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Statins for acute coronary syndrome
Noah Vale, Alain J Nordmann, Gregory G Schwartz, James de Lemos, Furio Colivicchi, Frank den Hartog, Petr Ostadal, Stella M Macin, Anho H Liem, Edward J Mills, Neera Bhatnagar, Heiner C Bucher, Matthias Briel | 1 September 2014

Cochrane Clinical Answers

Topics

Topics

Study flow diagram
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Figure 1

Study flow diagram

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Risk of bias summary: review authors' judgements about each risk of bias item for each included study
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Figure 2

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

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Meta‐regression by duration of treatment using the 'matreg' command in Stata version 13 (stata.com) (Number of observations: 12, P = 0.15)
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Figure 3

Meta‐regression by duration of treatment using the 'matreg' command in Stata version 13 (stata.com) (Number of observations: 12, P = 0.15)

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Meta‐regression by proportion of participants with prior myocardial infarction using the 'matreg' command in Stata version 13 (stata.com) (Number of observations:8, P = 0.19)
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Figure 4

Meta‐regression by proportion of participants with prior myocardial infarction using the 'matreg' command in Stata version 13 (stata.com) (Number of observations:8, P = 0.19)

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Meta‐regression by proportion of participants receiving background statin therapy using the 'matreg' command in Stata version 13 (stata.com) (Number of observations: 10, P = 0.15)
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Figure 5

Meta‐regression by proportion of participants receiving background statin therapy using the 'matreg' command in Stata version 13 (stata.com) (Number of observations: 10, P = 0.15)

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Funnel plot of comparison: 1 niacin over placebo, maximum follow‐up, available case analysis, outcome: 1.1 overall mortality
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Figure 6

Funnel plot of comparison: 1 niacin over placebo, maximum follow‐up, available case analysis, outcome: 1.1 overall mortality

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 1 Overall mortality.
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Analysis 1.1

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 1 Overall mortality.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 2 Overall mortality, sensitivity analysis with stratification by risk of bias trials only.
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Analysis 1.2

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 2 Overall mortality, sensitivity analysis with stratification by risk of bias trials only.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 3 Fatal myocardial infarction.
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Analysis 1.3

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 3 Fatal myocardial infarction.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 4 Cardiovascular mortality.
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Analysis 1.4

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 4 Cardiovascular mortality.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 5 Non‐cardiovascular mortality.
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Analysis 1.5

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 5 Non‐cardiovascular mortality.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 6 Non‐fatal myocardial infarction.
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Analysis 1.6

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 6 Non‐fatal myocardial infarction.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 7 Fatal or non‐fatal myocardial infarction.
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Analysis 1.7

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 7 Fatal or non‐fatal myocardial infarction.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 8 Fatal and non‐fatal stroke.
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Analysis 1.8

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 8 Fatal and non‐fatal stroke.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 9 Revascularisation procedures.
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Analysis 1.9

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 9 Revascularisation procedures.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 10 Flushing.
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Analysis 1.10

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 10 Flushing.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 11 Pruritus.
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Analysis 1.11

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 11 Pruritus.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 12 Rash.
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Analysis 1.12

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 12 Rash.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 13 Headache.
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Analysis 1.13

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 13 Headache.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 14 Gastrointestinal symptoms.
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Analysis 1.14

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 14 Gastrointestinal symptoms.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 15 Discontinuation of treatment due to side effects.
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Analysis 1.15

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 15 Discontinuation of treatment due to side effects.

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Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 16 New onset diabetes).
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Analysis 1.16

Comparison 1 Niacin versus control, maximum follow‐up, available case analysis, Outcome 16 New onset diabetes).

