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Primary outcome funnel plot
Figuras y tablas -
Figure 1

Primary outcome funnel plot

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Number needed to treat with LABA rather than LRTA in addition to ICS to prevent one patient having one or more exacerbations over 48 weeks
Figuras y tablas -
Figure 2

Number needed to treat with LABA rather than LRTA in addition to ICS to prevent one patient having one or more exacerbations over 48 weeks

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 1 Participants with one or more exacerbations requiring systemic corticosteroids.
Figuras y tablas -
Analysis 1.1

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 1 Participants with one or more exacerbations requiring systemic corticosteroids.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 2 Morning PEF (L/min) ‐ change from baseline.
Figuras y tablas -
Analysis 1.2

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 2 Morning PEF (L/min) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 3 Evening PEF (L/min) ‐ change from baseline.
Figuras y tablas -
Analysis 1.3

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 3 Evening PEF (L/min) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 4 FEV1 (L) ‐ change from baseline.
Figuras y tablas -
Analysis 1.4

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 4 FEV1 (L) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 5 FEV1 (L) ‐ % change from baseline.
Figuras y tablas -
Analysis 1.5

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 5 FEV1 (L) ‐ % change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 6 FEV1 (% predicted) ‐ end of treatment.
Figuras y tablas -
Analysis 1.6

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 6 FEV1 (% predicted) ‐ end of treatment.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 7 % fall in FEV1 POST‐EXERCISE.
Figuras y tablas -
Analysis 1.7

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 7 % fall in FEV1 POST‐EXERCISE.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 8 Rescue‐free days (%) ‐ change from baseline.
Figuras y tablas -
Analysis 1.8

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 8 Rescue‐free days (%) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 9 Rescue medication use (puffs/day) ‐ change from baseline.
Figuras y tablas -
Analysis 1.9

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 9 Rescue medication use (puffs/day) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 10 Change in Global asthma QoL AQLQ Score (higher is better) ‐ change from baseline.
Figuras y tablas -
Analysis 1.10

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 10 Change in Global asthma QoL AQLQ Score (higher is better) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 11 Symptom free days (%) ‐ change from baseline.
Figuras y tablas -
Analysis 1.11

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 11 Symptom free days (%) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 12 Night‐time symptom score (5pt scale, higher score is worse) ‐ change from baseline.
Figuras y tablas -
Analysis 1.12

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 12 Night‐time symptom score (5pt scale, higher score is worse) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 13 Day‐time symptom scores (high is worse) ‐ change from baseline.
Figuras y tablas -
Analysis 1.13

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 13 Day‐time symptom scores (high is worse) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 14 Morning symptoms ‐ change from baseline.
Figuras y tablas -
Analysis 1.14

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 14 Morning symptoms ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 15 Change in number of night awakenings per week ‐ change from baseline.
Figuras y tablas -
Analysis 1.15

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 15 Change in number of night awakenings per week ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 16 Change in % of nights with no awakenings per week ‐ change from baseline.
Figuras y tablas -
Analysis 1.16

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 16 Change in % of nights with no awakenings per week ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 17 Rescue‐free nights (%) ‐ change from baseline.
Figuras y tablas -
Analysis 1.17

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 17 Rescue‐free nights (%) ‐ change from baseline.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 18 Withdrawals for any reason.
Figuras y tablas -
Analysis 1.18

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 18 Withdrawals for any reason.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 19 Withdrawals due to adverse events.
Figuras y tablas -
Analysis 1.19

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 19 Withdrawals due to adverse events.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 20 Withdrawals due to poor asthma control/asthma exacerbation.
Figuras y tablas -
Analysis 1.20

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 20 Withdrawals due to poor asthma control/asthma exacerbation.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 21 Patients with one or more exacerbations requiring hospital admission.
Figuras y tablas -
Analysis 1.21

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 21 Patients with one or more exacerbations requiring hospital admission.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 22 Serious Adverse events.
Figuras y tablas -
Analysis 1.22

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 22 Serious Adverse events.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 23 Death.
Figuras y tablas -
Analysis 1.23

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 23 Death.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 24 Headache.
Figuras y tablas -
Analysis 1.24

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 24 Headache.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 25 Cardiovascular events.
Figuras y tablas -
Analysis 1.25

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 25 Cardiovascular events.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 26 Oral moniliasis.
Figuras y tablas -
Analysis 1.26

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 26 Oral moniliasis.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 27 Osteopenia/osteoporosis.
Figuras y tablas -
Analysis 1.27

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 27 Osteopenia/osteoporosis.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 28 Elevated liver enzymes.
Figuras y tablas -
Analysis 1.28

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 28 Elevated liver enzymes.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 29 Overall adverse events.
Figuras y tablas -
Analysis 1.29

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 29 Overall adverse events.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 30 Patient treatment satisfaction.
Figuras y tablas -
Analysis 1.30

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 30 Patient treatment satisfaction.

