Intervention Review

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Rivastigmine for vascular cognitive impairment

  1. Jacqueline Birks1,*,
  2. Bernadette McGuinness2,
  3. David Craig3

Editorial Group: Cochrane Dementia and Cognitive Improvement Group

Published Online: 31 MAY 2013

Assessed as up-to-date: 12 FEB 2013

DOI: 10.1002/14651858.CD004744.pub3


How to Cite

Birks J, McGuinness B, Craig D. Rivastigmine for vascular cognitive impairment. Cochrane Database of Systematic Reviews 2013, Issue 5. Art. No.: CD004744. DOI: 10.1002/14651858.CD004744.pub3.

Author Information

  1. 1

    University of Oxford, Centre for Statistics in Medicine, Oxford, UK

  2. 2

    National University of Ireland, School of Medicine, Galway, Ireland

  3. 3

    Queen's University Belfast, Department of Geriatric Medicine, Belfast, Northern Ireland, UK

*Jacqueline Birks, Centre for Statistics in Medicine, University of Oxford, Wolfson College, Linton Road, Oxford, OX2 6UD, UK. jacqueline.birks@csm.ox.ac.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 31 MAY 2013

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Characteristics of included studies [ordered by study ID]
Ballard 2008

MethodsRandomized, multicentre, double-blind, placebo-controlled trial of 24-week duration


Participants710 participants; diagnosis of probable vascular dementia (DSM-IV, NINDS-AIREN) plus MRI evidence, age 50-85 (mean = 72.8 ± 8.0), MMSE 10-24 (mean 19.2 ± 4.0), 38% female


InterventionsRivastigmine:12 mg/day (mean dose 9.4 mg daily) and matching placebo (1:1)


OutcomesCognitive, global, clinician's impression, functional and neuropsychiatric measures VaDAS, ADCS-CGIC, NPI, ADCS-ADL MMSE, Global Deterioration Scale (GDS)


NotesExploratory subgroup analyses were specified to investigate hypothesis that better response expected from those more likely to have concomitant AD (age < 75 vs age ≥ 75, MTA vs no MTA)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskCentral randomization system

Allocation concealment (selection bias)Low riskCentral allocation system

Blinding (performance bias and detection bias)
All outcomes
Low riskAttempt made to blind until study completion. Matching placebo. ADCS-CGIC assessed by independent clinician, not otherwise involved in care of the trial participants

Incomplete outcome data (attrition bias)
All outcomes
Low risk8 participants lost to follow up; 12 deaths

Selective reporting (reporting bias)Low riskAll predetermined outcomes described

Mok 2007

MethodsRandomized, double-blind, placebo-controlled trial of 26-week duration


Participants40 participants; subcortical vascular dementia diagnosis included CT or MRI evidence, aged 40-90, mean 74.9 ± 6.0, MMSE 3-24 mean 13.2 ± 5.1


InterventionsRivastigmine (mean dose 6 mg daily) and matching placebo


OutcomesCognitive, neuropsychiatric, global and functional measures. Chinese version of MMSE, FAB, Chinese version of NPI and IADL, CDR


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomization stated as being done via computerisation process

Allocation concealment (selection bias)High riskNot reported

Blinding (performance bias and detection bias)
All outcomes
High riskNot reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk1 death; 30% withdrawal rate in active arm

Selective reporting (reporting bias)Low riskAll predetermined outcomes described

Narasimhalu 2010

MethodsRandomized, double-blind, placebo-controlled trial of 24-week duration


Participants40 participants; aged 55-85 mean = 68.7 ± 8.5, 66% female, 70% Chinese, diagnosis of post-stroke cognitive impairment (DSM-IV and MRI evidence), MMSE 16-29, mean 23.8 ± 3.4


InterventionsRivastigmine (up to 9 mg daily) and matching placebo


OutcomesCognitive, functional, global and neuropsychiatric measures. MMSE, Clock test, Color trails, ADAS-Cog, cognitive battery, FAB, ADCS-ADL MCI, NPI, Geriatric Depression Scale (GDS)