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Summary of findings for the main comparison. Niacin for primary and secondary prevention of cardiovascular events

Niacin for primary and secondary prevention of cardiovascular events

Patient or population: people with or at risk of cardiovascular disease
Setting: secondary care and tertiary care
Intervention: niacin monotherapy or add‐on
Comparison: placebo or usual care

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with placebo

Risk with niacin

Overall mortality
(follow‐up: 0.5 years to 5 years)

Study population

RR 1.05
(0.97 to 1.12)

35,543
(12 RCTs)

⊕⊕⊕⊕
High

High‐quality evidence that niacin does not reduce overall mortality (CI excludes clinically important benefit)

86 per 1000

90 per 1000
(83 to 96)

Cardiovascular mortality

(follow‐up: 1 year to 5 years)

Study population

RR 1.02
(0.93 to 1.12)

32,966
(5 RCTs)

⊕⊕⊕⊝
Moderate1

Moderate‐quality evidence that niacin does not reduce cardiovascular mortality

63 per 1000

64 per 1000
(58 to 70)

Non‐cardiovascular mortality

(follow‐up: 1 year to 5 years)

Study population

RR 1.12
(0.98 to 1.28)

32,966
(5 RCTs)

⊕⊕⊕⊕
High

High‐quality evidence that niacin does not reduce non‐cardiovascular mortality (CI excludes clinically important benefit)

24 per 1000

27 per 1000
(24 to 31)

Fatal or non‐fatal myocardial infarction

(follow up: 0.5 years to 5 years)

Study population

RR 0.93
(0.87 to 1.00)

34,829
(9 RCTs)

⊕⊕⊕⊝
Moderate1

Moderate‐quality evidence that niacin does not reduce the number of fatal and non‐fatal myocardial infarctions

95 per 1000

90 per 1000
(83 to 95)

Fatal and non‐fatal stroke

(follow‐up: 0.5 years to 5 years)

Study population

RR 0.95
(0.74 to 1.22)

33,661
(7 RCTs)

⊕⊕⊝⊝
Low1,2

Low‐quality evidence that niacin does not reduce the number of strokes

47 per 1000

45 per 1000
(35 to 59)

Discontinuation of treatment due to side effects

(follow‐up: 0.5 years to 4 years)

Study population

RR 2.17
(1.70 to 2.77)

33,539
(17 RCTs)

⊕⊕⊕⊝
Moderate2

Moderate‐quality evidence that niacin does increase the number of participants discontinuing treatment due to side effects

91 per 1000

210 per 1000
(162 to 273)

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

CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

1Confidence interval includes clinically relevant benefit and no benefit. We downgraded by one level due to imprecision.
2High heterogeneity in point estimates. We downgraded by one level due to inconsistency.

Figures and Tables -
Summary of findings for the main comparison. Niacin for primary and secondary prevention of cardiovascular events
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Table 1. Sensitivity analysis assuming different relationship between the outcomes from observed and missing participants

Outcome

Available case analysis

IMOR 1.0, 1.0*

IMOR 0.5, 2.0*

IMOR 2.0, 0.5*

RR (95% CI)

I2

RR (95% CI)

I2

RR (95% CI)

I2

RR (95% CI)

I2

Overall mortality

1.05 (0.97 to 1.12)

0%

1.05 (0.97 to 1.12)

0%

1.04 (0.96 to 1.11)

0%

1.06 (0.98 to 1.14)

0%

Cardiovascular mortality

1.02 (0.93 to 1.12)

0%

1.02 (0.93 to 1.12)

0%

1.01 (0.92 to 1.11)

0%

1.03 (0.94 to 1.13)

0%

Non‐cardiovascular mortality

1.12 (0.98 to 1.28)

0%

1.12 (0.98 to 1.28)

0%

1.11 (0.97 to 1.27)

0%

1.14 (1.00 to 1.30)

0%

Fatal or non‐fatal myocardial infarction

0.93 (0.87 to 1.00)

0%

0.93 (0.87 to 1.00)

0%

0.92 (0.86 to 0.99)

0%

0.96 (0.87 to 1.05)

14%

Fatal myocardial infarction

1.01 (0.91 to 1.11)

0%

1.01 (0.91 to 1.11)

0%

1.00 (0.90 to 1.10)

0%

1.02 (0.92 to 1.12)

0%

Non‐fatal myocardial infarction

0.91 (0.77 to 1.07)

53%

0.91 (0.77 to 1.07)

53%

0.89 (0.76 to 1.05)

47%

0.92 (0.77 to 1.10)

57%

Fatal or non‐fatal stroke

0.95 (0.74 to 1.22)

42%

0.95 (0.74 to 1.22)

42%

0.94 (0.73 to 1.21)

42%

0.97 (0.75 to 1.26)

42%

Revascularisation

0.85 (0.68 to 1.06)

45%

0.85 (0.68 to 1.06)

