Table 2 Studies on the risk of cerebrovascular events associated with antipsychotic medicines
Study | Population | Outcome | Propensity for bias / Study quality | Procedures to minimize bias | Follow-up | Outcome Rate in reference group | Result |
|---|---|---|---|---|---|---|---|
LEVEL I Evidence: Meta-Analyses | |||||||
Studies that compared atypical antipsychotic (ATYP) treatment to placebo (PLA) | |||||||
Ballard [1] | 1954 dementia patients (age> 60) | CV Events | Low/High | Yes | 10-13 weeks | 1.0% | RR (RISP v PLA); 3.64 95% CI; 1.72-7.69 |
Schneider [6] | 5,110 Dementia patients (mean age 81.2) | CV Events | Low/High | Yes | 6-26 weeks | 0.9% 1.0% | OR (ATYP v PLA); 2.13 95% CI; 1.20-3.75 OR(RISP v PLA); 3.43 95%CI; 1.60-7.32 |
DeDeyn [4] | 1,155 Institutionalised patients (age>=55) | CV Events | Low/High | Yes | 12 weeks | 1.6% | Rate in Risperidone group 3.9% RR not reported |
Hermann [32] | 1,721 Dementia patients (age>=55) | CV Events | Low/High | Yes | 12 weeks | 1.1% | RR (RISP v PLA); 3.2 95% CI; 1.4-7.2 |
Katz [5] | 895 Institutionalised dementia patients (age>=55) | CV Events | Low/High | Yes | 12 weeks | 0.8% | Rate in Risperidone group 1.6% RR not reported |
DeDeyn [4] | 1,155 Institutionalised patients (age>=55) | Serious CV Event requiring hosp. | Low/High | Yes | 12 weeks | 0.7% | Rate in Risperidone group 1.6% RR not reported |
Hermann [32] | 1,721 Dementia patients (age>=55) | Serious CV Event requiring hosp. | Low/High | Yes | 12 weeks | 0.6% | RR (RISP v PLA); 2.3 95% CI; 0.5-10.7 |
LEVEL III Evidence: Observational Studies | |||||||
Studies that compared atypical antipsychotic (ATYP) treatment to non-use (NU) | |||||||
COHORT STUDIES | |||||||
Sacchett [33] | 74,162 All patients, General Practitioner Health Search database (Italy) (age>=65) | Diagnosis of stroke (GPs’ medical records) ICD9: 434.9, 438.0, 342 | Moderate/Moderate | Yes (covariate adjustment, subgroup analysis) | 3.5 months | 12 per 1000py | RR (ATYP v UNEX); 2.46 95% CI; 1.07-5.65 |
Barnett [34] | 14,029 Dementia patients, Veterans Affairs Clients (US) (age>=65) | Hospital Admission for CV event ICD9 435, 437, 430, 432, 433, 434 | Moderate/Moderate | Yes (covariate adjustment, sensitivity analysis) | 18 months | 3.2% | HR (ATYP v NU); 1.20 95% CI; 0.83-1.74 |
CASE-CONTROL STUDIES | |||||||
Kolanowski [35] | 959 Dementia patients, health care insured on Southeast US (age>70) | Diagnosis of Stroke | Moderate/ Low | Yes (unmatchedcovariate adjustment) | 45 days | NA | OR (ATYP v NU); 0.98 95% CI; 0.64-1.52 |
Liperoti [36] | 1130 cases, 3658 controls, institutionalised dementia patients in six states in the US (Ohio, Maine, Illinois, Mississippi, South Dakota, New York) (age>85) | Hospital Admission for CV event ICD9 433.0-434.9 (Ischaemic stroke) 435-435.9 (TIA) | Moderate/ Low | Yes (matching on admitted to same facility for septicemia, UTI) | NR | NA | OR (RISP v NU); 0.87 95% CI; 0.67-1.12 OR (OLA v NU); 1.32 95% CI; 0.83-2.11 OR (Other ATYP v NU); 1.57 95% CI; 0.65-3.82 |
