Helseøkonomisk evaluering
Vedlegg 4 Meta-analyser
Intravenøs trombolytisk behandling ved akutt hjerneslag vs. placebo
a) Randomised within 3 hours
Study or Subgroup
Thrombolysis Control Risk Ratio Risk Ratio
M-H, Random, 95% CI
0.01 0.1 1 10 100
Favours experimental Favours control
91
B) Randomised between 3 and 5 hours
Study or Subgroup
Test for overall effect: Z = 3.59 (P = 0.0003) Events
Thrombolysis Control Risk Ratio Risk Ratio
M-H, Random, 95% CI
0.01 0.1 1 10 100
Favours experimental Favours control
Acetylsalisylsyre +dipyridamol vs. acetylsalisylsyre
Review: Stroke rehab
Comparison: 06 Dipyridamol+aspirin vs aspirin Outcome: 01 Death
Study Treatment Control RR (random) Weight RR (random)
or sub-category n/N n/N 95% CI % 95% CI Year
Total events: 216 (Treatment), 229 (Control)
Test for heterogeneity: Chi² = 3.49, df = 5 (P = 0.62), I² = 0%
Test for overall effect: Z = 0.62 (P = 0.53)
0.1 0.2 0.5 1 2 5 10 Favours treatment Favours control
Review: Stroke rehab
Comparison:06 Dipyridamol+aspirin vs aspirin Outcome: 04 Bleeding
Study Treatment Control RR (random) Weight RR (random)
or sub-category n/N n/N 95% CI % 95% CI Year
Total events: 55 (Treatment), 52 (Control)
Test for heterogeneity: Chi² = 3.91, df = 3 (P = 0.27), I² = 23.3%
Test for overall effect: Z = 0.28 (P = 0.78)
0.1 0.2 0.5 1 2 5 10 Favours treatment Favours control
Vedlegg 5 Gradering av
dokumentasjonsgrunnlag
Intravenøs trombolytisk behandling vs. placebo
a) Randomised within 3 hours Author(s): TVR,VHA
Date: 2009-12-14
Question: Should intravenous thrombolysis within 3 hours of stroke vs placebo or open control be used in patients with stroke?
Settings:
Bibliography: Meta-anlysis on death, dependency and bleeding based on results presented in Wardlaw et al., 2009
Summary of findings Quality assessment
No of patients Effect
No of
studies Design Limitations Inconsistency Indirectness Imprecision Other considerations
Intravenous thrombolysis within 3 hours of stroke
placebo or open control
Relative
(95% CI) Absolute Quality Importance Death (follow-up mean 90 days)
83/478 Dependency (follow-up mean 90 days)
201/478 (42.1%)
105 fewer per 1000 (from 46 fewer to 151 Bleeding (follow-up mean 90 days)
8/478 (1.7%)
1 Two studies did not use ITT analysis. One study was stopped early due to safety concern. At least one study was sponsored by pharmaceutical company.
2 Total number of events is less than 300 (a threshold rule-of-thumb value) (based on:
Mueller et al. Ann Intern Med. 2007;146:878-881
<http://www.annals.org/cgi/content/abstract/146/12/878>)
3 95% confidence interval (or alternative estimate of precision) around the pooled or best estimate of effect includes both 1) no effect and 2) appreciable benefit or appreciable harm.
GRADE suggests that the threshold for "appreciable benefit" or "appreciable harm" that should be considered for downgrading is a relative risk reduction (RRR) or relative risk increase (RRI) greater than 25%.
93
B) Randomised between 3 and 5 hours Author(s): TVR,VHA
Date: 2009-12-14
Question: Should intravenous thrombolysis between 3 and 5 hours after stroke vs placebo or open control be used in patients with stroke?
Settings:
Bibliography: Meta-anlysis on death, dependency and bleeding based on results presented in Wardlaw et al., 2009
Summary of findings Quality assessment
No of patients Effect
No of
studies Design Limitations Inconsistency Indirectness Imprecision Other considerations
intravenous thrombolysis between 3 and 5 hours after
stroke
placebo or open control
Relative
(95% CI) Absolute Quality Importance Death (follow-up mean 90 days)
57/724
Dependency (follow-up mean 90 days)
230/689
Bleeding (follow-up mean 90 days)
5/724 (0.7%)
1 One study was stopped early due to safety concern.
2 Total number of events is less than 300 (a threshold rule-of-thumb value)(based on:
Mueller et al. Ann Intern Med. 2007;146:878-881
<http://www.annals.org/cgi/content/abstract/146/12/878>)
3 95% confidence interval (or alternative estimate of precision) around the pooled or best estimate of effect includes both 1) no effect and 2) appreciable benefit or appreciable harm.
