flowchart TD
A["New Dementia CPRD Download"] -- All Observations: dementia codelist --> B["n = 3,499,192 records"]
B -- Exlcluding: Schizophrenia and bipolar disorder --> BB["n = 3,359,895 records"]
BB -- date of birth < obsdate < lcd/ deregistration /date of death --> C["n = 3,336,261 records"]
C -- Earliest diagnosis after 1980-01-01 and have a dementia code after registration --> DA["n = 2,865,537 records"]
C -- Earliest diagnosis after 1980-01-01 and have a dementia code after 2000 --> DC["n = 3,254,768 records"]
C -- Earliest diagnosis after 1980-01-01 and have a dementia code after 2004 --> DB["n = 3,115,141 records"]
DA -- Unique patid: Earliest observation --> E["n = 651,863 patients"]
DC -- Unique patid: Earliest observation --> F["n = 635,404 patients"]
DB -- Unique patid: Earliest observation --> G["n = 598,807 patients"]
E -- regend > 2004-01-01 & alive or died > 2004-01-01 --> EE["n = 609,033 patients"]
F -- regend > 2004-01-01 & alive or died > 2004-01-01 --> FF["n = 613,959 patients"]
G -- regend > 2004-01-01 & alive or died > 2004-01-01 --> GG["n = 598,808 patients"]
EE -- Age: 65 or above --> EJ["n = 587,450 patients"]
FF -- Age: 65 or above --> FJ["n = 592,401 patients"]
GG -- Age: 65 or above --> GJ["n = 577,941 patients"]
EJ -- Died --> J("Yes = 290,619
No = 296,831")
EJ -- Gender --> K("Male = 213,215
Female = 374235")
EJ -- On Risperidone after 2004-01-01 --> JJ["n = 51,648 patients"]
JJ -- After diagnosis --> ZA["n = 29,810 patients"]
JJ -- < year prior to diagnosis --> ZB("n = 8,218 patients")
JJ -- > year prior to diagnosis --> ZC("n = 13,620 patients")
ZA -- Died --> XA("Yes = 15,960
No = 13,850 ")
ZA -- Gender --> XB("Male = 11,403
Female = 15,960 ")
FJ -- Died --> R("Yes = 294,389
No = 298,012")
FJ -- Gender --> Q("Male = 215,375
Female = 377,026")
FJ -- On Risperidone after 2004-01-01 --> KK["n = 52,286 patients"]
KK -- After diagnosis --> VA["n = 42,433 patients"]
KK -- < year prior to diagnosis --> VB("n = 4,439 patients")
KK -- > year prior to diagnosis --> VC("n = 5,414 patients")
VA -- Died --> YA("Yes = 23,738
No = 18,695")
VA -- Gender --> YB("Male = 16,610
Female = 25,823")
GJ -- Died --> S("Yes = 285,321
No = 292,620")
GJ -- Gender --> T("Male = 211,048
Female = 366,893")
GJ -- On Risperidone after 2004-01-01 --> LL["n = 51,887 patients"]
LL -- After diagnosis --> AA["n = 42,144 patients"]
LL -- < year prior to diagnosis --> AB("n = 6,988 patients")
LL -- > year prior to diagnosis --> AC("n = 2,755 patients")
AA -- Died --> HA("Yes = 23,568
No = 18,576")
AA -- Gender --> HB("Male = 16,516
Female = 25,628")
Flow chart of the final cohorts
Dementia incident cohort
Overall
n 445332
diagnosedbeforeRegistration = 1 (%) 351487 (78.9)
gender = 2 (%) 282903 (63.5)
died = 1 (%) 223185 (50.1)
death_composite = 1 (%) 325118 (73.0)
ONS_died = 1 (%) 291514 (65.5)
age_diagnosis (mean (SD)) 82.35 (7.02)
age_category (%)
65 - 74 64311 (14.4)
75 - 84 202073 (45.4)
85 - 94 164303 (36.9)
95+ 14645 ( 3.3)
year_of_diagnosis (%)
2004 20451 ( 4.6)
2005 17420 ( 3.9)
2006 19704 ( 4.4)
2007 17414 ( 3.9)
2008 17994 ( 4.0)
2009 19944 ( 4.5)
2010 21457 ( 4.8)
2011 22687 ( 5.1)
2012 25236 ( 5.7)
2013 27306 ( 6.1)
2014 29971 ( 6.7)
2015 29769 ( 6.7)
2016 26703 ( 6.0)
2017 26488 ( 5.9)
2018 25311 ( 5.7)
2019 24734 ( 5.6)
2020 19551 ( 4.4)
2021 20462 ( 4.6)
2022 19017 ( 4.3)
2023 13713 ( 3.1)
gender_decode = M (%) 162429 (36.5)
GP_stroke = 1 (%) 70378 (15.8)
HES_stroke = 1 (%) 56416 (12.7)
HES_stroke = 1 (%) 56416 (12.7)
stroke_composite = 1 (%) 86268 (19.4)
primary_death_stroke = 1 (%) 14705 ( 3.3)
HES_stroke = 1 (%) 56416 (12.7)
HES_stroke = 1 (%) 56416 (12.7)
ethnicity (%)
Black 8388 ( 1.9)
Mixed 1491 ( 0.3)
Other 2606 ( 0.6)
South Asian 8668 ( 1.9)
Unknown 9353 ( 2.1)
White 414826 (93.1)
pre_diagnoses_af = 1 (%) 62304 (14.0)
post_diagnoses_af = 1 (%) 28577 ( 6.4)
af_ever = 1 (%) 92662 (20.8)
pre_diagnoses_angina = 1 (%) 50115 (11.3)
post_diagnoses_angina = 1 (%) 6096 ( 1.4)
angina_ever = 1 (%) 56484 (12.7)
pre_diagnoses_anxiety_disorders = 1 (%) 67688 (15.2)
post_diagnoses_anxiety_disorders = 1 (%) 10556 ( 2.4)
anxiety_disorders_ever = 1 (%) 78961 (17.7)
pre_diagnoses_falls = 1 (%) 112934 (25.4)
post_diagnoses_falls = 1 (%) 125063 (28.1)
falls_ever = 1 (%) 240530 (54.0)
pre_diagnoses_fh_diabetes = 1 (%) 91133 (20.5)
post_diagnoses_fh_diabetes = 1 (%) 5686 ( 1.3)
fh_diabetes_ever = 1 (%) 97025 (21.8)
heartfailure_ever = 1 (%) 53881 (12.1)
pre_diagnoses_lowerlimbfracture = 1 (%) 54605 (12.3)
post_diagnoses_lowerlimbfracture = 1 (%) 32899 ( 7.4)
lowerlimbfracture_ever = 1 (%) 88292 (19.8)
pre_diagnoses_myocardialinfarction = 1 (%) 34853 ( 7.8)
post_diagnoses_myocardialinfarction = 1 (%) 6998 ( 1.6)