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Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 31 Change from baseline in serum eosinophils ( x 10e9/L).
Figuras y tablas -
Analysis 1.31

Comparison 1 Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS, Outcome 31 Change from baseline in serum eosinophils ( x 10e9/L).

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Comparison 2 LABA + ICS vs LTRA + ICS (subgroup analyses), Outcome 1 PRIMARY OUTCOME: Subgroup analysis (Separate inhalers vs. Single inhaler use for delivery of LABA+ICS).
Figuras y tablas -
Analysis 2.1

Comparison 2 LABA + ICS vs LTRA + ICS (subgroup analyses), Outcome 1 PRIMARY OUTCOME: Subgroup analysis (Separate inhalers vs. Single inhaler use for delivery of LABA+ICS).

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Comparison 2 LABA + ICS vs LTRA + ICS (subgroup analyses), Outcome 2 Serious adverse effects stratified by # devices used for LABA + ICS.
Figuras y tablas -
Analysis 2.2

Comparison 2 LABA + ICS vs LTRA + ICS (subgroup analyses), Outcome 2 Serious adverse effects stratified by # devices used for LABA + ICS.

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Table 1. Search history

Years

Detail

All years to January 2004

Citations: 184 (181 from the literature search and three unpublished trials provided by pharmaceutical companies for a total of 184 citations)

Citations excluded: 172: (1) duplicate citations (N=29), (2) abstracts of considered full‐text publications or secondary analyses of the same study (N = 18), (3) not a randomised controlled trial (N = 72), (4) protocol of ongoing trial (N=1), (5) no consistent co‐treatment with inhaled glucocorticoids (N = 21), (6) one of the tested interventions was not daily LTRA (N = 18), (7) one of the tested interventions was not daily LABA (N= 5), (8) interventions were administered for less than 4 weeks (N = 6), and (9) use of prohibited co‐interventions such as LABA in both groups (N=2).

Studies meeting the entry criteria of the review: 12 (six full‐text publications (Bjermer 2003; Fish 2001; Ilowite 2004; Nelson 2000; Nelson 2001; Ringdal 2003), two unpublished full‐text reports (Hultquist 2000; McCarthy 2003) and four abstracts (Gold (abs) 2001; Green (abs) 2002; Leibman (abs) 2002; Nsouli 2001). The abstracts did not provide data in sufficient detail to contribute to the meta‐analyses.

Figuras y tablas -
Table 1. Search history
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Comparison 1. Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Participants with one or more exacerbations requiring systemic corticosteroids Show forest plot

6

5571

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.71, 0.97]

1.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

5

5142

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.71, 0.97]

1.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.29, 2.52]

2 Morning PEF (L/min) ‐ change from baseline Show forest plot

10

5669

Mean Difference (IV, Fixed, 95% CI)

15.66 [13.21, 18.11]

2.1 Montelukast 10 mg once daily versus salmeterol 50 mcg twice daily

7

4968

Mean Difference (IV, Fixed, 95% CI)

15.59 [12.93, 18.26]

2.2 Zafirlukast 20 mg twice daily versus salmeterol 50 mcg or formoterol 9 mg twice daily

2

661

Mean Difference (IV, Fixed, 95% CI)

13.70 [6.65, 20.75]

2.3 Montelukast 10 mg once daily versus formoterol 18mg twice daily

1

40

Mean Difference (IV, Fixed, 95% CI)

23.80 [10.89, 36.71]

3 Evening PEF (L/min) ‐ change from baseline Show forest plot

9

3958

Mean Difference (IV, Fixed, 95% CI)

12.09 [9.26, 14.92]

3.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

6

3259

Mean Difference (IV, Fixed, 95% CI)

12.40 [9.24, 15.57]

3.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg or Formoterol 9 mg twice daily

2

659

Mean Difference (IV, Fixed, 95% CI)

9.35 [2.33, 16.37]

3.3 Montelukast 10 mg once daily versus formoterol 18mg twice daily

1

40

Mean Difference (IV, Fixed, 95% CI)

17.5 [2.81, 32.19]

4 FEV1 (L) ‐ change from baseline Show forest plot

8

4485

Mean Difference (IV, Fixed, 95% CI)

0.08 [0.06, 0.10]

4.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

5

3783

Mean Difference (IV, Fixed, 95% CI)

