Table 1 Characteristics of included studies, stratified by outcome

 Barnett, 2007, [28] USA

Cohort

Veterans with dementia aged ≥65 years, identified between 2002 and 2003 from the Veterans Administration and Medical Provider and Analysis Review database

14,029

78

97

1.5 years

New AP drug use (excluding clozapine and injectable APs)

Hospitalisation for or death from CVE

 Chan, 2010, [29] China

Cohort

Hong Kong residents with dementia aged ≥65 years, identified between 2000 and 2007 from the Pamela Youde Nethersole Eastern Hospital

1089

81

34

1019 days

New AP drug use

Hospitalization for CVE

 Chen, 2008, [30] USA

Nested Case-control

People with depression and without a history of stroke between 1998 to 2002, identified from the PHARMetrics database

7601

NR(66.4% aged 35–64)

37

Minimum of 6 months

Any use of risperidone (SGA)

First diagnosis of stroke

 Correll, 2015, [31] USA

Cohort

People aged 18–65 years without a history of hypertension, diabetes, obesity or CHD, identified between 2006 and 2010 from Thomson Reuters MarketScan Research insurance database

284,234

44.5

29

1.5 years

Any SGA use for at least 4 weeks

First diagnosis of stroke or TIA (from inpatient and outpatient records)

 Douglas, 2008, [32] UK

SCCS

People registered with a GP in England/Wales, AP prescribed 1988–2002; identified from the General Practice Research Database

6790

80

36

0.4 years

Any AP use

First stroke diagnosis (no ICD codes reported)

 Franchi, 2013, [33] Italy

Case control

Community dwelling seniors of Lombardy aged 65–94 years between 2003 and 2005; identified from the Lombardy Regional Databases

19,275

NR

46

NR

≥2 boxes of any AP dispensed

Hospitalisation for stroke

 Hsieh, 2013, [34] Taiwan

Nested Case-control

People with schizophrenia identified between 2001 and 2009 from the National Health Insurance Research Database

1158

57.3^b

50

957^b days

Any AP use

First diagnosis of stroke^c or TIA (from inpatient and outpatient records)

 Kleijer, 2009, [35] Netherlands

Nested Case-control

Community dwelling adults aged > 50 years, starting an antipsychotic between 1986 and 2003 and identified from the national prescription, vital statistics and health registries databases

2548

76

44

Minimum of 8 years

Any AP use

Hospitalisation for Stroke^c or TIA

 Lan, 2015, [36] Taiwan

Cohort

People with bipolar disorder identified between 2001 and 2006 from the National Health Insurance Research Database

3681

43

42

11 years maximum

Any AP use

First hospitalisation for (or death from) stroke^c (not including TIA)

 Laredo, 2011, [37] UK

Nested Case-control

People aged ≥65 years diagnosed with dementia and GP registered in 1995, identified from the General Practice Research Database

18,762

81^b

30^b

12 years

Any AP drug use

First stroke diagnosis^c

 Liebetrau, 2008, [38] Sweden

Cohort

85 year olds in community/institutions registered with Gothenburg census who completed survey and neuro-psychiatric exam 1986–87

401[281]

85

30

3 years (29% loss to follow up)

Any AP drug use

First diagnosis of stroke^c

 Liperoti, 2005, [39] USA

Nested Case-control

Nursing home residents aged ≥65 years between 1998 and 1999, diagnosed with dementia and identified from the Systematic Assessment of Geriatric drug use via Epidemiology database

4788

NR(50.7% aged > 85)

29^b

Maximum of 3 months

Any AP use within the 3 months prior to the index date

Hospitalisation for ischemic stroke or TIA

 Liu, 2013, [40] Taiwan

Cohort

People aged ≥65 years, diagnosed with dementia between 2003 and 2005, identified from the Longitudinal Health Insurance Database 2005

8957 [2243]

78

47

2.6 years

Any AP use

First diagnosis of CVE

 Percudani, 2005, [41] Italy

Cohort

Residents of Lombardy region between 2001 and 2002 aged ≥65 years, identified from Lombardy regional databases

1,645,978

NR

NR

1 year

Any AP use during 2001

Hospitalisation for stroke^c or TIA

 Pratt, 2010, [42] Australia

SCCS

Veterans aged ≥65 years, with stroke diagnosis between 2003 and 06, identified from the Australian Department of Veterans Administration claims database