myocardialinfarction_ever = 1 (%) 42171 ( 9.5)
pre_diagnoses_qof_diabetes = 1 (%) 60791 (13.7)
post_diagnoses_qof_diabetes = 1 (%) 24661 ( 5.5)
qof_diabetes_ever = 1 (%) 86481 (19.4)
pre_diagnoses_revasc = 1 (%) 24090 ( 5.4)
post_diagnoses_revasc = 1 (%) 1104 ( 0.2)
revasc_ever = 1 (%) 25259 ( 5.7)
pre_diagnoses_stroke = 1 (%) 48354 (10.9)
post_diagnoses_stroke = 1 (%) 20314 ( 4.6)
stroke_ever = 1 (%) 70378 (15.8)
pre_diagnoses_tia = 1 (%) 38225 ( 8.6)
post_diagnoses_tia = 1 (%) 12286 ( 2.8)
tia_ever = 1 (%) 51115 (11.5)
alcohol_cat (%)
Excess 23239 ( 5.2)
Harmful 11657 ( 2.6)
None 41673 ( 9.4)
Unknown 118172 (26.5)
Within limits 250591 (56.3)
smoking_cat (%)
Active smoker 35954 ( 8.1)
Ex-smoker 185210 (41.6)
Non-smoker 142187 (31.9)
Unknown 81981 (18.4)
qrisk2_smoking_cat (%)
0 191562 (43.0)
1 116583 (26.2)
2 34441 ( 7.7)
3 1163 ( 0.3)
4 876 ( 0.2)
Unknown 100707 (22.6)
qrisk2_smoking_cat_uncoded (%)
Ex-smoker 116583 (26.2)
Heavy smoker 876 ( 0.2)
Light smoker 34441 ( 7.7)
Moderate smoker 1163 ( 0.3)
Non-smoker 191562 (43.0)
Unknown 100707 (22.6)
gp_qrisk2_ethnicity (%)
Bangladeshi 716 ( 0.2)
Black African 1358 ( 0.3)
Black Caribbean 5553 ( 1.2)
Chinese 449 ( 0.1)
Indian 4048 ( 0.9)
Other 3587 ( 0.8)
Other Asian 1575 ( 0.4)
Pakistani 1651 ( 0.4)
Unknown 112463 (25.3)
White 313932 (70.5)
hes_qrisk2_ethnicity (%)
Bangladeshi 616 ( 0.1)
Black African 1304 ( 0.3)
Black Caribbean 5520 ( 1.2)
Chinese 514 ( 0.1)
Indian 3784 ( 0.8)
Other 4954 ( 1.1)
Other Asian 1600 ( 0.4)
Pakistani 1516 ( 0.3)
Unknown 32537 ( 7.3)
White 392987 (88.2)
gp_5cat_ethnicity (%)
Black 7622 ( 1.7)
Mixed 1302 ( 0.3)
Other 2023 ( 0.5)
South Asian 8064 ( 1.8)
Unknown 112373 (25.2)
White 313948 (70.5)
hes_5cat_ethnicity (%)
Black 7829 ( 1.8)
Mixed 1031 ( 0.2)
Other 3432 ( 0.8)
South Asian 7516 ( 1.7)
Unknown 32537 ( 7.3)
White 392987 (88.2)
gp_16cat_ethnicity (%)
African 1371 ( 0.3)
Bangladeshi 716 ( 0.2)
Caribbean 5581 ( 1.3)
Chinese 451 ( 0.1)
Indian 4052 ( 0.9)
Other 1590 ( 0.4)
Other Asian 1585 ( 0.4)
Other Black 598 ( 0.1)
Other Mixed 341 ( 0.1)
Other White 9380 ( 2.1)
Pakistani 1652 ( 0.4)
Unknown 112728 (25.3)
White and Asian 165 ( 0.0)
White and Black African 200 ( 0.0)
White and Black Caribbean 612 ( 0.1)
White British 299235 (67.2)
White Irish 5075 ( 1.1)
hes_16cat_ethnicity (%)
African 1304 ( 0.3)
Bangladeshi 616 ( 0.1)
Caribbean 5520 ( 1.2)
Chinese 514 ( 0.1)
Indian 3784 ( 0.8)
Other 2918 ( 0.7)
Other Asian 1600 ( 0.4)
Other Black 1005 ( 0.2)
Other Mixed 1031 ( 0.2)
Pakistani 1516 ( 0.3)
Unknown 32537 ( 7.3)
White British 392987 (88.2)
pre_diagnoses_deep_vein_thrombosis = 1 (%) 20090 ( 4.5)
post_diagnoses_deep_vein_thrombosis = 1 (%) 8514 ( 1.9)
deep_vein_thrombosis_ever = 1 (%) 28825 ( 6.5)
pre_diagnoses_pulmonary_embolism = 1 (%) 10503 ( 2.4)
post_diagnoses_pulmonary_embolism = 1 (%) 4461 ( 1.0)
pulmonary_embolism_ever = 1 (%) 15125 ( 3.4)
VTE = 1 (%) 40338 ( 9.1)
Prescribed_3_months_before_obsdate = 1 (%) 88570 (19.9)
drug_name_3_months_before (%)
amisulpride 3714 ( 4.2)
aripiprazole 1447 ( 1.6)
benperidol 120 ( 0.1)
chlorpromazine 893 ( 1.0)
clozapine 16 ( 0.0)
flupentixol 300 ( 0.3)
fluphenazine 14 ( 0.0)
haloperidol 20194 (22.8)
levomepromazine 16302 (18.4)
lurasidone 2 ( 0.0)
olanzapine 5305 ( 6.0)
paliperidone 1 ( 0.0)
pericyazine 127 ( 0.1)
perphenazine 34 ( 0.0)
pimozide 988 ( 1.1)
prochlorperazine 16259 (18.4)
promazine 4246 ( 4.8)
quetiapine 17203 (19.4)
sulpiride 661 ( 0.7)
thioridazine 11 ( 0.0)
trifluoperazine 639 ( 0.7)
zuclopenthixol 94 ( 0.1)
Prescribed_6_months_before_obsdate = 1 (%) 91977 (20.7)
drug_name_6_months_before (%)
amisulpride 4000 ( 3.9)
aripiprazole 1549 ( 1.5)
benperidol 126 ( 0.1)
chlorpromazine 1095 ( 1.1)
clozapine 20 ( 0.0)
flupentixol 470 ( 0.5)
fluphenazine 21 ( 0.0)
haloperidol 21135 (20.4)
levomepromazine 16407 (15.8)
lurasidone 2 ( 0.0)
olanzapine 6522 ( 6.3)
paliperidone 1 ( 0.0)
pericyazine 149 ( 0.1)
perphenazine 46 ( 0.0)
pimozide 1825 ( 1.8)
prochlorperazine 25309 (24.4)
promazine 4677 ( 4.5)
quetiapine 18618 (18.0)
sulpiride 763 ( 0.7)
thioridazine 23 ( 0.0)
trifluoperazine 803 ( 0.8)
zuclopenthixol 101 ( 0.1)
Prescribed_12_months_before_obsdate = 1 (%) 97193 (21.8)
drug_name_12_months_before (%)
amisulpride 3903 ( 4.0)
aripiprazole 1525 ( 1.6)
benperidol 125 ( 0.1)
chlorpromazine 1033 ( 1.1)
clozapine 18 ( 0.0)
flupentixol 379 ( 0.4)
fluphenazine 17 ( 0.0)
haloperidol 21041 (21.6)
levomepromazine 16428 (16.9)
lurasidone 2 ( 0.0)
olanzapine 5884 ( 6.1)
paliperidone 1 ( 0.0)
pericyazine 145 ( 0.1)
perphenazine 43 ( 0.0)
pimozide 1192 ( 1.2)
prochlorperazine 21088 (21.7)
promazine 4576 ( 4.7)
quetiapine 18208 (18.7)
sulpiride 723 ( 0.7)
thioridazine 16 ( 0.0)
trifluoperazine 748 ( 0.8)
