, Matthias Briel, Beat Mueller, Jos A Van Oers, Ann R Falsey, and Evelien de Jong are investigators of included trials, provided data from their respective trials, and resolved queries about their trial data.

All authors amended and commented on the manuscript and approved the final version. Philipp Schuetz, Beat Mueller, and Matthias Briel oversaw the study and act as guarantors.

Sources of support

Internal sources

No sources of support supplied

External sources

Gottfried and Julia Bangerter‐Rhyner‐Foundation, the Swiss Foundation for Grants in Biology and Medicine and santésuisse, Switzerland.

Unrestricted research grant to cover salary time related to this review

National Institute for Health Research, UK.

This update was supported by the National Institute for Health Research, via Cochrane Infrastructure and Cochrane Programme Grant funding (NIHR Cochrane Programme Grant 16‐72‐15) to the Acute Respiratory Infections Group. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, National Health Service or the Department of Health.

Declarations of interest

Philipp Schuetz received support (paid to his employer) from Thermo Fisher, Roche Diagnostics, Abbott and bioMerieux to attend meetings and fulfil speaking engagements. These conflicts breach Cochrane's Commercial Sponsorship Policy (Clause 3), therefore Philipp Schuetz will step down as lead author at the next update of the review. Dr Schuetz's declared conflicts were referred to the Funding Arbiter Panel and Cochrane’s Deputy Editor‐in‐Chief who have agreed this course of action but as an exception which does not set a precedent for similar situations in the future.

Beat Mueller reports that within the last 3 years he was part of the speaker bureau of B·R·A·H·M·S and bioMérieux to give educational talks. His institution received compensation for flight and travel expenses, and to cover his absence from work.

Yannick Wirz: None known.

Ramon Sager: None known.

Mirjam Christ‐Crain received support from B·R·A·H·M·S and bioMérieux to attend meetings and fulfilled speaking engagements.

Daiana Stolz received fees for lectures or occasional advisory committees from Boehringer Ingelheim, Almirall, Novartis, Glaxo, AstraZeneca, and Roche. Dr Stolz's institution received unrestricted research grants from ResMed, Weinmann AG, AstraZeneca, Boston Scientific, and Curetis AG.

Michael Tamm: None known.

Lila Bouadma: None known.

Charles E Luyt received lecture fees from B·R·A·H·M·S and Merck Sharp & Dohme‐Chibret.

Michel Wolff received consulting and lectures fees from Merck Sharp & Dohme‐Chibret, Janssen‐Cilag, Gilead, and Astellas Pharma.

Jean Chastre received consulting and lecture fees from Pfizer, B·R·A·H·M·S, Wyeth, Johnson & Johnson, Nektar‐Bayer, and Arpida.

Florence Tubach: My institution received some funds from B·R·A·H·M·S for implementing the PRORATA trial, whose data are involved in the review.

Kristina B Kristoffersen: None known.

Olaf Burkhardt received research support from B·R·A·H·M·S.

Tobias Welte received lecture fees and research support from B·R·A·H·M·S.

Stefan Schroeder received lecture fees and research support from B·R·A·H·M·S.

Vandack Nobre: None known.

Long Wei: None known.

Heiner C Bucher: None known.

Neera Bhatnagar: None known.

Djillali Annane: None known.

Konrad Reinhart received fees for consultancy from Adrenomed, Henningsdorf Berlin, Germany; holds equity in InflaRx, Jena, Germany; and is unpaid chair of the Global Sepsis Alliance, which receives funds from several companies with interest in sepsis diagnostics.

Angela Branche: This work was partially supported by the National Institutes of Health, National Institute of Allergy and Infectious Diseases (contract HHSN27220120005C). This author has nothing else to declare.

Pierre Damas: None known.

Maarten Nijsten: None known.

Dylan W de Lange: The department where Dylan de Lange worked received financial compensation for a randomisation tool during the SAPS trial.

Rodrigo O Deliberato: None known.

Stella SS Lima: None known.

Vera Maravić‐Stojković: None known.

Alessia Verduri: None known.

Bin Cao: None known.

Yahya Shehabi received unrestricted research and educational grants from Thermo Fisher, bioMérieux, Pfizer, and Orion Pharma.

Albertus Beishuizen: None known.