0.08 [0.06, 0.11]

4.2 Zafirlukast 20mg twice daily vs. Salmeterol 50 mcg or Formoterol 9mcg twice daily

2

662

Mean Difference (IV, Fixed, 95% CI)

0.05 [‐0.02, 0.12]

4.3 Montelukast 10 mg once daily versus formoterol 18mg twice daily

1

40

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 FEV1 (L) ‐ % change from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

5.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.2 Zafirlukast 20mg twice daily vs. Salmeterol 50 mcg or Formoterol 9mcg twice daily

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 FEV1 (% predicted) ‐ end of treatment Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

6.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.2 Zafirlukast 20mg twice daily vs. Salmeterol 50 mcg or Formoterol 9mcg twice daily

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

7 % fall in FEV1 POST‐EXERCISE Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

7.1 Montelukast 10 mg once daily versus salmeterol 50 mcg twice daily

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

7.2 Zafirlukast 20mg twice daily versus.salmeterol 50 mcg or formoterol 9mcg twice daily

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

8 Rescue‐free days (%) ‐ change from baseline Show forest plot

5

2612

Mean Difference (IV, Random, 95% CI)

9.18 [5.39, 12.98]

8.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

4

2183

Mean Difference (IV, Random, 95% CI)

7.33 [4.41, 10.26]

8.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Mean Difference (IV, Random, 95% CI)

15.0 [9.43, 20.57]

9 Rescue medication use (puffs/day) ‐ change from baseline Show forest plot

7

4055

Mean Difference (IV, Random, 95% CI)

‐0.49 [‐0.75, ‐0.24]

9.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

4

3353

Mean Difference (IV, Random, 95% CI)

‐0.37 [‐0.56, ‐0.19]

9.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg or Formoterol 9 mg twice daily

2

662

Mean Difference (IV, Random, 95% CI)

‐0.36 [‐0.72, 0.00]

9.3 Montelukast 10 mg once daily versus formoterol 18mg twice daily

1

40

Mean Difference (IV, Random, 95% CI)

‐1.4 [‐1.81, ‐0.99]

10 Change in Global asthma QoL AQLQ Score (higher is better) ‐ change from baseline Show forest plot

3

2893

Mean Difference (IV, Fixed, 95% CI)

0.11 [0.05, 0.17]

10.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

2

2464

Mean Difference (IV, Fixed, 95% CI)

0.09 [0.03, 0.16]

10.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Mean Difference (IV, Fixed, 95% CI)

0.19 [0.02, 0.36]

11 Symptom free days (%) ‐ change from baseline Show forest plot

5

2626

Mean Difference (IV, Random, 95% CI)

6.75 [3.11, 10.39]

11.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

4

2197

Mean Difference (IV, Random, 95% CI)

5.42 [1.80, 9.05]

11.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Mean Difference (IV, Random, 95% CI)

11.0 [6.10, 15.90]

12 Night‐time symptom score (5pt scale, higher score is worse) ‐ change from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

12.1 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

13 Day‐time symptom scores (high is worse) ‐ change from baseline Show forest plot

5

3823

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.18 [‐0.25, ‐0.12]

13.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

4

3394

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.17 [‐0.24, ‐0.10]

13.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Std. Mean Difference (IV, Fixed, 95% CI)

‐0.29 [‐0.48, ‐0.10]

14 Morning symptoms ‐ change from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

14.1 Montelukast 10 mg once daily versus formoterol 18mg twice daily

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

15 Change in number of night awakenings per week ‐ change from baseline Show forest plot

4

4214

Mean Difference (IV, Fixed, 95% CI)

‐0.12 [‐0.19, ‐0.06]

15.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

3

3785

Mean Difference (IV, Fixed, 95% CI)

‐0.16 [‐0.26, ‐0.05]

15.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Mean Difference (IV, Fixed, 95% CI)

‐0.1 [‐0.18, ‐0.02]

16 Change in % of nights with no awakenings per week ‐ change from baseline Show forest plot

2

673

Mean Difference (IV, Fixed, 95% CI)

6.89 [2.87, 10.91]

16.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

1

244

Mean Difference (IV, Fixed, 95% CI)

6.60 [‐1.06, 14.26]

16.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Mean Difference (IV, Fixed, 95% CI)

7.0 [2.28, 11.72]

17 Rescue‐free nights (%) ‐ change from baseline Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Totals not selected

17.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

1

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

17.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

18 Withdrawals for any reason Show forest plot

10

6225

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.73, 0.95]

18.1 Montelukast 10mg/day vs Salmeterol 50ug twice daily

8

5560

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.74, 0.97]