zuclopenthixol 98 ( 0.1)
Prescribed_after_obsdate = 1 (%) 81852 (18.4)
drug_name_after_obsdate (%)
amisulpride 3371 ( 4.1)
aripiprazole 1347 ( 1.6)
benperidol 110 ( 0.1)
chlorpromazine 752 ( 0.9)
clozapine 13 ( 0.0)
flupentixol 249 ( 0.3)
fluphenazine 12 ( 0.0)
haloperidol 18898 (23.1)
levomepromazine 16020 (19.6)
lurasidone 2 ( 0.0)
olanzapine 4776 ( 5.8)
paliperidone 1 ( 0.0)
pericyazine 111 ( 0.1)
perphenazine 28 ( 0.0)
pimozide 907 ( 1.1)
prochlorperazine 14486 (17.7)
promazine 3776 ( 4.6)
quetiapine 15757 (19.3)
sulpiride 590 ( 0.7)
thioridazine 8 ( 0.0)
trifluoperazine 557 ( 0.7)
zuclopenthixol 81 ( 0.1)
0 1
0 120214 101933
1 33604 189581
0 1
0 359064 15890
1 29852 40526
Black Mixed Other South Asian Unknown White
Black 6025 248 256 108 562 423
Mixed 537 93 123 102 113 334
Other 48 34 528 155 210 1048
South Asian 113 99 491 6331 661 369
Unknown 766 189 583 604 9353 100878
White 340 368 1451 216 21638 289935
strata median lower upper
1 gender_decode=F 3.400411 3.383984 3.419576
2 gender_decode=M 2.956879 2.937714 2.978782
strata median lower upper
1 age_category=65 - 74 5.448323 5.388090 5.505818
2 age_category=75 - 84 3.780972 3.759069 3.802875
3 age_category=85 - 94 2.299795 2.283368 2.316222
4 age_category=95+ 1.237509 1.199179 1.275838
Risperidone incident cohort
Overall
n 30060
diagnosedbeforeRegistration = 1 (%) 17005 (56.6)
died = 1 (%) 17390 (57.9)
death_composite = 1 (%) 23726 (78.9)
ONS_died = 1 (%) 20695 (68.8)
age_diagnosis (mean (SD)) 80.44 (7.13)
age_risperidone (mean (SD)) 82.99 (6.87)
deprivation (%)
1 6726 (22.4)
2 7388 (24.6)
3 6070 (20.2)
4 5181 (17.3)
5 4657 (15.5)
gender_decode = M (%) 11635 (38.7)
GP_stroke = 1 (%) 4214 (14.0)
HES_stroke = 1 (%) 3204 (10.7)
stroke_composite = 1 (%) 5161 (17.2)
primary_death_stroke = 1 (%) 785 ( 2.6)
Composite_pre_stroke = 1 (%) 4237 (14.1)
Composite_post_stroke = 1 (%) 1695 ( 5.6)
comorbidity_stroke = 1 (%) 4214 (14.0)
pre_index_date_stroke = 1 (%) 3609 (12.0)
post_index_date_stroke = 1 (%) 1061 ( 3.5)
Stroke_prior_to_risperidone = 1 (%) 4237 (14.1)
Stroke__within_year_after_1st_risperidone_presc = 1 (%) 1094 ( 3.6)
death_in_a_year_after_risperidone = 1 (%) 8585 (28.6)
sex = 1 (%) 11635 (38.7)
ethnicity (%)
Black 504 ( 1.7)
Mixed 107 ( 0.4)
Other 171 ( 0.6)
South Asian 490 ( 1.6)
Unknown 512 ( 1.7)
White 28276 (94.1)
age_category (%)
65 - 74 6544 (21.8)
75 - 84 14552 (48.4)
85+ 8964 (29.8)
year_of_diagnosis (%)
2004 1192 ( 4.0)
2005 1008 ( 3.4)
2006 1068 ( 3.6)
2007 1063 ( 3.5)
2008 1191 ( 4.0)
2009 1532 ( 5.1)
2010 1922 ( 6.4)
2011 2071 ( 6.9)
2012 2258 ( 7.5)
2013 2462 ( 8.2)
2014 2540 ( 8.4)
2015 2284 ( 7.6)
2016 2048 ( 6.8)
2017 1986 ( 6.6)
2018 1709 ( 5.7)
2019 1412 ( 4.7)
2020 1089 ( 3.6)
2021 678 ( 2.3)
2022 436 ( 1.5)
2023 111 ( 0.4)
year_of_prescription (%)
2004 661 ( 2.2)
2005 444 ( 1.5)
2006 567 ( 1.9)
2007 628 ( 2.1)
2008 510 ( 1.7)
2009 613 ( 2.0)
2010 1163 ( 3.9)
2011 1417 ( 4.7)
2012 1632 ( 5.4)
2013 1910 ( 6.4)
2014 2201 ( 7.3)
2015 2452 ( 8.2)
2016 2549 ( 8.5)
2017 2583 ( 8.6)
2018 2389 ( 7.9)
2019 2326 ( 7.7)
2020 2436 ( 8.1)
2021 1598 ( 5.3)
2022 1195 ( 4.0)
2023 786 ( 2.6)
stroke_3_months_prior = 1 (%) 155 ( 0.5)
stroke_6_months_prior = 1 (%) 232 ( 0.8)
stroke_12_months_prior = 1 (%) 368 ( 1.2)
prescribed_BMJ_antipsyc_drug = 1 (%) 25732 (85.6)
stroke_recency_cat (%)
<= 1 368 (10.2)
> 7 3042 (84.3)
1 - 2 146 ( 4.0)
2 - 3 49 ( 1.4)
3 - 4 4 ( 0.1)
dementia_duration_prior_risperidone (mean (SD)) 2.11 (2.35)
Survival_time (mean (SD)) 1.74 (1.90)
comorbidity_af = 1 (%) 5331 (17.7)
pre_index_date_af = 1 (%) 4765 (15.9)
post_index_date_af = 1 (%) 1791 ( 6.0)
comorbidity_angina = 1 (%) 3625 (12.1)
pre_index_date_angina = 1 (%) 3536 (11.8)
post_index_date_angina = 1 (%) 343 ( 1.1)
comorbidity_anxiety_disorders = 1 (%) 6185 (20.6)
pre_index_date_anxiety_disorders = 1 (%) 5937 (19.8)
post_index_date_anxiety_disorders = 1 (%) 674 ( 2.2)
comorbidity_falls = 1 (%) 16777 (55.8)
pre_index_date_falls = 1 (%) 12080 (40.2)
post_index_date_falls = 1 (%) 8833 (29.4)
comorbidity_fh_diabetes = 1 (%) 6018 (20.0)
pre_index_date_fh_diabetes = 1 (%) 5927 (19.7)
post_index_date_fh_diabetes = 1 (%) 130 ( 0.4)
comorbidity_fh_premature_cvd = 1 (%) 2311 ( 7.7)
pre_index_date_fh_premature_cvd = 1 (%) 2279 ( 7.6)
post_index_date_fh_premature_cvd = 1 (%) 46 ( 0.2)
comorbidity_heartfailure = 1 (%) 2683 ( 8.9)
pre_index_date_heartfailure = 1 (%) 2276 ( 7.6)
post_index_date_heartfailure = 1 (%) 906 ( 3.0)
comorbidity_lowerlimbfracture = 1 (%) 6301 (21.0)
pre_index_date_lowerlimbfracture = 1 (%) 4757 (15.8)
post_index_date_lowerlimbfracture = 1 (%) 1943 ( 6.5)
comorbidity_myocardialinfarction = 1 (%) 2602 ( 8.7)
pre_index_date_myocardialinfarction = 1 (%) 2450 ( 8.2)