45%

0.83 (0.66 to 1.04)

48%

0.88 (0.69 to 1.09)

47%

Discontinuation of treatment due to side effects

2.16 (1.70 to 2.76)

77%

2.15 (1.68 to 2.74)

75%

1.96 (1.55 to 2.49)

73%

2.35 (1.82 to 3.03)

77%

Flushing

7.69 (4.15 to 14.26)

91%

7.66 (4.11 to 14.29)

91%

6.68 (3.54 to 12.58)

91%

8.61 (4.67 to 15.87)

90%

Rash

3.16 (1.96 to 5.12)

52%

3.14 (1.93 to 5.10)

51%

2.74 (1.80 to 4.19)

40%

3.69 (2.13 to 6.40)

60%

Pruritus

5.15 (2.62 to 10.13)

67%

5.21 (2.68 to 10.13)

62%

4.23 (1.94 to 9.23)

72%

6.48 (3.78 to 11.10)

46%

Gastrointestinal symptoms

1.69 (1.37 to 2.09)

62%

1.69 (1.36 to 2.11)

60%

1.53 (1.23 to 1.91)

59%

1.88 (1.48 to 2.39)

66%

Headache

1.41 (0.86 to 2.30)

0%

1.43 (0.83 to 2.46)

0%

1.14 (0.64 to 2.03)

0%

1.76 (1.05 to 2.97)

0%

CI: confidence interval; IMOR: informative missingness odds ratio; RR: risk ratio

Sensitivity analysis for random‐effects meta‐analysis assuming different relationship between the outcomes from observed and missing participants and accounting for the uncertainty introduced by the proportion of missing data and assumed relationship (informative missingness odds ratio, IMOR = odds of event in missing data/odds of event in observed data, SD(logIMOR) = 0.5). We used the “metamiss”‐command in Stata (version 13) (stata.com).

*The two numbers represent the assumed IMORs for the niacin and the control arm, respectively: 1.0, 1.0: missing at random; 0.5, 2.0: assumption favours niacin, 2.0, 0.5: assumption favours control.

We could not conduct sensitivity analysis for the outcome 'new onset diabetes' because the proportion of missing data was not reported.

Figures and Tables -
Table 1. Sensitivity analysis assuming different relationship between the outcomes from observed and missing participants
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Table 2. Lipid data

Study

Niacin dose g/day

Follow‐up in months

Total cholesterol

LDL‐cholesterol

HDL‐cholesterol

Triglycerides

Baseline mean,
(treatment effect: difference between niacin and control group in mean change from baseline) in mg/dL

ADMIT 2000

3

11

214 (‐4)

138 (‐6)

41 (+11)

176 (‐34)

AIM‐HIGH 2011

2

38

NA (NA)

74 (‐3)

35 (+10)

165 (‐21)

ALPINE‐SVG 2015

2

12

136 (+1)

69 (+2)

38 (+3)

158 (‐19)

ARBITER‐2 2004

1

12

158 (+6)

89 (+3)

40 (+8)

163 (‐12)

Capuzzi 2003

2

6

262 (+3)

146 (+6)

36 (+6)

377 (‐6)

Carotid IMT 2008

2

18

237 (‐6)

154 (‐9)

42 (+6)

201 (‐16)

CDP 1975

3

72

249 (‐20)

NA (NA)

NA (NA)

NA (NA)

Goldberg 2000

3

6

300 (‐31)

216 (‐48)

45 (+8)

191 (NA)

Guyton 2008

2

6

241 (‐4)

156 (‐9)

51 (+11)

159 (‐30)

Harikrishnan 2008

1.5

9

178 (‐9)

112 (‐11)

35 (+5)

157 (‐5)

Heart positive 2011

2

6

211 (‐7)

NA (NA)

39 (+5)

306 (‐25)

HPS2‐THRIVE 2014

2

23

128 (‐5)

63 (‐10)

43 (+6)

124 (‐33)

Hunninghake 2003

2

6

NA (NA)

188 (‐10)

44 (+24)

197 (‐23)

Lee 2009

2

12

157 (+1)

85 (‐15)

38 (+22)

180 (‐7)

Lee 2011

1

9

198 (NA)

122 (NA)

49 (NA)

160 (NA)

Linke 2009

1

6

218 (+4)

