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Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
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Figure 1

Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.

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Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
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Figure 2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study.

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QUOROM Diagram ‐ Search: until January 2009
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Figure 3

QUOROM Diagram ‐ Search: until January 2009

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Updated PRISMA diagram ‐ Search updated from Jan 2009 to February 2012
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Figure 4

Updated PRISMA diagram ‐ Search updated from Jan 2009 to February 2012

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Updated PRISMA diagram ‐ Search updated on 27 October 2014
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Figure 5

Updated PRISMA diagram ‐ Search updated on 27 October 2014

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Funnel plot of comparison: 1 Loop diuretics vs placebo, outcome: 1.1 SBP.
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Figure 6

Funnel plot of comparison: 1 Loop diuretics vs placebo, outcome: 1.1 SBP.

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Funnel plot of comparison: 1 Loop diuretics vs placebo, outcome: 1.2 DBP.
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Figure 7

Funnel plot of comparison: 1 Loop diuretics vs placebo, outcome: 1.2 DBP.

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Comparison 1 Loop diuretics vs placebo, Outcome 1 SBP.
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Analysis 1.1

Comparison 1 Loop diuretics vs placebo, Outcome 1 SBP.

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Comparison 1 Loop diuretics vs placebo, Outcome 2 DBP.
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Analysis 1.2

Comparison 1 Loop diuretics vs placebo, Outcome 2 DBP.

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Comparison 1 Loop diuretics vs placebo, Outcome 3 Withdrawals due to adverse events.
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Analysis 1.3

Comparison 1 Loop diuretics vs placebo, Outcome 3 Withdrawals due to adverse events.

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Comparison 1 Loop diuretics vs placebo, Outcome 4 Serum potassium.
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Analysis 1.4

Comparison 1 Loop diuretics vs placebo, Outcome 4 Serum potassium.

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Comparison 1 Loop diuretics vs placebo, Outcome 5 Serum uric acid.
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Analysis 1.5

Comparison 1 Loop diuretics vs placebo, Outcome 5 Serum uric acid.

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Comparison 1 Loop diuretics vs placebo, Outcome 6 Serum creatinine.
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Analysis 1.6

Comparison 1 Loop diuretics vs placebo, Outcome 6 Serum creatinine.

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Comparison 1 Loop diuretics vs placebo, Outcome 7 Blood glucose.
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Analysis 1.7

Comparison 1 Loop diuretics vs placebo, Outcome 7 Blood glucose.

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Comparison 1 Loop diuretics vs placebo, Outcome 8 serum cholesterol.
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Analysis 1.8

Comparison 1 Loop diuretics vs placebo, Outcome 8 serum cholesterol.

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Comparison 1 Loop diuretics vs placebo, Outcome 9 Serum triglyceride.
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Analysis 1.9

Comparison 1 Loop diuretics vs placebo, Outcome 9 Serum triglyceride.

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Loop diuretics compared with placebo for primary hypertension

Patient or population: People with primary hypertension

Settings: Outpatient

Intervention: Loop diuretics at various doses

Comparison: Placebo control

Outcomes

MD with (95% CI)

No. of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Decrease in SBP mmHg

mean duration 8.8 weeks

‐7.9(‐10.4 to ‐5.4)

460

(9)

⊕⊕⊝⊝
low1,2

Not significantly different from thiazides, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, or renin inhibitors.

Decrease in DBP mmHg

mean duration 8.8 weeks

‐4.4(‐5.9 to ‐2.8)

460

(9)

⊕⊕⊝⊝
low1,2

Not significantly different from thiazides, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, or renin inhibitors.

CI: confidence interval; MD: mean difference

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.

1. Wide confidence intervals

2. High risk of bias including publication bias
Figuras y tablas -
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Comparison 1. Loop diuretics vs placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 SBP Show forest plot

9

460

Mean Difference (IV, Fixed, 95% CI)

‐7.92 [‐10.40, ‐5.44]

1.1 Furosemide 40mg versus placebo

2

90

Mean Difference (IV, Fixed, 95% CI)

‐5.80 [‐12.96, 1.36]

1.2 Furosemide 60mg versus placebo

1

26

Mean Difference (IV, Fixed, 95% CI)

‐10.0 [‐15.77, ‐4.23]

1.3 Cicletanine 100mg versus placebo

1

39

Mean Difference (IV, Fixed, 95% CI)

‐7.0 [‐16.18, 2.18]

1.4 Cicletanine 150mg versus placebo

1

60

Mean Difference (IV, Fixed, 95% CI)

‐9.10 [‐15.54, ‐2.66]

1.5 Piretanide 3mg versus placebo

1

60

Mean Difference (IV, Fixed, 95% CI)

‐2.2 [‐9.97, 5.57]

1.6 Piretanide 6mg versus placebo

2

120

Mean Difference (IV, Fixed, 95% CI)

‐4.65 [‐10.01, 0.71]

1.7 Indacrinone enantiomer ‐2.5 /+ 80mg versus placebo

1

12

Mean Difference (IV, Fixed, 95% CI)

‐14.90 [‐31.15, 1.35]