post_index_date_myocardialinfarction = 1 (%) 279 ( 0.9)
comorbidity_qof_diabetes = 1 (%) 5484 (18.2)
pre_index_date_qof_diabetes = 1 (%) 5167 (17.2)
post_index_date_qof_diabetes = 1 (%) 2386 ( 7.9)
comorbidity_revasc = 1 (%) 1608 ( 5.3)
pre_index_date_revasc = 1 (%) 1599 ( 5.3)
post_index_date_revasc = 1 (%) 24 ( 0.1)
comorbidity_tia = 1 (%) 3250 (10.8)
pre_index_date_tia = 1 (%) 2791 ( 9.3)
post_index_date_tia = 1 (%) 701 ( 2.3)
comorbidity_deep_vein_thrombosis = 1 (%) 1989 ( 6.6)
pre_index_date_deep_vein_thrombosis = 1 (%) 1528 ( 5.1)
post_index_date_deep_vein_thrombosis = 1 (%) 549 ( 1.8)
comorbidity_haem_cancer = 1 (%) 665 ( 2.2)
pre_index_date_haem_cancer = 1 (%) 573 ( 1.9)
post_index_date_haem_cancer = 1 (%) 186 ( 0.6)
comorbidity_pulmonary_embolism = 1 (%) 978 ( 3.3)
pre_index_date_pulmonary_embolism = 1 (%) 752 ( 2.5)
post_index_date_pulmonary_embolism = 1 (%) 271 ( 0.9)
comorbidity_solid_cancer = 1 (%) 5148 (17.1)
pre_index_date_solid_cancer = 1 (%) 4708 (15.7)
post_index_date_solid_cancer = 1 (%) 1065 ( 3.5)
VTE = 1 (%) 2743 ( 9.1)
BMI (%)
Normal 10802 (35.9)
Obesity 3879 (12.9)
Overweight 8591 (28.6)
Severely Obese 278 ( 0.9)
Underweight 1303 ( 4.3)
Unknown 5207 (17.3)
totalcholesterol (%)
< 160 mg/dl 6657 (22.1)
> 280 mg/dl 1042 ( 3.5)
199 mg/dl 7480 (24.9)
200 - 239 mg/dl 6438 (21.4)
240 - 279 mg/dl 2810 ( 9.3)
Unknown 5633 (18.7)
testvalue_dbp (mean (SD)) 76.41 (11.77)
testvalue_sbp (mean (SD)) 135.80 (20.25)
testvalue_totalcholesterol (mean (SD)) 4.98 (1.24)
gp_5cat_ethnicity (%)
Black 444 ( 1.5)
Mixed 90 ( 0.3)
Other 147 ( 0.5)
South Asian 449 ( 1.5)
Unknown 7311 (24.3)
White 21619 (71.9)
gp_16cat_ethnicity (%)
African 75 ( 0.2)
Bangladeshi 33 ( 0.1)
Caribbean 321 ( 1.1)
Chinese 21 ( 0.1)
Indian 227 ( 0.8)
Other 128 ( 0.4)
Other Asian 83 ( 0.3)
Other Black 47 ( 0.2)
Other Mixed 21 ( 0.1)
Other White 665 ( 2.2)
Pakistani 101 ( 0.3)
Unknown 7332 (24.4)
White and Asian 16 ( 0.1)
White and Black African 11 ( 0.0)
White and Black Caribbean 40 ( 0.1)
White British 20623 (68.6)
White Irish 316 ( 1.1)
gp_qrisk2_ethnicity (%)
Bangladeshi 33 ( 0.1)
Black African 75 ( 0.2)
Black Caribbean 319 ( 1.1)
Chinese 21 ( 0.1)
Indian 227 ( 0.8)
Other 265 ( 0.9)
Other Asian 82 ( 0.3)
Pakistani 101 ( 0.3)
Unknown 7318 (24.3)
White 21619 (71.9)
alcohol_cat (%)
Excess 1467 ( 4.9)
Harmful 818 ( 2.7)
None 2220 ( 7.4)
Unknown 10576 (35.2)
Within limits 14979 (49.8)
smoking_cat (%)
Active smoker 2069 ( 6.9)
Ex-smoker 11224 (37.3)
Non-smoker 8404 (28.0)
Unknown 8363 (27.8)
qrisk2_smoking_cat (%)
0 11101 (36.9)
1 7373 (24.5)
2 2037 ( 6.8)
3 75 ( 0.2)
4 40 ( 0.1)
Unknown 9434 (31.4)
qrisk2_smoking_cat_uncoded (%)
Ex-smoker 7373 (24.5)
Heavy smoker 40 ( 0.1)
Light smoker 2037 ( 6.8)
Moderate smoker 75 ( 0.2)
Non-smoker 11101 (36.9)
Unknown 9434 (31.4)
drug_name (%)
amisulpride 488 ( 3.2)
aripiprazole 198 ( 1.3)
benperidol 20 ( 0.1)
chlorpromazine 230 ( 1.5)
clozapine 1 ( 0.0)
flupentixol 165 ( 1.1)
fluphenazine 12 ( 0.1)
haloperidol 2714 (17.8)
levomepromazine 1697 (11.1)
olanzapine 1106 ( 7.2)
pericyazine 31 ( 0.2)
perphenazine 11 ( 0.1)
pimozide 128 ( 0.8)
prochlorperazine 6004 (39.3)
promazine 517 ( 3.4)
quetiapine 1798 (11.8)
sulpiride 38 ( 0.2)
thioridazine 34 ( 0.2)
trifluoperazine 78 ( 0.5)
zuclopenthixol 14 ( 0.1)
frailty (%)
Mild 1358 ( 4.5)
Moderate 3435 (11.4)
Severe 5376 (17.9)
Unknown 19891 (66.2)
year_diagnosis_cat (%)
> 2020 1225 ( 4.1)
2004 - 2008 5522 (18.4)
2009 - 2012 7783 (25.9)
2013 - 2016 9334 (31.1)
2017 - 2020 6196 (20.6)
prescribed_other_antipsyc_drug = 1 (%) 15284 (50.8)
pre_indexdate_antipysch_prescr = 1 (%) 10105 (66.1)
post_indexdate_antipysch_prescr = 1 (%) 5088 (33.3)
same_indexdate_antipysch_prescr = 1 (%) 91 ( 0.6)
pre_indexdate_drug_name (%)
amisulpride 184 ( 1.8)
aripiprazole 76 ( 0.8)
benperidol 7 ( 0.1)
chlorpromazine 123 ( 1.2)
clozapine 1 ( 0.0)
flupentixol 196 ( 1.9)
fluphenazine 11 ( 0.1)
haloperidol 915 ( 9.1)
levomepromazine 91 ( 0.9)
olanzapine 584 ( 5.8)
pericyazine 19 ( 0.2)
perphenazine 7 ( 0.1)
pimozide 118 ( 1.2)
prochlorperazine 6005 (59.4)
promazine 316 ( 3.1)
quetiapine 1179 (11.7)
sulpiride 42 ( 0.4)
thioridazine 105 ( 1.0)
trifluoperazine 119 ( 1.2)
zuclopenthixol 7 ( 0.1)
same_indexdate_drug_name (%)
amisulpride 2 ( 2.2)
aripiprazole 8 ( 8.8)
chlorpromazine 5 ( 5.5)
flupentixol 2 ( 2.2)
haloperidol 21 (23.1)
levomepromazine 1 ( 1.1)
olanzapine 3 ( 3.3)
pimozide 8 ( 8.8)
prochlorperazine 6 ( 6.6)
promazine 15 (16.5)
quetiapine 17 (18.7)
trifluoperazine 3 ( 3.3)
post_indexdate_drug_name (%)
amisulpride 118 ( 2.3)
aripiprazole 174 ( 3.4)
benperidol 3 ( 0.1)
chlorpromazine 30 ( 0.6)
flupentixol 12 ( 0.2)
haloperidol 1422 (27.9)
levomepromazine 1562 (30.7)
olanzapine 460 ( 9.0)