GRADE suggests that the threshold for "appreciable benefit" or "appreciable harm" that should be considered for downgrading is a relative risk reduction (RRR) or relative risk increase (RRI) greater than 25%.
Acetylsalisylsyre+dipyridamol vs. acetylsalisylsyre Author(s): TVR, VHA
Date: 2009-11-06
Question: Should ASA + dipyridamol vs. ASA be used in patients with previous stroke or TIA?
Settings:
Bibliography: Meta-anlysis on vasular death and bleeding based on results presented in De Schryver et al., 2007 and Halkes et al. 2008 (recurrent stroke, myocardial infarction)
Summary of findings Quality assessment
No of patients Effect
No of
studies Design Limitations Inconsistency Indirectness Imprecision Other
considerations Dipyramidol+ASA ASA Relative
(95% CI) Absolute Quality Importance Vascular death (follow-up 22-72 months)
7 randomised
216/3842 (5.6%) 229/3844 (6%) Bleeding (follow-up 6-42 months)
5 randomised Recurrent stroke (follow-up 24-72 months)
5 randomised
341/3800 (9%) 429/3812 (11.3%)
RR 0.78 (0.68 to 0.9)
25 fewer per 1000 (from 11 fewer to 36 fewer)
MODERATE CRITICAL Myocardial infarction (follow-up 24-72 months)
5 randomised 1 The major studies contributing approx 90 % of the effect estimate was those of lowest risk
of bias. Hence, chose not to downgrade.
2 The two major studies contributing approx 95 % of the effect estimate was those of lowest risk of bias. Hence, chose not to downgrade.
3 Total number of events is less than 300 (a threshold rule-of-thumb value)(based on:
Mueller et al. Ann Intern Med. 2007;146:878-881
<http://www.annals.org/cgi/content/abstract/146/12/878>)
4 95% confidence interval (or alternative estimate of precision) around the pooled or best estimate of effect includes both 1) no effect and 2) appreciable benefit or appreciable harm.
GRADE suggests that the threshold for "appreciable benefit" or "appreciable harm" that should be considered for downgrading is a relative risk reduction (RRR) or relative risk increase (RRI) greater than 25%.
5 HR was based on 5 studies. However individual results were not presented in Halkes et al.
2008. Therefore not possible to rate inconsistency.
95
Acetylsalisylsyre+dipyridamol vs. klopidogrel Author(s): TVR,VHA
Date: 2009-12-15
Question: Should ASA + dipyridamol vs. clopidogrel be used in patients with previous stroke or TIA?
Settings:
Bibliography: Sacco et al., 2008
Summary of findings Quality assessment
No of patients Effect No of
studies Design Limitations Inconsistency Indirectness Imprecision Other
considerationsdipyramidol+ASA clopidogrel Relative
(95%
CI)
Absolute Quality Importance
Stroke (follow-up 1.5-4.4 years) 1 randomised
916/10181 (9%) 898/10151 (8.8%)
Myocardial infarct (follow-up 1.5-4.4 years) 1 randomised
Death from vascular causes (follow-up 1.5-4.4 years) 1 randomised
Hemorrhagic event (bleeding) (follow-up 1.5-4.4 years) 1 randomised
1 Based on only one study. Therefore not possible to know if results are reproducible.
Warfarin vs. acetylsalisylsyre Author(s): TVR,VHA
Date: 2009-12-15
Question: Should warfarin vs. ASA be used in patients with previous stroke or TIA and atrial fibrillation?
Settings:
Bibliography: Meta-anlysis on recurrence stroke (prior stroke, prior TIA) and bleeding Summary of findings Quality assessment
No of patients Effect
No of
studies Design Limitations Inconsistency Indirectness Imprecision Other
considerations Warfarin ASA Relative
(95% CI) Absolute Quality Importance
Recurrent Stroke (in patients with prior TIA) (follow-up 12-55 months)
0/0
Recurrent stroke (in patients with prior stroke) (follow-up 12-55 months)
0/0
Bleeding ( in patients with prior stroke or TIA and atrial fibrillation (follow-up 12-55 months)
0/0
1 Based on only one study. Therefore not possible to know if results are reproducible.