10,638

84

NR

3–4 years

New AP drug use (excluded if using FGA and SGA together or injectable APs)

Hospitalization for stroke^c

 Sacchetti, 2008, [43] Italy

Cohort

People aged ≥65 years between 2000 and 2003, identified from the Health Search Database

74,162

76^b

42^b

maximum of 4 years

New AP drug use

First diagnosis of stroke

 Shin, 2013, [44] Korea

Case Crossover

People aged 65–100 years diagnosed with a stroke between 2005 and 2006; identified from the Korean Health Insurance Review and Assessment Service

1601

76

42

150 days

Any SGA use (respiridone, quetiapine or olanzapine) within the 30-day case and 60-day control period

First hospitalisation for ischemic stroke

 Wang, 2012, [45] USA

Case-case-time control

Veterans diagnosed with a stroke between 2002 and 2007, with one physician visit and prescription in the year before hospitalization; identified from the

Veterans Health Administration database

511

NR (69.1% were aged 60–90)

98^b

120 days

Any AP use with at least 3 days duration in 30-day case or control periods

First hospitalization for ischaemic stroke

 Wu, 2012, [46] Taiwan

Case Crossover

People aged ≥18 years with incident stroke between 1998 and 2007, identified from the

National Health Insurance Research Database

14,584

69

49

1 year

Any AP use in year prior to stroke (excluding prochlorperazine, melitracen-flupentixol and injectable APs)

First hospitalisation for stroke^c or TIA

 Brauer, 2015, [47] UK

Case-control

People aged ≥18 years and enrolled with a GP between 1987 and 2010, identified through the Clinical Practice Research Datalink database

136,095

67^b

68^b

Minimum of 1 year

Any current AP use within 90 days of outcome

MI diagnosis

 Correll, 2015, [31] USA

Cohort

People aged 18–65 years enrolled between 2006 and 2010 by Thomson Reuters MarketScan Research insurance database

284,234

45

29

1.5 years

Use of any SGA for at least 4 weeks

MI diagnosis

 Enger, 2004, [48] USA

Cohort

People aged 15–64 years enrolled in United Healthcare between 1995 and 1999, diagnosed with schizophrenia and being treated with antipsychotics, matched to general population controls identified from an affiliated research database

11,520

40

42

1.5 years

Any AP use

Hospitalization for MI

 Hwang, 2014, [49] Canada

Cohort

Community and long-term care residents in Ontario, aged > 65 years between 2003 and 2011, identified from linked Ontario public prescription, vital statistics and health registries

195,554

81

36

90 days

Any new SGA use (quetiapine, olanzapine and risperidone)

Hospitalization for MI

 Lin, 2014, [50] Taiwan

Case Crossover

People aged ≥18 years with schizophrenia, mood or dementia disorder, prescribed antipsychotics and who had a first AMI between 1999 and 2009, identified from the Taiwan’s National Insurance Research Database

56,910

72

52

120 days

Any AP use

First MI hospitalization

 Nakawaga, 2006, [51] Denmark

Case-control

Danish residents aged ≥15 years, identified 1992 to 2003 from the Danish Civil Registry and Medical Database

128,262

70

61

1 year

Any current AP use (within 90 days prior to index date)

Hospitalization for MI

 Pariente, 2012, [52] Canada

Cohort

Community-dwelling residents with dementia and aged > 65 years, in Quebec, Canada, identified 2000–2009 from public prescription and medical service database

21,938

NR(53% aged > 79)

34

Maximum of 1 year

Any new AP use

Hospitalisation for MI

 Penttinen, 1996, [53] Finland

Case-control

Finnish farmers born between 1935 and 1958; without a history of CVD and recruited between 1980 and 1992, with data collected from questionnaires and medical records

332

NR (Range: 22–57)

100

100

Any AP use

First MI hospitalization/ death from MI

 Pratt, 1996, [54] USA

Cohort

Baltimore residents aged > 18 years without a history of ‘heart trouble’, recruited via household interviews

1551

NR(67% aged < 45)

37

13 years (28% loss to follow up)

Any use of SGA

First non-fatal MI (self-report)

 Wang, 2011, [55] USA

Case-case time control

Veterans aged 50–90 years, identified between 2002 and 2007 from the Veterans Health Database

NR

NR

NR

120 days

NR

Hospitalization for MI