pericyazine 5 ( 0.1)
pimozide 35 ( 0.7)
prochlorperazine 327 ( 6.4)
promazine 136 ( 2.7)
quetiapine 762 (15.0)
sulpiride 16 ( 0.3)
trifluoperazine 20 ( 0.4)
zuclopenthixol 6 ( 0.1)
care_home = 1 (%) 12371 (41.2)
care_home_before_indexdate = 1 (%) 3977 (32.1)
care_home_at_indexdate = 1 (%) 127 ( 1.0)
care_home_90_days_after_indexdate = 1 (%) 2683 (21.7)
TimeSinceFirstPrescription (mean (SD)) 0.49 (0.93)
Prescription_ever_cat (%)
>100 555 ( 1.8)
1 5163 (17.2)
10 781 ( 2.6)
11 - 20 5103 (17.0)
2 2655 ( 8.8)
21 - 30 2757 ( 9.2)
3 1930 ( 6.4)
31 - 40 1618 ( 5.4)
4 1582 ( 5.3)
41 - 50 1002 ( 3.3)
5 1303 ( 4.3)
51 - 100 1653 ( 5.5)
6 1111 ( 3.7)
7 1051 ( 3.5)
8 926 ( 3.1)
9 870 ( 2.9)
Prescriptions_after_a_year_cat (%)
>100 301 ( 3.0)
1 699 ( 7.0)
10 288 ( 2.9)
11 - 20 2119 (21.3)
2 610 ( 6.1)
21 - 30 1193 (12.0)
3 520 ( 5.2)
31 - 40 759 ( 7.6)
4 455 ( 4.6)
41 - 50 469 ( 4.7)
5 413 ( 4.2)
51 - 100 723 ( 7.3)
6 372 ( 3.7)
7 373 ( 3.8)
8 328 ( 3.3)
9 311 ( 3.1)
Prescriptions_within_a_year_cat (%)
>100 16 ( 0.1)
1 5382 (17.9)
10 953 ( 3.2)
11 - 20 9427 (31.4)
2 2739 ( 9.1)
21 - 30 850 ( 2.8)
3 2004 ( 6.7)
31 - 40 310 ( 1.0)
4 1651 ( 5.5)
41 - 50 298 ( 1.0)
5 1392 ( 4.6)
51 - 100 517 ( 1.7)
6 1232 ( 4.1)
7 1224 ( 4.1)
8 1064 ( 3.5)
9 1001 ( 3.3)
consultation_counts_Cat (%)
0 - 50 10847 (36.7)
101 - 150 5102 (17.2)
151 - 200 1936 ( 6.5)
201 - 250 732 ( 2.5)
251 - 300 302 ( 1.0)
301 - 350 123 ( 0.4)
351 - 400 50 ( 0.2)
401 - 450 34 ( 0.1)
451 - 500 28 ( 0.1)
501 - 800 30 ( 0.1)
51 - 100 10391 (35.1)
801 - 1000 3 ( 0.0)
pre_BMJ_indexdate_drug_name (%)
amisulpride 169 ( 8.7)
aripiprazole 15 ( 0.8)
benperidol 7 ( 0.4)
chlorpromazine 122 ( 6.3)
clozapine 1 ( 0.1)
flupentixol 122 ( 6.3)
fluphenazine 10 ( 0.5)
haloperidol 852 (43.7)
levomepromazine 10 ( 0.5)
olanzapine 49 ( 2.5)
pericyazine 19 ( 1.0)
perphenazine 2 ( 0.1)
pimozide 5 ( 0.3)
prochlorperazine 368 (18.9)
promazine 46 ( 2.4)
quetiapine 67 ( 3.4)
sulpiride 16 ( 0.8)
thioridazine 33 ( 1.7)
trifluoperazine 34 ( 1.7)
zuclopenthixol 2 ( 0.1)
same_BMJ_indexdate_drug_name (%)
amisulpride 93 ( 0.9)
aripiprazole 186 ( 1.8)
benperidol 3 ( 0.0)
chlorpromazine 30 ( 0.3)
flupentixol 64 ( 0.6)
fluphenazine 1 ( 0.0)
haloperidol 1187 (11.4)
levomepromazine 1289 (12.3)
olanzapine 770 ( 7.4)
pericyazine 5 ( 0.0)
perphenazine 5 ( 0.0)
pimozide 128 ( 1.2)
prochlorperazine 4808 (46.0)
promazine 309 ( 3.0)
quetiapine 1400 (13.4)
sulpiride 29 ( 0.3)
thioridazine 59 ( 0.6)
trifluoperazine 75 ( 0.7)
zuclopenthixol 6 ( 0.1)
post_BMJ_indexdate_drug_name (%)
amisulpride 34 ( 3.8)
aripiprazole 28 ( 3.1)
chlorpromazine 5 ( 0.6)
flupentixol 9 ( 1.0)
haloperidol 150 (16.8)
levomepromazine 89 (10.0)
olanzapine 66 ( 7.4)
pimozide 7 ( 0.8)
prochlorperazine 320 (35.9)
promazine 26 ( 2.9)
quetiapine 135 (15.2)
sulpiride 5 ( 0.6)
thioridazine 2 ( 0.2)
trifluoperazine 12 ( 1.3)
zuclopenthixol 3 ( 0.3)
comorbidity_hypertension (%)
Elevated 3327 (11.1)
Normal 4156 (13.8)
Stage 1 13285 (44.2)
Stage 2 8633 (28.7)
Stage 3 (severe) 191 ( 0.6)
Unknown 468 ( 1.6)
pre_index_date_hypertension = 1 (%) 24666 (83.3)
comorbidity_hearing_loss = 1 (%) 8411 (28.0)
pre_index_date_hearing_loss = 1 (%) 7900 (26.3)
post_index_date_hearing_loss = 1 (%) 1127 ( 3.7)
pre_indexdate_BMJ_antipysch_prescr = 1 (%) 1961 ( 7.6)
post_indexdate_BMJ_antipysch_prescr = 1 (%) 1756 ( 6.8)
same_indexdate_BMJ_antipysch_prescr = 1 (%) 22015 (85.6)
HES_comorbidity_stroke = 1 (%) 3204 (10.7)
HES_pre_index_date_stroke = 1 (%) 2568 ( 8.5)
HES_post_index_date_stroke = 1 (%) 964 ( 3.2)
hes_5cat_ethnicity (%)
Black 474 ( 1.6)
Mixed 70 ( 0.2)
Other 189 ( 0.6)
South Asian 440 ( 1.5)
Unknown 2169 ( 7.2)
White 26718 (88.9)
hes_16cat_ethnicity (%)
African 78 ( 0.3)
Bangladeshi 30 ( 0.1)
Caribbean 341 ( 1.1)
Chinese 20 ( 0.1)
Indian 202 ( 0.7)
Other 169 ( 0.6)
Other Asian 106 ( 0.4)
Other Black 55 ( 0.2)
Other Mixed 70 ( 0.2)
Pakistani 102 ( 0.3)
Unknown 2169 ( 7.2)
White British 26718 (88.9)
hes_qrisk2_ethnicity (%)
Bangladeshi 30 ( 0.1)
Black African 78 ( 0.3)
Black Caribbean 341 ( 1.1)
Chinese 20 ( 0.1)
Indian 202 ( 0.7)
Other 294 ( 1.0)
Other Asian 106 ( 0.4)
Pakistani 102 ( 0.3)
Unknown 2169 ( 7.2)
White 26718 (88.9)
strata median lower upper
1 gender_decode=F 4.654346 4.591376 4.717317
2 gender_decode=M 4.101300 4.035592 4.175222
strata median lower upper
1 age_category=65 - 74 6.308008 6.179329 6.461328
2 age_category=75 - 84 4.692676 4.624230 4.761123
3 age_category=85+ 3.063655 2.997947 3.126626
COX model
Call:
coxph(formula = Surv(Survival_time, Composite_post_stroke) ~
age_diagnosis + Composite_pre_stroke + sex, data = CompleteData)
n= 30060, number of events= 1695
coef exp(coef) se(coef) z Pr(>|z|)
age_diagnosis 0.006682 1.006704 0.003562 1.876 0.0607 .