NotesDose titration from 1.5 mg twice a day up to a maximum of 4.5 mg twice a day with complete flexibility


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskCentral randomization scheme

Allocation concealment (selection bias)Low riskBlinded allocation personnel

Blinding (performance bias and detection bias)
All outcomes
Low riskAttempt made to blind all assessors until study completion

Incomplete outcome data (attrition bias)
All outcomes
Low risk8% death rate overall; 12% and 20% withdrawal rates in active and placebo arms due to adverse events

Selective reporting (reporting bias)Low riskAll predetermined outcomes described

 
Comparison 1. Rivastigmine (3-12 mg/day) vs placebo for probable vascular dementia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 VaDAS (change from baseline at 24 weeks) ITT1Mean Difference (IV, Random, 95% CI)Totals not selected

 2 MMSE (change from baseline at 24 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 3 ADAS-Cog (change from baseline at 24 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 4 ADCS-CGIC 24 weeks ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 5 GDS global deterioration scale (change from baseline at 24 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 6 Behavioural disturbance NPI-12 (change from baseline at 24 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 7 ADCS-ADL (change from baseline at 24 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 8 Withdrawals before end of treatment at 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 9 Withdrawals due to adverse event by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 10 Deaths by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 11 At least one adverse event of nausea by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 12 At least one adverse event of vomiting by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 13 At least one adverse event of diarrhoea by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 14 At least one adverse event of dizziness by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 15 At least one adverse event of a fall by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 16 At least one adverse event of hypertension by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 17 At least one adverse event of hypotension by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 18 At least one adverse event of headache by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 19 At least one adverse event of anorexia by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 20 At least one adverse event of bradycardia by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 21 At least one serious adverse event by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 22 At least one serious adverse event due to, or potentially due to a cerebrovascular accident by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 2. Rivastigmine (6 mg/day) vs placebo for subcortical vascular dementia

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 MMSE (change from baseline at 26 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 2 FAB (change from baseline at 26 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 3 Global function CDR sum of boxes (change from baseline at 26 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 4 Behavioural disturbance NPI-12 (change from baseline at 26 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 5 IADL (change from baseline at 26 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 6 Withdrawals before end of treatment at 26 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 7 At least one adverse event by 26 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 8 At least one adverse event of recurrent stroke by 26 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 9 Deaths by 26 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 
Comparison 3. Rivastigmine (3-9 mg/day) vs placebo for MCI and CIND

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Clock drawing (change from baseline at 24 weeks) ITT149Mean Difference (IV, Fixed, 95% CI)-0.4 [-1.58, 0.78]

 2 Color trails 1149Mean Difference (IV, Fixed, 95% CI)8.7 [-20.16, 37.56]

 3 Color trails 21Mean Difference (IV, Fixed, 95% CI)Totals not selected

 4 ADAS-Cog (change from baseline at 24 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 5 Behavioural disturbance NPI (change from baseline at 24 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 6 GDS depression scale (change from baseline at 24 weeks ) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 7 ADCS-ADL (change from baseline at 24 weeks) ITT1Mean Difference (IV, Fixed, 95% CI)Totals not selected

 8 Withdrawals before end of treatment at 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 9 At least one adverse event by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 10 At least one serious adverse event by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 11 Deaths by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 12 At least one adverse event of nausea by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 13 At least one adverse event of headache by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 14 At least one adverse event of gastrointestinal upset by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 15 At least one adverse event of breathlessness by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 16 At least one adverse event of diarrhoea by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 17 At least one adverse event of dizziness by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 18 At least one adverse event of vomiting by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 19 At least one adverse event of chest pain by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected

 20 At least one adverse event of accidental fall by 24 weeks1Odds Ratio (M-H, Fixed, 95% CI)Totals not selected