18.2 Zafirlukast 20 mg twice daily vs Salmeterol 50 mcg twice daily

2

665

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.40, 1.06]

19 Withdrawals due to adverse events Show forest plot

10

6225

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.80, 1.32]

19.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

8

5560

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.79, 1.35]

19.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

2

665

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.41, 2.05]

20 Withdrawals due to poor asthma control/asthma exacerbation Show forest plot

8

5354

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.49, 1.56]

20.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

6

4689

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.50, 2.07]

20.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

2

665

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.19, 1.32]

21 Patients with one or more exacerbations requiring hospital admission Show forest plot

4

3993

Risk Ratio (M‐H, Fixed, 95% CI)

1.31 [0.58, 2.98]

21.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

4

3993

Risk Ratio (M‐H, Fixed, 95% CI)

1.31 [0.58, 2.98]

22 Serious Adverse events Show forest plot

6

5592

Risk Ratio (M‐H, Fixed, 95% CI)

1.32 [0.98, 1.79]

22.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

5

5163

Risk Ratio (M‐H, Fixed, 95% CI)

1.32 [0.98, 1.79]

22.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.06, 15.96]

23 Death Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

23.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

2

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

24 Headache Show forest plot

10

6187

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.90, 1.26]

24.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

7

5482

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.92, 1.29]

24.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

2

665

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.36, 1.57]

24.3 Montelukast 10 mg once daily versus formoterol 18mg twice daily

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.07, 14.90]

25 Cardiovascular events Show forest plot

5

5163

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.77, 1.53]

25.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

5

5163

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.77, 1.53]

26 Oral moniliasis Show forest plot

6

5203

Risk Ratio (M‐H, Fixed, 95% CI)

1.86 [1.00, 3.44]

26.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

5

5163

Risk Ratio (M‐H, Fixed, 95% CI)

1.92 [1.02, 3.61]

26.2 Montelukast 10 mg once daily versus formoterol 18mg twice daily

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.07, 14.90]

27 Osteopenia/osteoporosis Show forest plot

2

2963

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.12, 2.63]

27.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

2

2963

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.12, 2.63]

28 Elevated liver enzymes Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Totals not selected

28.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

1

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

29 Overall adverse events Show forest plot

8

5911

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.99, 1.07]

29.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

7

5482

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.99, 1.07]

29.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.81, 1.31]

30 Patient treatment satisfaction Show forest plot

3

2020

Risk Ratio (M‐H, Random, 95% CI)

1.12 [1.04, 1.20]

30.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

2

1591

Risk Ratio (M‐H, Random, 95% CI)

1.09 [1.05, 1.14]

30.2 Zafirlukast 20 mg twice daily vs. Salmeterol 50 mcg twice daily

1

429

Risk Ratio (M‐H, Random, 95% CI)

1.27 [1.10, 1.47]

31 Change from baseline in serum eosinophils ( x 10e9/L) Show forest plot

2

2787

Mean Difference (IV, Fixed, 95% CI)

0.04 [0.02, 0.05]

31.1 Montelukast 10 mg once daily vs. Salmeterol 50 mcg twice daily

2

2787

Mean Difference (IV, Fixed, 95% CI)

0.04 [0.02, 0.05]
Figuras y tablas -
Comparison 1. Leukotriene receptor antagonists + ICS versus Long‐acting ß2‐agonists + ICS
Ir a la tabla de la revisión
Comparison 2. LABA + ICS vs LTRA + ICS (subgroup analyses)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 PRIMARY OUTCOME: Subgroup analysis (Separate inhalers vs. Single inhaler use for delivery of LABA+ICS) Show forest plot

6

5571

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.71, 0.97]

1.1 Montelukast 10mg od or Zafirlukast 20mg bd vs. Salmeterol 50mcg bd ‐ SEPARATE INHALERS USED

4

4319

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.75, 1.04]

1.2 Montelukast 10mg od vs. Salmeterol 50mcg bd ‐ SINGLE INHALER USED

2

1252

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.29, 0.82]

2 Serious adverse effects stratified by # devices used for LABA + ICS Show forest plot

6

5592

Risk Ratio (M‐H, Fixed, 95% CI)

1.32 [0.98, 1.79]

2.1 1 device for LABA + ICS

2

1252

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.19, 1.64]

2.2 2 devices for LABA + ICS

4

4340

Risk Ratio (M‐H, Fixed, 95% CI)

1.43 [1.04, 1.97]
Figuras y tablas -
Comparison 2. LABA + ICS vs LTRA + ICS (subgroup analyses)
Ir a la tabla de la revisión