Composite_pre_stroke1 1.825286 6.204567 0.049282 37.038 <2e-16 ***
sex1 0.119763 1.127229 0.051070 2.345 0.0190 *
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
age_diagnosis 1.007 0.9933 0.9997 1.014
Composite_pre_stroke1 6.205 0.1612 5.6333 6.834
sex1 1.127 0.8871 1.0199 1.246
Concordance= 0.713 (se = 0.008 )
Likelihood ratio test= 1204 on 3 df, p=<2e-16
Wald test = 1419 on 3 df, p=<2e-16
Score (logrank) test = 1860 on 3 df, p=<2e-16
One year censoring
Call:
coxph(formula = Surv(Survival_time, Composite_post_stroke) ~
age_diagnosis + Composite_pre_stroke + sex, data = CensoringData_1year)
n= 30040, number of events= 1037
(20 observations deleted due to missingness)
coef exp(coef) se(coef) z Pr(>|z|)
age_diagnosis 0.003332 1.003337 0.004501 0.740 0.4592
Composite_pre_stroke1 2.076755 7.978539 0.062823 33.057 <2e-16 ***
sex1 0.124871 1.133003 0.064246 1.944 0.0519 .
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
age_diagnosis 1.003 0.9967 0.9945 1.012
Composite_pre_stroke1 7.979 0.1253 7.0542 9.024
sex1 1.133 0.8826 0.9990 1.285
Concordance= 0.726 (se = 0.009 )
Likelihood ratio test= 1019 on 3 df, p=<2e-16
Wald test = 1126 on 3 df, p=<2e-16
Score (logrank) test = 1597 on 3 df, p=<2e-16
Excluding stroke 3 months prior
Call:
coxph(formula = Surv(Survival_time, Composite_post_stroke) ~
age_diagnosis + Composite_pre_stroke + sex, data = Excluding_3_monthsPriorStroke)
n= 29905, number of events= 1615
coef exp(coef) se(coef) z Pr(>|z|)
age_diagnosis 0.007775 1.007806 0.003646 2.133 0.0330 *
Composite_pre_stroke1 1.743310 5.716231 0.050815 34.307 <2e-16 ***
sex1 0.121428 1.129108 0.052390 2.318 0.0205 *
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
age_diagnosis 1.008 0.9923 1.001 1.015
Composite_pre_stroke1 5.716 0.1749 5.174 6.315
sex1 1.129 0.8857 1.019 1.251
Concordance= 0.701 (se = 0.008 )
Likelihood ratio test= 1023 on 3 df, p=<2e-16
Wald test = 1223 on 3 df, p=<2e-16
Score (logrank) test = 1566 on 3 df, p=<2e-16
Excluding stroke 12 months prior
Call:
coxph(formula = Surv(Survival_time, Composite_post_stroke) ~
age_diagnosis + Composite_pre_stroke + sex, data = Excluding_12_monthsPriorStroke)
n= 29692, number of events= 1546
coef exp(coef) se(coef) z Pr(>|z|)
age_diagnosis 0.008703 1.008741 0.003734 2.331 0.0198 *
Composite_pre_stroke1 1.679211 5.361324 0.052382 32.057 <2e-16 ***
sex1 0.136316 1.146044 0.053538 2.546 0.0109 *
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
age_diagnosis 1.009 0.9913 1.001 1.016
Composite_pre_stroke1 5.361 0.1865 4.838 5.941
sex1 1.146 0.8726 1.032 1.273
Concordance= 0.689 (se = 0.008 )
Likelihood ratio test= 886 on 3 df, p=<2e-16
Wald test = 1073 on 3 df, p=<2e-16
Score (logrank) test = 1352 on 3 df, p=<2e-16
Matching
Updated Algorithm - exact match on: Sex, stroke history, cvd and risperidone age category (65-74, 75-84, 85+)
Stratified by risperidone
0 1 p test SMD
n 137031 28464
sex = 1 (%) 51780 (37.8) 10847 ( 38.1) 0.313 0.007
risperidone = 1 (%) 0 ( 0.0) 28464 (100.0) <0.001 NaN
age_risperidone (mean (SD)) 83.18 (6.82) 83.12 (6.83) 0.136 0.010
age_diagnosis (mean (SD)) 80.49 (6.90) 80.51 (7.10) 0.670 0.003
age_risperidone_cat (%) 0.163 0.012
65 - 74 15313 (11.2) 3290 ( 11.6)
75 - 84 61837 (45.1) 12823 ( 45.0)
85+ 59881 (43.7) 12351 ( 43.4)
care_home_before_indexdate = 1 (%) 17946 (13.1) 3734 ( 13.1) 0.928 0.001
deprivation (%) 0.895 0.008
1 30555 (22.3) 6379 ( 22.4)
2 33591 (24.5) 6942 ( 24.4)
3 27469 (20.0) 5764 ( 20.3)
4 23854 (17.4) 4908 ( 17.2)
5 21450 (15.7) 4444 ( 15.6)
Unknown 112 ( 0.1) 27 ( 0.1)
Stroke__within_year_after_1st_risperidone_presc = 1 (%) 4671 ( 3.4) 1112 ( 3.9) <0.001 0.027
stroke_composite_pre_index_date = 1 (%) 17986 (13.1) 3880 ( 13.6) 0.022 0.015
pre_index_date_angina = 1 (%) 16201 (11.8) 3344 ( 11.7) 0.730 0.002
pre_index_date_heartfailure = 1 (%) 10524 ( 7.7) 2199 ( 7.7) 0.802 0.002
BMI (%) 0.065 0.021
Missing 25440 (18.6) 5505 ( 19.3)
Normal 53314 (38.9) 11024 ( 38.7)
Obesity 14336 (10.5) 2973 ( 10.4)
Overweight 35122 (25.6) 7175 ( 25.2)
Severely Obese 916 ( 0.7) 189 ( 0.7)
Underweight 7903 ( 5.8) 1598 ( 5.6)
Prescribed_other_antipsychotic_Prior = 1 (%) 36951 (27.0) 7377 ( 25.9) <0.001 0.024
period_before_prescription (mean (SD)) 2.73 (2.19) 2.62 (2.40) <0.001 0.051
pre_index_date_myocardialinfarction = 1 (%) 11098 ( 8.1) 2316 ( 8.1) 0.841 0.001
pre_index_date_tia = 1 (%) 12915 ( 9.4) 2641 ( 9.3) 0.448 0.005
pre_index_date_falls = 1 (%) 57114 (41.7) 11748 ( 41.3) 0.208 0.008