Jens‐Ulrik S Jensen declares that he was invited to the European Respiratory Society meeting 2016 by Roche Pharmaceuticals. Otherwise, he has no disclosures.

Caspar Corti received an unrestricted grant of USD 2000 from Thermo Fisher Scientific, MA, USA; bioMérieux Denmark ApS supported the study non‐financially.

Jos A Van Oers: None known.

Ann R Falsey: The relationships with noted industry partners had no role or influence in the study.

Evelien de Jong received lecturing fees from Thermo Fisher.

Carolina F Oliveira: None known.

Bianca Beghe: None known.

Matthias Briel: Unrestricted grant from B·R·A·H·M·S AG (now Thermo Fisher) that partially covered working hours to a previous version of this Cochrane Review. B·R·A·H·M·S had no role in the design, conduct, analysis, or writing of our manuscript.

Funding: The initial review was partly funded by unrestricted research grants from B·R·A·H·M·S/Thermo Fisher Scientific, the Gottfried and Julia Bangerter‐Rhyner‐Foundation, the Swiss Foundation for Grants in Biology and Medicine (SSMBS, PASMP3‐127684/1), and santésuisse to cover salary time related to this review. The sponsors had no role in the study design, data collection, data analysis or data interpretation, or writing of the report. No funding was received for this update.

No commercial sponsor had any involvement in the design and conduct of this review, namely collection, management, analysis, and interpretation of the data; and preparation, decision to submit, review, or approval of the manuscript.

Acknowledgements

We thank all participating patients and staff of the clinics of emergency medicine, internal medicine, and departments of clinical chemistry from all participating hospitals for their most helpful support during the individual studies. We also wish to thank the following people for commenting on the draft protocol: Hayley Edmonds, Anette Holm, Renato Seligman, Richard Shoemaker, and Roger Damoiseaux; and for reviewing the draft review we wish to thank Anne Lyddiatt, Noorin Bhimani, Anette Holm, Renato Seligman, Mark Jones, and Roger Damoiseaux. We also thank Qing Wang (for translating Chinese articles) and Benjamin Kasenda (for helping with quality assessment of trials in which the primary investigators were involved).

Version history

Published

Title

Stage

Authors

Version

Differences between protocol and review

We changed the co‐primary endpoint of combined disease‐specific failure at 30 days (mentioned in the protocol) to setting‐specific treatment failure at 30 days as defined above for reasons of standardisation across trials. We limited the analysis of the secondary outcome number of 'sick days' (days with restricted activities from the ARI within 14 days following randomisation) to the primary care trials because other trials did not assess this outcome.

In addition, based on referee comments during the initial editorial process of the initial review (Schuetz 2012), we added further sensitivity analyses to investigate the robustness of our results. Specifically, we performed sensitivity analyses excluding trials with low adherence to PCT algorithms (< 70%) or not reporting adherence. We also performed sensitivity analyses with respect to methodological quality criteria (allocation concealment and blinded outcome assessment). We further performed a sensitivity analysis excluding trials with a follow‐up time for mortality different than one month. We conducted meta‐analyses with aggregated data of included trials to further investigate heterogeneity (inconsistency measure I2 statistic and Cochran Q test) of intervention effects and trial subgroups based on adherence to PCT algorithms.

Keywords

MeSH

Medical Subject Headings Check Words

Humans;

PICOs

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.

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Summary of findings for the main comparison. Procalcitonin algorithm compared to standard care for guiding antibiotic therapy in acute respiratory tract infections

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Table 1. Characteristics of included trials

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Table 2. Baseline characteristics of included participants

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Table 3. Quality assessment of trials

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Table 4. Clinical endpoints overall and stratified by setting and ARI diagnosis

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Table 5. Sensitivity analysis

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Table 6. Antibiotic treatment overall and stratified by setting and ARI diagnosis

Parameter

Control group

PCT group

Measures of effect: adjusted OR or difference (95% CI), P value

P for interaction

Overall

3372

3336

Initiation of antibiotics, n (%)

2894 (86.3%)

2351 (71.5%)

0.27 (0.24 to 0.32), P < 0.001

Duration of antibiotics (days), mean (±SD)

9.4 ± 6.2

8.0 ± 6.5

‐1.83 (‐2.15 to ‐1.50), P < 0.001

Total exposure of antibiotics (days), mean (±SD)