133 (‐9)

33 (+5)

154 (‐29)

Maccubbin 2008

2

6

192 (‐9)

223 (‐20)

52 (+22)

122 (‐57)

MacLean 2011

2

8

127 (NA)

164 (‐33)

86 (+21)

50 (‐15)

Nash 2011

2

12

178 (‐15)

118 (‐22)

33 (+8)

141 (‐21)

NIA Plaque 2013

1.5

18

172 (0)

90 (‐4)

60 (+8)

130 (‐26)

PAST 1995

0.5

36

243 (‐8)

169 (‐13)

42 (+1)

162 (‐25)

Sang 2009

1

12

183 (NA)

105 (NA)

50 (NA)

147 (NA)

Schoch 1968

4

38

242 (‐34)

NA (NA)

NA (NA)

NA (NA)

NA: not available

Figures and Tables -
Table 2. Lipid data
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Table 3. Number randomised, complete, missing, and events

Study

Outcome

Niacin group

Control group

Randomised

Complete

Missing

Events

Randomised

Complete

Missing

Events

ADMIT 2000

Discontinuation of treatment due to side effects

237

213

24

19

231

209

22

9

AIM‐HIGH 2011

Fatal myocardial infarction

1718

1693

25

38

1696

1672

24

34

Non‐cardiovascular mortality

1718

1693

25

51

1696

1672

24

44

Fatal or non‐fatal myocardial infarction

1718

1693

25

112

1696

1672

24

106

Cardiovascular mortality

1718

1693

25

45

1696

1672

24

38

Overall mortality

1718

1693

25

96

1696

1672

24

82

Non‐fatal myocardial infarction

1718

1693

25

104

1696

1672

24

93

Revascularisation procedures

1718

1693

25

167

1696

1672

24

168

Fatal or non‐fatal stroke

1718

1693

25

30

1696

1672

24

18

Flushing

1718

1693

25

104

1696

1672

24

43

Gastrointestinal symptoms

1718

1693

25

26

1696

1672

24

12

Discontinuation of treatment due to side effects

1718

1693

25

436

1696

1672

24

341

ARBITER‐2 2004

Flushing

87

78

9

54

80

71

9

9

Overall mortality

87

78

9

1

80

71

9

2

Cardiovascular mortality

87

78

9

1

80

71

9

2

Non‐cardiovascular mortality

87

78

9

0

80

71

9

0

Revascularisation procedures

87

78

9

1

80

71

9

4

Fatal or non‐fatal stroke

87

78

9

0

80

71

9

1

Discontinuation of treatment due to side effects

87

80

7

2

80

77

3

6

ALPINE‐SVG 2015

Fatal or non‐fatal myocardial infarction

19

19

0

0

19

19

0

1

Fatal and non‐fatal stroke

19

19

0

0

19

19

0

1

Revascularisation procedures

19

19

0

3

19

19

0

1

Capuzzi 2003

Flushing

72

60

12

21

46

43

3

0

Pruritus

72

60

12

5

46

43

3

0

Rash

72

60

12

6

46

43

3

0

Discontinuation of treatment due to side effects

72

67

5

7

46

44

2

1

Carotid IMT 2008

Fatal or non‐fatal myocardial infarction

214

180

34

0

218

204

14

1

Discontinuation of treatment due to side effects

214

203

11

23

218

211

7

7

CDP 1975

Overall mortality

1119

1116

3

273

2798

2797

1

709

Cardiovascular mortality

1119

1116

3

238

2798

2797

1

633

Non‐cardiovascular mortality

1119

1116

3

30

2798

2797

1

54

Fatal myocardial infarction

1119

1116

3

203

2798

2797

1

535

Non‐fatal myocardial infarction

1119

1116

3

114

2798

2797

1

386

Fatal or non‐fatal myocardial infarction

1119

1116

3

287

2798

2797

1

839

Fatal or non‐fatal stroke

1119

1116

3

95

2798

2797

1

311

Revascularisation procedures

1119

1116

3

29

2798

2695

103

132

Gastrointestinal symptoms

1119

1073

46

230

2798

2695

103

385

Flushing

1119

1073

46

987

2798

2695

103

115

Pruritus

1119

1073

46

525

2798

2695

103

167

Rash

1119

1073

46

289

2798

2695

103

199

Goldberg 2000

Flushing

87

87

0

74

44

44

0

7

Headache

87

46

41

22

44

34

10

13

Gastrointestinal symptoms

87

46

41

24

44

34

10

10

Pruritus

87

46

41

10

44

34

10

0

Rash

87

46

41

9

44

34

10

0

Overall mortality

