Table A16-21Acetylcholinesterase inhibitors (minimum dose) vs. placebo for the treatment of cognitive symptoms of vascular dementia

Quality assessmentSummary of findings
No of patientsEffectQualityImportance
No of studiesDesignLimitationsConsistencyDirectnessOther considerationscholinesterase inhibitors (minimum dose)placeboRelative (95% CI)Absolute (95% CI)
Overall clinical response (LOCF) (Defined as improved or no change on CIBIC-plus,9 Follow up: at end of treatment (24 wks))
1Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1152/196 (77.6%)134/194 (69.1%)RR 1.12 (1.00 to 1.27)80/1 000 (0 to 170)⊕⊕⊕○
Moderate
9
Overall clinical response (Observed case) (Defined as improved or no change on CIBIC-plus, Follow up: at end of treatment (24 weeks))
1Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1
High probability of reporting bias (− 1)3,
126/160 (78.8%)112/162 (69.1%)RR 1.14 (1.00 to 1.30)100/1 000 (0 to 190)⊕⊕○○
Low
6
Overall clinical improvement (LOCF) (Defined as improved on CIBIC-plus, Follow up: at end of treatment (24 wks))
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1149/398 (37.4%)105/382 (27.5%)RR 1.36 (1.11 to 1.68)100/1 000 (30 to 160)⊕⊕⊕○
Moderate
9
Overall clinical improvement (Observed case) (Defined as improved on CIBIC-plus, Follow up: at end of treatment (24 wks))
1Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1,
High probability of reporting bias (− 1)3,
61/160 (38.1%)52/162 (32.1%)RR 1.196, (0.88 to 1.60)60/1 000 (−40 to 160)⊕⊕○○
Low
6
Cognitive symptoms (LOCF) (ADAS-cog,10 Range: 1 to 70. Better indicated by: lower scores)
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1384368-WMD −1.667, (−2.40 to −0.92)⊕⊕⊕○
Moderate
9
Cognitive symptoms (Observed case) (ADAS-cog, Range: 0 to 70. Better indicated by: lower scores)
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1
High probability of reporting bias (− 1)3,
317310-WMD −1.66 (−2.45 to −0.87)⊕⊕○○
Low
6
Activities of Daily Living (LOCF) (ADFACS,5 Range: 0 to 24. Better indicated by: lower scores)
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1383368-WMD −0.73 (−1.52 to 0.06)⊕⊕⊕○
Moderate
9
Activities of Daily Living (Observed case) (ADFACS, Range: 0 to 24. Better indicated by: lower scores)
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1
High probability of reporting bias (− 1)3,
317312-WMD −0.976, (−1.80 to −0.14)⊕⊕○○
Low
6
Instrumental Activities of Daily Living (LOCF) (ADFACS, Range: 0 to 30. Better indicated by: lower scores)
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1383368-WMD −0.70 (−1.28 to −0.12)⊕⊕⊕○
Moderate
9
Instrumental Activities of Daily Living (Observed case) (ADFACS, Range: 0 to 30. Better indicated by: lower scores)
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)1
High probability of reporting bias (− 1)3,
317312-WMD −0.81 (−1.45 to −0.16)⊕⊕○○
Low
6
Any adverse event ( Follow up: at end of treatment (24 wks))
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)877/406 (19%)62/392 (15.8%)RR 1.20 (0.88 to 1.62)30/1 000 (−20 to 80)⊕⊕⊕○
Moderate
6
Leaving the study early for any reason ( Follow up: )
2Randomised trialsNo limitationsImportant inconsistency (−1)2No uncertaintyImprecise or sparse data (−1)8319/1277 (25%)191/1028 (18.6%)RR 1.36 (1.07 to 1.71)70/1 000 (20 to 120)⊕⊕○○
Low
9
Leaving the study early due to adverse events ( Follow up: at end of treatment (24 wks))
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)843/406 (10.6%)39/392 (9.9%)RR 1.07 (0.71 to 1.61)10/1 000 (−40 to 50)⊕⊕⊕○
Moderate
9
Mortality ( Follow up: at end of treatment (24 wks))
2Randomised trialsNo limitationsImportant inconsistency (−1)2No uncertaintyImprecise or sparse data (−1)84/406 (1%)5/392 (1.3%)RR 0.82 (0.08 to 8.69)0/1 000 (−30 to 20)⊕⊕○○
Low
9
AE: Body as a whole - Accidental injury (donepezil vs. placebo) ( Follow up: )
1Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)835/208 (16.8%)19/193 (9.8%)RR 1.71 (1.01 to 2.88)70/1 000 (0 to 140)⊕⊕⊕○
Moderate
9
AE: Cardiovascular - Bradycardia (donepezil vs. placebo) ( Follow up: at the end of treatment (24 wks))
1Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)87/198 (3.5%)3/199 (1.5%)RR 2.35 (0.62 to 8.94)20/1 000 (−10 to 50)⊕⊕⊕○
Moderate
9
AE: Digestive system - Anorexia (donepezil vs. placebo) ( Follow up: at end of treatment (24 wks))
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)828/406 (6.9%)14/392 (3.6%)RR 1.90 (1.02 to 3.54)30/1 000 (0 to 60)⊕⊕⊕○
Moderate
9
AE: Digestive system - Diarrhoea (donepezil vs. placebo) ( Follow up: at end of treatment (24 wks))
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)859/406 (14.5%)40/392 (10.2%)RR 1.43 (0.98 to 2.08)40/1 000 (0 to 90)⊕⊕⊕○
Moderate
9
AE: Nervous system - Insomnia (donepezil vs. placebo) ( Follow up: at end of treatment (24 wks))
1Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyImprecise or sparse data (−1)822/208 (10.6%)12/193 (6.2%)RR 2.04 (0.99 to 4.20)50/1 000 (0 to 110)⊕⊕⊕○
Moderate
9
AE: Other - Cramps/leg cramps (donepezil vs. placebo) ( Follow up: at end of treatment (24 wks))
2Randomised trialsNo limitationsNo important inconsistencyNo uncertaintyVery strong association (+2)1126/406 (6.4%)4/392 (1%)RR 6.36 (2.23 to 18.10)50/1 000 (30 to 80)⊕⊕⊕⊕
High
9
1

CI compatible with both benefit and no benefit

2

Random effects model used due to heterogeneity

3

Observed case analysis with higher attrition in the active treatment group

4

One relatively small study

5

ADFACS = Alzheimer's Disease Functional Assessment and Change Scale

6

Calculated using a random effects model

7

Unless otherwise indicated, negative effect sizes favour active treatment

8

CI compatible with both harm and no harm

9

CBIC = Clinician's Interview-Based Impression of Change-Plus version

10

ADAS-cog = Alzheimer's Disease Assessment Scale-cognitive subscale

11

RR > 5, p < .01

From: APPENDIX 16, EVIDENCE PROFILE TABLES FOR QUANTITATIVE REVIEWS

Cover of Dementia
Dementia: A NICE-SCIE Guideline on Supporting People With Dementia and Their Carers in Health and Social Care.
NICE Clinical Guidelines, No. 42.
National Collaborating Centre for Mental Health (UK).
Leicester (UK): British Psychological Society; 2007.
Copyright © 2007, The British Psychological Society & The Royal College of Psychiatrists.

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