pre_index_date_lowerlimbfracture = 1 (%) 21750 (15.9) 4536 ( 15.9) 0.796 0.002
pre_index_date_ihd = 1 (%) 22750 (16.6) 4717 ( 16.6) 0.908 0.001
pre_index_date_pad = 1 (%) 10688 ( 7.8) 2207 ( 7.8) 0.801 0.002
pre_index_date_af = 1 (%) 21971 (16.0) 4560 ( 16.0) 0.962 <0.001
pre_index_date_revasc = 1 (%) 7317 ( 5.3) 1514 ( 5.3) 0.899 0.001
pre_index_date_qof_diabetes = 1 (%) 24086 (17.6) 4979 ( 17.5) 0.739 0.002
pre_index_date_anxiety_disorders = 1 (%) 27219 (19.9) 5635 ( 19.8) 0.804 0.002
pre_index_date_fh_diabetes = 1 (%) 28736 (21.0) 5824 ( 20.5) 0.055 0.013
pre_index_date_fh_premature_cvd = 1 (%) 11011 ( 8.0) 2233 ( 7.8) 0.287 0.007
pre_index_date_pulmonary_embolism = 1 (%) 3447 ( 2.5) 728 ( 2.6) 0.695 0.003
pre_index_date_deep_vein_thrombosis = 1 (%) 6993 ( 5.1) 1468 ( 5.2) 0.717 0.002
pre_index_date_hearing_loss = 1 (%) 36712 (26.8) 7645 ( 26.9) 0.821 0.002
pre_index_date_VTE = 1 (%) 9634 ( 7.0) 2020 ( 7.1) 0.701 0.003
pre_index_date_haem_cancer = 1 (%) 2610 ( 1.9) 540 ( 1.9) 0.951 0.001
pre_index_date_solid_cancer = 1 (%) 21938 (16.0) 4517 ( 15.9) 0.563 0.004
pre_index_date_cvd = 1 (%) 54965 (40.1) 11454 ( 40.2) 0.691 0.003
comorbidity_hypertension (%) <0.001 0.043
Elevated 24085 (17.6) 4969 ( 17.5)
Normal 34822 (25.4) 7217 ( 25.4)
Stage 1 54077 (39.5) 11186 ( 39.3)
Stage 2 22495 (16.4) 4638 ( 16.3)
Stage 3 (severe) 205 ( 0.1) 39 ( 0.1)
Unknown 1347 ( 1.0) 415 ( 1.5)
Call:
coxph(formula = Surv(Survival_time, stroke_composite_post_index_date) ~
age_diagnosis + sex + stroke_composite_pre_index_date, data = table)
n= 149704, number of events= 9103
coef exp(coef) se(coef) z Pr(>|z|)
age_diagnosis 0.013596 1.013689 0.001622 8.383 < 2e-16 ***
sex 0.107951 1.113993 0.021935 4.921 8.59e-07 ***
stroke_composite_pre_index_date 1.823485 6.193406 0.021538 84.664 < 2e-16 ***
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
age_diagnosis 1.014 0.9865 1.010 1.017
sex 1.114 0.8977 1.067 1.163
stroke_composite_pre_index_date 6.193 0.1615 5.937 6.460
Concordance= 0.705 (se = 0.003 )
Likelihood ratio test= 6095 on 3 df, p=<2e-16
Wald test = 7502 on 3 df, p=<2e-16
Score (logrank) test = 9837 on 3 df, p=<2e-16
strata median lower upper
1 risperidone=0 5.661875 5.629021 5.697467
2 risperidone=1 4.558522 4.503765 4.613279
strata median lower upper
1 risperidone=0 7.093771 6.967830 7.233402
2 risperidone=1 5.314168 5.117043 5.489391
Updated Algorithm - without exact match
Stratified by risperidone
0 1 p test SMD
n 146209 29691
sex = 1 (%) 56211 ( 38.4) 11457 ( 38.6) 0.652 0.003
risperidone = 1 (%) 0 ( 0.0) 29691 (100.0) <0.001 NaN
age_risperidone (mean (SD)) 83.10 (6.88) 83.02 (6.86) 0.072 0.011
age_diagnosis (mean (SD)) 80.46 (6.92) 80.45 (7.12) 0.763 0.002
age_risperidone_cat (%) 0.320 0.010
65 - 74 17457 ( 11.9) 3578 ( 12.1)
75 - 84 65315 ( 44.7) 13372 ( 45.0)
85+ 63437 ( 43.4) 12741 ( 42.9)
care_home_before_indexdate = 1 (%) 20110 ( 13.8) 3926 ( 13.2) 0.015 0.016
deprivation (%) 0.874 0.009
1 32589 ( 22.3) 6648 ( 22.4)
2 36053 ( 24.7) 7285 ( 24.5)
3 29473 ( 20.2) 5987 ( 20.2)
4 24901 ( 17.0) 5124 ( 17.3)
5 23033 ( 15.8) 4617 ( 15.6)
Unknown 160 ( 0.1) 30 ( 0.1)
Stroke__within_year_after_1st_risperidone_presc = 0 (%) 146209 (100.0) 29691 (100.0) NA <0.001
stroke_composite_pre_index_date = 1 (%) 20802 ( 14.2) 4199 ( 14.1) 0.708 0.002
pre_index_date_angina = 1 (%) 17189 ( 11.8) 3513 ( 11.8) 0.721 0.002
pre_index_date_heartfailure = 1 (%) 11468 ( 7.8) 2267 ( 7.6) 0.227 0.008
BMI (%) 0.957 0.007
Missing 31664 ( 21.7) 6381 ( 21.5)
Normal 54821 ( 37.5) 11214 ( 37.8)
Obesity 14961 ( 10.2) 3008 ( 10.1)
Overweight 35797 ( 24.5) 7267 ( 24.5)
Severely Obese 958 ( 0.7) 193 ( 0.7)
Underweight 8008 ( 5.5) 1628 ( 5.5)
Prescribed_other_antipsychotic_Prior = 1 (%) 37749 ( 25.8) 7442 ( 25.1) 0.007 0.017
period_before_prescription (mean (SD)) 2.67 (2.15) 2.57 (2.39) <0.001 0.043
pre_index_date_myocardialinfarction = 1 (%) 12031 ( 8.2) 2425 ( 8.2) 0.735 0.002
pre_index_date_tia = 1 (%) 13602 ( 9.3) 2778 ( 9.4) 0.782 0.002
pre_index_date_falls = 1 (%) 60023 ( 41.1) 12018 ( 40.5) 0.067 0.012
pre_index_date_lowerlimbfracture = 1 (%) 23439 ( 16.0) 4718 ( 15.9) 0.552 0.004
pre_index_date_ihd = 1 (%) 24382 ( 16.7) 4941 ( 16.6) 0.890 0.001
pre_index_date_pad = 1 (%) 11169 ( 7.6) 2287 ( 7.7) 0.716 0.002
pre_index_date_af = 1 (%) 23246 ( 15.9) 4726 ( 15.9) 0.945 <0.001
pre_index_date_revasc = 1 (%) 7879 ( 5.4) 1588 ( 5.3) 0.789 0.002
pre_index_date_qof_diabetes = 1 (%) 25218 ( 17.2) 5127 ( 17.3) 0.941 0.001