87

46

41

0

44

34

10

1

Discontinuation of treatment due to side effects

87

72

15

26

44

39

5

5

Guyton 2008

Overall mortality

676

391

285

0

272

213

59

0

Fatal or non‐fatal myocardial infarction

676

391

285

1

272

213

59

1

Fatal or non‐fatal stroke

676

391

285

0

272

213

59

1

Flushing

676

457

219

66

272

214

58

1

New onset diabetes

569

NR

NR

25

229

NR

NR

2

Discontinuation of treatment due to side effects

676

547

129

156

272

NR

33

26

Harikrishnan 2008

Flushing

104

102

2

2

106

NR

4

0

Gastrointestinal symptoms

104

102

2

5

106

102

4

2

Discontinuation of treatment due to side effects

104

102

2

4

106

102

4

1

Heart positive 2011

Gastrointestinal symptoms

92

49

43

1

88

53

35

2

Rash

723

412

311

1

315

237

78

2

Headache

780

493

287

2

378

315

63

0

Flushing

92

49

43

28

88

53

35

5

HPS2‐THRIVE 2014

Fatal or non‐fatal myocardial infarction

12838

12730

108

668

12835

12745

90

694

Non‐fatal myocardial infarction

12838

12730

108

402

12835

12745

90

431

Non‐cardiovascular mortality

12838

12730

108

350

12835

12745

90

321

Fatal myocardial infarction

12838

12730

108

302

12835

12745

90

291

Cardiovascular mortality

12838

12730

108

448

12835

12745

90

411

Fatal or non‐fatal stroke

12838

12730

108

498

12835

12745

90

499

Revascularisation procedures

12838

12730

108

807

12835

12745

90

897

Overall mortality

12838

12730

108

798

12835

12745

90

732

New onset diabetes

8704

NR

NR

494

8670

NR

NR

376

Gastrointestinal symptoms

12838

12730

108

620

12835

12745

90

491

Rash

12838

12730

108

54

12835

12745

90

33

Discontinuation of treatment due to side effects

12838

12730

108

2105

12835

12740

95

1014

Hunninghake 2003

Flushing

57

57

0

6

61

61

0

1

Overall mortality

57

57

0

0

61

61

0

1

Headache

57

57

0

5

61

61

0

2

Pruritus

57

57

0

4

61

61

0

1

rash

57

57

0

1

61

61

0

2

Discontinuation of treatment due to side effects

57

57

0

11

61

61

0

6

Lee 2009

Gastrointestinal symptoms

35

25

10

3

36

30

6

1

Discontinuation of treatment due to side effects

35

29

6

7

36

31

5

2

Lee 2011

Discontinuation of treatment due to side effects

14

14

0

0

14

14

0

0

Linke 2009

flushing

30

30

0

19

30

30

0

0

Overall mortality

30

30

0

0

30

30

0

0

Maccubbin 2008

Rash

1343

917

426

33

270

239

31

2

Discontinuation of treatment due to side effects

1339

1080

259

166

270

254

16

15

Overall mortality

1343

917

426

3

270

239

31

0

Pruritus

1343

917

426

34

270

239

31

6

Flushing

1343

917

426

142

270

239

31

5

Gastrointestinal symptoms

1343

917

426

34

270

239

31

5

New onset diabetes

1129

NR

NR

7

232

NR

NR

2

MacLean 2011

Discontinuation of treatment due to side effects

454

400

54

102

342

308

34

31

Overall mortality

454

298

156

0

342

277

65

1

Fatal or non‐fatal myocardial infarction

454

298

156

2

342

277

65

0

Gastrointestinal symptoms

454

298

156

68

342

277

65

38

Pruritus

454

298

156

71

342

277

65

9

Rash

454

298

156

26

342

277

65

5

Flushing

454

298

156

79

342

277

65

16

Nash 2011

Gastrointestinal symptoms

31

31

0

2

23

23

0

0

Discontinuation of treatment due to side effects

31

31

0

4

23

23

0

1

NIA Plaque 2013

Revascularisation procedures

72

59

13

5

73

58

15

2

Fatal or non‐fatal stroke

72

59

13

1

73

58

15

0

Overall mortality

72

59

13

0

73

58

15

1

Flushing

72

59

13

7

73

58

15

1