1.8 Indacrinone ‐5.0 /+ 80mg versus placebo

1

12

Mean Difference (IV, Fixed, 95% CI)

‐11.70 [‐25.37, 1.97]

1.9 Indacrinone ‐10.0 /+ 80 mg versus placebo

1

13

Mean Difference (IV, Fixed, 95% CI)

‐19.1 [‐35.95, ‐2.25]

1.10 Etozolin 200mg versus placebo

1

28

Mean Difference (IV, Fixed, 95% CI)

‐14.30 [‐23.05, ‐5.55]

2 DBP Show forest plot

9

460

Mean Difference (IV, Fixed, 95% CI)

‐4.36 [‐5.87, ‐2.84]

2.1 Furosemide 40mg versus placebo

2

90

Mean Difference (IV, Fixed, 95% CI)

‐3.53 [‐7.28, 0.23]

2.2 Furosemide 60mg versus placebo

1

26

Mean Difference (IV, Fixed, 95% CI)

‐3.00 [‐7.26, 1.26]

2.3 Cicletanine 100mg versus placebo

1

39

Mean Difference (IV, Fixed, 95% CI)

‐3.30 [‐9.48, 2.88]

2.4 Cicletanine 150mg versus placebo

1

60

Mean Difference (IV, Fixed, 95% CI)

‐11.3 [‐15.30, ‐7.30]

2.5 Piretanide 3mg versus placebo

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.80 [‐5.44, 3.84]

2.6 Piretanide 6mg versus placebo

2

120

Mean Difference (IV, Fixed, 95% CI)

‐2.32 [‐5.48, 0.84]

2.7 Indacrinone enantiomer ‐2.5 /+ 80mg versus placebo

1

12

Mean Difference (IV, Fixed, 95% CI)

‐7.1 [‐15.16, 0.96]

2.8 Indacrinone ‐5.0 /+ 80mg versus placebo

1

12

Mean Difference (IV, Fixed, 95% CI)

‐3.40 [‐11.24, 4.44]

2.9 Indacrinone ‐10.0 /+ 80 mg versus placebo

1

13

Mean Difference (IV, Fixed, 95% CI)

‐3.40 [‐11.61, 4.81]

2.10 Etozolin 200mg versus placebo

1

28

Mean Difference (IV, Fixed, 95% CI)

‐7.30 [‐13.22, ‐1.38]

3 Withdrawals due to adverse events Show forest plot

6

331

Risk Ratio (M‐H, Fixed, 95% CI)

1.93 [0.34, 10.81]

4 Serum potassium Show forest plot

2

88

Mean Difference (IV, Fixed, 95% CI)

‐0.12 [‐0.36, 0.12]

4.1 Cicletanine 150mg

1

58

Mean Difference (IV, Fixed, 95% CI)

‐0.12 [‐0.36, 0.12]

4.2 Furosemide 40mg

1

30

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

5 Serum uric acid Show forest plot

2

88

Mean Difference (IV, Fixed, 95% CI)

10.52 [‐17.88, 38.92]

5.1 Cicletanine 150mg

1

58

Mean Difference (IV, Fixed, 95% CI)

‐7.0 [‐40.75, 26.75]

5.2 Furosemide 40mg

1

30

Mean Difference (IV, Fixed, 95% CI)

53.00 [0.44, 105.56]

6 Serum creatinine Show forest plot

2

88

Mean Difference (IV, Fixed, 95% CI)

0.93 [‐5.74, 7.61]

6.1 Cicletanine 150mg

1

58

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐9.63, 8.23]

6.2 Furosemide 40 mg

1

30

Mean Difference (IV, Fixed, 95% CI)

3.0 [‐7.05, 13.05]

7 Blood glucose Show forest plot

2

88

Mean Difference (IV, Fixed, 95% CI)

0.06 [‐0.19, 0.31]

7.1 Cicletanine 150mg

1

58

Mean Difference (IV, Fixed, 95% CI)

‐0.01 [‐0.40, 0.38]

7.2 Furosemide 40mg

1

30

Mean Difference (IV, Fixed, 95% CI)

0.1 [‐0.22, 0.42]

8 serum cholesterol Show forest plot

2

88

Mean Difference (IV, Fixed, 95% CI)

0.31 [‐0.17, 0.80]

8.1 Cicletanine 150mg

1

58

Mean Difference (IV, Fixed, 95% CI)

0.17 [‐0.51, 0.85]

8.2 Furosemide 40 mg

1

30

Mean Difference (IV, Fixed, 95% CI)

0.46 [‐0.23, 1.15]

9 Serum triglyceride Show forest plot

2

88

Mean Difference (IV, Fixed, 95% CI)

‐0.02 [‐0.35, 0.31]

9.1 Cicletanine 150mg

1

58

Mean Difference (IV, Fixed, 95% CI)

‐0.16 [‐0.54, 0.22]

9.2 Furosemide 40 mg

1

30

Mean Difference (IV, Fixed, 95% CI)

0.36 [‐0.27, 0.99]
Figuras y tablas -
Comparison 1. Loop diuretics vs placebo
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