SELF-CONTROLLED CASE-SERIES STUDIES | |||||||
Douglas [37] | 6790 All patients with incident diagnosis of stroke General Practice Research Database (UK) (no age restriction) | Diagnosis of stroke (GPs’ medical records, excluding TIA) | Moderate/Moderate | Yes (within patient design) | NR | NA | IRR (ATYP v NU); 2.32 95% CI; 1.73-3.10 |
Pratt [38] | 10638 Australian Department of Veterans Affairs Veterans/spouses with hospitalization for stroke (Australia) (age>=65) | Hospitalis-ation for stroke ICD-10: I60-I64 | Moderate/Moderate | Yes (within patient design) | 4 years | NA | IRR (ATYP v NU); 0.9 95% CI; 0.7-1.0 |
Studies that compared conventional antipsychotic (CONV) treatment to non-use (NU) | |||||||
COHORT STUDIES | |||||||
Sacchetti [33] | 74,162 All patients, General Practitioner Health Search database (Italy) (age>=65) | Diagnosis of stroke (GPs’ medical records) ICD9: 434.9, 438.0, 342 | Moderate/Moderate | Yes (covariate adjustment, subgroup analysis) | 3.5 months | 12 per 1000py | RR (BUTY v UNEX); 3.55 95% CI; 1.56-8.07 RR (PHENO v UNEX); 5.79 95% CI; 3.07-10.9 |
Barnett [34] | 14,029 Dementia patients, Veterans Affairs Clients (US) (age>=65) | Hospital Admission for CV event ICD9 435, 437, 430, 432, 433, 434 | Moderate/Moderate | Yes (covariate adjustment, sensitivity analysis) | 18 months | 3.2% | HR (CONV v NU); 1.20 95% CI; 0.48-3.47 |
CASE-CONTROL STUDIES | |||||||
Kolanowski [35] | 959 Dementia patients, health care insured on Southeast US (age>70) | Diagnosis of Stroke | Moderate/ Low | Yes (Unmatched, covariate adjustment) | 45 days | NA | OR (CONV v NU); 1.18 95% CI; 0.63-2.24 |
Liperoti [36] | 1130 cases, 3658 controls, institutionalised dementia patients in six states in the US (Ohio, Maine, Illinois, Mississippi, South Dakota, New York) (age>85) | Hospital Admission for CV event ICD9 433.0-434.9 (Ischaemic stroke) 435-435.9 (TIA) | Moderate /Low | Yes (matched; on admitted to same facility for septicemia, UTI) | NR | NA | OR (CONV v NU); 1.24 95% CI; 0.95-1.63 |
SELF-CONTROLLED CASE-SERIES STUDIES | |||||||
Douglas [37] | 6790 All patients with incident diagnosis of stroke General Practice Research Database (UK) (no age restriction) | Diagnosis of stroke (GPs’ medical records, excluding TIA) | Moderate/Moderate | Yes (within patient design) | NR | NA | IRR (CONV v NU); 1.60 95% CI; 1.55-1.84 |
Pratt [38] | 10638 Australian Department of Veterans Affairs Veterans/spouses with hospitalization for stroke (Australia) (age>=65) | Hospitalis-ation for stroke ICD-10: I60-I64 | Moderate/Moderate | Yes (within patient design) | 4 years | NA | IRR (CONV v NU); 1.0 95% CI; 0.8-1.2 |
Studies that compared all antipsychotics (ANTIP) with no treatment (NU) | |||||||
COHORT STUDIES | |||||||
Percudani [39] | 1645978 All patients in Lombardy Italy with CV related Outcome in 2002 (age>=65) | Hospital Admission for CV related outcome ICD9 430--438 | Moderate/Low | Yes (unmatched covariate adjustment) | 2 years | 2.15 % | OR (ANTIP v NU); 1.24 95% CI; 1.16-1.32 |