Discontinuation of treatment due to side effects

72

66

6

11

73

63

10

5

PAST 1995

Overall mortality

40

30

10

3

45

34

11

4

Fatal myocardial infarction

40

30

10

2

45

34

11

3

Cardiovascular mortality

40

30

10

2

45

34

11

3

Non‐cardiovascular mortality

40

30

10

1

45

34

11

1

Fatal or non‐fatal myocardial infarction

40

30

10

2

45

34

11

1

Revascularisation procedures

40

30

10

2

45

34

11

4

Discontinuation of treatment due to side effects

40

34

6

4

45

34

11

0

Sang 2009

Rash

52

52

0

1

56

56

0

0

Flushing

52

52

0

4

56

56

0

0

Gastrointestinal symptoms

52

52

0

1

56

56

0

0

Revascularisation procedures

52

52

0

2

56

56

0

1

Overall mortality

52

52

0

0

56

56

0

1

Fatal myocardial infarction

52

52

0

0

56

56

0

1

Schoch 1968

Gastrointestinal symptoms

141

134

7

71

284

277

7

57

Flushing

141

134

7

71

284

277

7

20

Overall mortality

141

140

1

31

284

283

1

54

Fatal myocardial infarction

141

134

7

28

284

277

7

48

Non‐fatal myocardial infarction

141

134

7

21

284

277

7

45

Fatal or non‐fatal myocardial infarction

141

134

7

49

284

277

7

93
Figures and Tables -
Table 3. Number randomised, complete, missing, and events
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Comparison 1. Niacin versus control, maximum follow‐up, available case analysis

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Overall mortality Show forest plot

12

35543

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.97, 1.12]

2 Overall mortality, sensitivity analysis with stratification by risk of bias trials only Show forest plot

12

35543

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.97, 1.12]

2.1 High risk of bias

10

6703

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.87, 1.09]

2.2 Low risk of bias

2

28840

Risk Ratio (M‐H, Random, 95% CI)

1.10 [1.00, 1.20]

3 Fatal myocardial infarction Show forest plot

6

33336

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.91, 1.11]

4 Cardiovascular mortality Show forest plot

5

32966

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.93, 1.12]

5 Non‐cardiovascular mortality Show forest plot

5

32966

Risk Ratio (M‐H, Random, 95% CI)

1.12 [0.98, 1.28]

6 Non‐fatal myocardial infarction Show forest plot

4

33164

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.77, 1.07]

7 Fatal or non‐fatal myocardial infarction Show forest plot

9

34829

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.87, 1.00]

8 Fatal and non‐fatal stroke Show forest plot

7

33661

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.74, 1.22]

9 Revascularisation procedures Show forest plot

8

33130

Risk Ratio (M‐H, Random, 95% CI)

0.85 [0.68, 1.06]

10 Flushing Show forest plot

15

11038

Risk Ratio (M‐H, Random, 95% CI)

7.69 [4.14, 14.28]

11 Pruritus Show forest plot

6

5800

Risk Ratio (M‐H, Random, 95% CI)

5.26 [2.68, 10.32]

12 Rash Show forest plot

9

31485

Risk Ratio (M‐H, Random, 95% CI)

3.15 [1.94, 5.13]

13 Headache Show forest plot

3

300

Risk Ratio (M‐H, Random, 95% CI)

1.40 [0.86, 2.28]

14 Gastrointestinal symptoms Show forest plot

12

35353

Risk Ratio (M‐H, Random, 95% CI)

1.69 [1.37, 2.07]

15 Discontinuation of treatment due to side effects Show forest plot

17

33539

Risk Ratio (M‐H, Random, 95% CI)

2.17 [1.70, 2.77]

16 New onset diabetes) Show forest plot

3

27982

Risk Ratio (M‐H, Random, 95% CI)

1.32 [1.16, 1.51]
Figures and Tables -
Comparison 1. Niacin versus control, maximum follow‐up, available case analysis
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