8.1 ± 6.6

5.7 ± 6.6

‐2.43 (‐2.71 to ‐2.15), P < 0.001

Setting‐specific outcomes

Primary care

501

507

Initiation of antibiotics, n (%)

316 (63.1%)

116 (22.9%)

0.13 (0.09 to 0.18), P < 0.001

< 0.001

Duration of antibiotics (days), mean (±SD)

7.3 ± 2.5

7.0 ± 2.8

‐0.52 (‐1.07 to 0.04), P = 0.068

0.064

Total exposure of antibiotics (days), mean (±SD)

4.6 ± 4.1

1.6 ± 3.2

‐3.02 (‐3.45 to ‐2.58), P < 0.001

0.101

Emergency department

1638

1615

Initiation of antibiotics, n (%)

1354 (83.2%)

1119 (71.3%)

0.49 (0.41 to 0.58), P < 0.001

< 0.001

Duration of antibiotics (days), mean (±SD)

9.8 ± 5.4

7.3 ± 5.1

‐2.45 (‐2.86 to ‐2.05), P < 0.001

< 0.001

Intensive care unit

1233

1214

Duration of antibiotics (days), mean (±SD)

9.5 ± 7.4

8.8 ± 7.8

‐1.23 (‐1.82 to ‐0.65), P < 0.001

< 0.001

Total exposure of antibiotics (days), mean (±SD)

9.5 ± 7.4

8.1 ± 7.9

‐1.44 (‐1.99 to ‐0.88), P < 0.001

< 0.001

Disease‐specific outcomes

Community‐acquired pneumonia

1468

1442

Initiation of antibiotics, n (%)

1455 (99.4%)

1340 (92.9%)

0.08 (0.04 to 0.15), P < 0.001

< 0.001

Duration of antibiotics (days), mean (±SD)

10.5 ± 6.2

8.0 ± 5.7

‐2.45 (‐2.87 to ‐2.02), P < 0.001

< 0.001

Total exposure of antibiotics (days), mean (±SD)

10.4 ± 6.2

7.5 ± 5.9

‐2.94 (‐3.38 to ‐2.50), P < 0.001

0.004

Exacerbation of COPD

631

621

Initiation of antibiotics, n (%)

453 (71.8%)

266 (42.8%)

0.29 (0.23 to 0.36), P < 0.001

0.017

Duration of antibiotics (days), mean (±SD)

7.4 ± 5.3

7.2 ± 6.7

‐1.15 (‐2.00 to ‐0.31), P = 0.007

0.003

Total exposure of antibiotics (days), mean (±SD)

5.3 ± 5.6

3.1 ± 5.6

‐2.22 (‐2.83 to ‐1.60), P < 0.001

0.506

Acute bronchitis

287

257

Initiation of antibiotics, n (%)

189 (65.9%)

68 (26.5%)

0.18 (0.12 to 0.26), P < 0.001

< 0.001

Duration of antibiotics (days), mean (±SD)

7.1 ± 3.0

6.4 ± 3.5

‐0.35 (‐1.15 to 0.45), P = 0.393

0.359

Total exposure of antibiotics (days), mean (±SD)

4.7 ± 4.2

1.7 ± 3.3

‐2.95 (‐3.59 to ‐2.31), P < 0.001

0.33

Ventilator‐associated pneumonia

186

194

Initiation of antibiotics, n (%)

186 (100.0%)

193 (99.5%)

NA

NA

Duration of antibiotics (days), mean (±SD)

13.1 ± 7.9

10.8 ± 8.7

‐2.22 (‐3.80 to ‐0.65), P = 0.006

0.253

Total exposure of antibiotics (days), mean (±SD)

13.1 ± 7.9

10.8 ± 8.7

‐2.45 (‐4.09 to ‐0.82), P = 0.003

0.786

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Comparison 1. Procalcitonin algorithm versus no procalcitonin algorithm stratified by clinical setting

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality at 30 days Show forest plot

32

10046

Odds Ratio (M‐H, Random, 95% CI)

0.89 [0.78, 1.01]

1.1 Primary care trials

2

1008

Odds Ratio (M‐H, Random, 95% CI)

0.32 [0.01, 7.98]

1.2 Emergency department trials

14

3805

Odds Ratio (M‐H, Random, 95% CI)

0.97 [0.70, 1.36]