Sacchetti [40] | 134488 All patients, General Practitioner Health Search database (Italy) (age>50) | Diagnosis of stroke (GPs’ medical records) ICD9: 434.9, 438.0, 342 | Moderate/Moderate | Yes (covariate adjustment) | 6 months | 3.6 per 1000py | 1 month: RR (ANTIP v NU); 12.4 95% CI; 8.4-18.1 |
Kleijer [41] | 2448 Patients in community pharmacy practice, PHARMO Database (Netherlands) (age>50) | Hospital Admission for stroke (inc TIA) ICD9 430-436 | Moderate/Low | Yes (matched: age/sex) | 1 year | NA | Current use: OR (ANTIP v NU); 1.6 95% CI 1.3-2.0 0-7 days: OR (ANTIP v NU); 9.9 (5.7-17.2) 8-14 days :OR (ANTIP v NU);2.6 (1.3-5.3) 15-30 days: OR (ANTIP v NU); 2.1 (1.0-4.5) 31-90 days: OR (ANTIP v NU); 1.5 (1.0-2.2) >90 days: OR (ANTIP v NU); 1.0 (0.7-1.3) |
Studies that compared conventional antipsychotic (C) and atypical antipsychotic (A) treatment | |||||||
COHORT STUDIES | |||||||
Hermann [42] | 11400 All patients, population based cohort (Canada) (age>65) | Hospital Admission for stroke ICD9 430-436 | Moderate/Moderate | Yes (covariate adjustment) | 5 years | 5.7 per 1000py | RR (RISP v CONV); 1.4 95% CI; 0.7-2.8 RR (OLA v CONV); 1.1 95% CI; 0.5-2.3 |
Gill [43] | 32710 Dementia patients, administrative health care database (Canada) (age>=65) | Hospital Admission for ischaemic stroke ICD9 431, 434,436 | Moderate/Moderate | Yes (covariate adjustment, subgroup analysis) | 5 years | 6.3 % | HR(ATYP v CONV); 1.01 95% CI; 0.81-1.26 |
Finkel [44] | 18477 Dementia patients, Medicaid database (US) (age>60) | Hospital Admission for stroke ICD( 430-432, 434-436, 437.1, 437.9 | Moderate/Moderate | Yes (covariate adjustment) | 3 months | 0.87 % | OR (OLA v RISP); 1.1 95% CI; 0.6-1.7 OR (QUE v RISP); 0.78 95% CI; 0.2-1.9 OR (HAL v RISP); 1.9 95% CI; 1.0-3.6 |
Percudani [39] | 1645978 All patients with CV related outcome in 2002 (Italy) (age>=65) | Hospital Admission for CV related outcome ICD9 430--438 | Moderate/Low | Yes (unmatched covariate adjustment) | 2 years | 2.37 % | OR (ATYP v CONV); 1.42 95% CI; 1.24-1.64 |
Wang [45] | 22890 Patients in Pharmacy Assistance Contract for Elderly Program (US) (age>=65) | Hospital Admission for stroke, cerebral hemorrhagic and ischemic events | Moderate/Moderate | Yes (Propensity score adjustment, instrumental variable analysis) | 180 days | Not Reported | 30 days: HR (CONV v ATYP); 1.08 95% CI; 0.99-1.18 60 days: HR (CONV v ATYP) 1.10 95% CI; 1.02-1.19 180 days: HR (CONV v ATYP) 1.09 95% CI; 1.02-1.16 IV analyses not reported |
Sacchetti [33] | 74,162 All patients, General Practitioner Health Search database (Italy) (age>=65) | Diagnosis of stroke (GPs’ medical records) ICD9: 434.9, 438.0, 342 | Moderate/Moderate | Yes (covariate adjustment, subgroup analysis) | 3.5 months | 47.4 per 1000py | RR (BUTY v ATYP); 1.44 95% CI; 0.55-3.76 RR (PHENO v ATYP); 2.34 95% CI; 1.01-5.41 |