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Table 1 Characteristics of included studies, stratified by outcome

From: Antipsychotic drug use and risk of stroke and myocardial infarction: a systematic review and meta-analysis

Author, year, country Study design Population Sample sizea Mean age (years) Male (%) Length of follow up Antipsychotic drug use definition Case or outcome Definition
STROKE
 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 57.3b 50 957b days Any AP use First diagnosis of strokec 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 Strokec 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) strokec (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 81b 30b 12 years Any AP drug use First stroke diagnosisc
 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 strokec
 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) 29b 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 strokec 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 strokec
 Sacchetti, 2008, [43] Italy Cohort People aged ≥65 years between 2000 and 2003, identified from the Health Search Database 74,162 76b 42b 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) 98b 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 strokec or TIA
MYOCARDIAL INFARCTION
 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 67b 68b 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
  1. aSize of subsample actually included in analyses, where relevant
  2. bWeighted average calculated by review authors based on information provided in the article
  3. cBased on broad stroke definition which includes all cranial haemorrhages and non-acute and non-acute cerebrovascular disease
  4. AMI acute myocardial infarction, AP antipsychotic, CHD coronary heart disease, CVE cerebrovascular event, FGA first generation antipsychotic, GP general practitioner, MI myocardial infarction, NR not reported, SGA second generation antipsychotic, TIA transient ischaemic attack