1.3 Intensive care unit trials

16

5233

Odds Ratio (M‐H, Random, 95% CI)

0.88 [0.77, 1.00]

2 Treatment failure at 30 days Show forest plot

32

10046

Odds Ratio (M‐H, Random, 95% CI)

0.90 [0.81, 0.99]

2.1 Primary care trials

2

1008

Odds Ratio (M‐H, Random, 95% CI)

0.94 [0.72, 1.22]

2.2 Emergency department trials

14

3805

Odds Ratio (M‐H, Random, 95% CI)

0.85 [0.69, 1.05]

2.3 Intensive care unit trials

16

5233

Odds Ratio (M‐H, Random, 95% CI)

0.92 [0.81, 1.05]

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Comparison 2. Procalcitonin algorithm versus no procalcitonin algorithm, sensitivity analyses

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mortality at 30 days stratified by adherence Show forest plot

32

10046

Odds Ratio (M‐H, Random, 95% CI)

0.89 [0.78, 1.01]

1.1 Adherence to procalcitonin algorithm > 70%

14

4422

Odds Ratio (M‐H, Random, 95% CI)

1.05 [0.81, 1.37]

1.2 Adherence to procalcitonin algorithm < 70% or not available

18

5624

Odds Ratio (M‐H, Random, 95% CI)

0.85 [0.73, 0.97]

2 Treatment failure at 30 days stratified by adherence Show forest plot

32

10046

Odds Ratio (M‐H, Random, 95% CI)

0.90 [0.81, 0.99]

2.1 Adherence to procalcitonin algorithm > 70%

14

4422

Odds Ratio (M‐H, Random, 95% CI)

0.87 [0.75, 1.02]

2.2 Adherence to procalcitonin algorithm < 70% or not available

18

5624

Odds Ratio (M‐H, Random, 95% CI)

0.92 [0.81, 1.04]

3 Mortality at 30 days stratified by allocation concealment Show forest plot

32

10046

Odds Ratio (M‐H, Random, 95% CI)

0.89 [0.78, 1.01]

3.1 Trials with concealed allocation

22

7968

Odds Ratio (M‐H, Random, 95% CI)

0.88 [0.76, 1.01]

3.2 Trials without concealed allocation

10

2078

Odds Ratio (M‐H, Random, 95% CI)

0.95 [0.70, 1.28]

4 Treatment failure at 30 days stratified by allocation concealment Show forest plot

32

10046

Odds Ratio (M‐H, Random, 95% CI)

0.90 [0.81, 0.99]

4.1 Trials with concealed allocation

22

7968

Odds Ratio (M‐H, Random, 95% CI)

0.91 [0.82, 1.02]

4.2 Trials without concealed allocation

10

2078

Odds Ratio (M‐H, Random, 95% CI)

0.82 [0.64, 1.04]

5 Mortality at 30 days stratified by blinded outcome assessment Show forest plot

32

10046

Odds Ratio (M‐H, Fixed, 95% CI)

0.89 [0.78, 1.00]

5.1 Trials with blinded outcome assessment

9

4664

Odds Ratio (M‐H, Fixed, 95% CI)

1.05 [0.84, 1.32]

5.2 Trials without blinded outcome assessment

23

5382

Odds Ratio (M‐H, Fixed, 95% CI)

0.82 [0.70, 0.95]

6 Treatment failure at 30 days stratified by blinded outcome assessment Show forest plot

32

10046

Odds Ratio (M‐H, Fixed, 95% CI)

0.90 [0.81, 0.99]

6.1 Trials with blinded outcome assessment

9

4664

Odds Ratio (M‐H, Fixed, 95% CI)

0.92 [0.79, 1.06]

6.2 Trials without blinded outcome assessment

23

5382

Odds Ratio (M‐H, Fixed, 95% CI)

0.88 [0.77, 1.01]

7 Mortality at 30 days stratified by follow up Show forest plot

32

10046

Odds Ratio (M‐H, Fixed, 95% CI)

0.89 [0.78, 1.00]

7.1 Trials with 1 month follow up for mortality

18

7337

Odds Ratio (M‐H, Fixed, 95% CI)

0.85 [0.74, 0.98]

7.2 Trials with different follow up for mortality

14

2709

Odds Ratio (M‐H, Fixed, 95% CI)

1.01 [0.78, 1.30]

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