pre_index_date_anxiety_disorders = 1 (%) 28992 ( 19.8) 5874 ( 19.8) 0.864 0.001
pre_index_date_fh_diabetes = 1 (%) 29469 ( 20.2) 5900 ( 19.9) 0.269 0.007
pre_index_date_fh_premature_cvd = 1 (%) 11364 ( 7.8) 2269 ( 7.6) 0.451 0.005
pre_index_date_pulmonary_embolism = 1 (%) 3762 ( 2.6) 751 ( 2.5) 0.679 0.003
pre_index_date_deep_vein_thrombosis = 1 (%) 7527 ( 5.1) 1515 ( 5.1) 0.757 0.002
pre_index_date_hearing_loss = 1 (%) 38623 ( 26.4) 7856 ( 26.5) 0.884 0.001
pre_index_date_VTE = 1 (%) 10399 ( 7.1) 2088 ( 7.0) 0.633 0.003
pre_index_date_haem_cancer = 1 (%) 2787 ( 1.9) 567 ( 1.9) 0.987 <0.001
pre_index_date_solid_cancer = 1 (%) 22971 ( 15.7) 4665 ( 15.7) 1.000 <0.001
pre_index_date_cvd = 1 (%) 59298 ( 40.6) 12046 ( 40.6) 0.969 <0.001
comorbidity_hypertension (%) <0.001 0.043
Elevated 24970 ( 17.1) 5076 ( 17.1)
Normal 37629 ( 25.7) 7494 ( 25.2)
Stage 1 56282 ( 38.5) 11372 ( 38.3)
Stage 2 23109 ( 15.8) 4678 ( 15.8)
Stage 3 (severe) 204 ( 0.1) 40 ( 0.1)
Unknown 4015 ( 2.7) 1031 ( 3.5)
Call:
coxph(formula = Surv(Survival_time, stroke_composite_post_index_date) ~
risperidone, data = table)
n= 176012, number of events= 11632
coef exp(coef) se(coef) z Pr(>|z|)
risperidone 0.06783 1.07018 0.02643 2.567 0.0103 *
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
risperidone 1.07 0.9344 1.016 1.127
Concordance= 0.509 (se = 0.002 )
Likelihood ratio test= 6.48 on 1 df, p=0.01
Wald test = 6.59 on 1 df, p=0.01
Score (logrank) test = 6.59 on 1 df, p=0.01
strata median lower upper
1 risperidone=0 5.366188 5.341547 5.390828
2 risperidone=1 3.935661 3.879535 4.002738
strata median lower upper
1 risperidone=0 6.521561 6.420260 6.603696
2 risperidone=1 4.328542 4.123203 4.520192
Analysis
Competing Risk
> cox_stroke_cs <- coxph(Surv(Stroke_censtime_yrs, Stroke.cr == 1) ~ risperidone, data = dat)
> summary(cox_stroke_cs)
Call:
coxph(formula = Surv(Stroke_censtime_yrs, Stroke.cr == 1) ~ risperidone,
data = dat)
n= 165495, number of events= 1943
coef exp(coef) se(coef) z Pr(>|z|)
risperidone 0.33040 1.39152 0.05493 6.015 1.8e-09 ***
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
risperidone 1.392 0.7186 1.249 1.55
Concordance= 0.526 (se = 0.005 )
Likelihood ratio test= 33.94 on 1 df, p=6e-09
Wald test = 36.18 on 1 df, p=2e-09
Score (logrank) test = 36.51 on 1 df, p=2e-09
>
> # Cause-specific Cox model for death (competing event: stroke)
> cox_death_cs <- coxph(Surv(Stroke_censtime_yrs, Stroke.cr == 2) ~ risperidone, data = dat)
> summary(cox_death_cs)
Call:
coxph(formula = Surv(Stroke_censtime_yrs, Stroke.cr == 2) ~ risperidone,
data = dat)
n= 165495, number of events= 7474
coef exp(coef) se(coef) z Pr(>|z|)
risperidone 0.59437 1.81188 0.02618 22.7 <2e-16 ***
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
risperidone 1.812 0.5519 1.721 1.907
Concordance= 0.549 (se = 0.003 )
Likelihood ratio test= 466.1 on 1 df, p=<2e-16
Wald test = 515.4 on 1 df, p=<2e-16
Score (logrank) test = 530.8 on 1 df, p=<2e-16
> # Cause-specific Cox model for stroke (competing event: death)
> cox_stroke_cs <- coxph(Surv(Stroke_censtime_yrs, Stroke.cr == 1) ~ risperidone, data = dat)
> summary(cox_stroke_cs)
Call:
coxph(formula = Surv(Stroke_censtime_yrs, Stroke.cr == 1) ~ risperidone,
data = dat)
n= 165495, number of events= 5581
coef exp(coef) se(coef) z Pr(>|z|)
risperidone 0.28814 1.33395 0.03472 8.3 <2e-16 ***
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
risperidone 1.334 0.7497 1.246 1.428
Concordance= 0.52 (se = 0.003 )
Likelihood ratio test= 64.77 on 1 df, p=8e-16
Wald test = 68.89 on 1 df, p=<2e-16
Score (logrank) test = 69.37 on 1 df, p=<2e-16
>
> # Cause-specific Cox model for death (competing event: stroke)
> cox_death_cs <- coxph(Surv(Stroke_censtime_yrs, Stroke.cr == 2) ~ risperidone, data = dat)
> summary(cox_death_cs)
Call:
coxph(formula = Surv(Stroke_censtime_yrs, Stroke.cr == 2) ~ risperidone,
data = dat)
n= 165495, number of events= 25807
coef exp(coef) se(coef) z Pr(>|z|)
risperidone 0.63665 1.89014 0.01472 43.26 <2e-16 ***
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
risperidone 1.89 0.5291 1.836 1.945
Concordance= 0.548 (se = 0.001 )
Likelihood ratio test= 1661 on 1 df, p=<2e-16
Wald test = 1871 on 1 df, p=<2e-16
Score (logrank) test = 1935 on 1 df, p=<2e-16
COX model - trained on controls
Causal Survival Forest
summary(treatment_effect_values)
Min. 1st Qu. Median Mean 3rd Qu. Max.
-3.77192 -0.50565 -0.26139 -0.31458 -0.06619 1.90310
Heterogeneous Treatment Effect
Negative Treatment Effect < -0.1 and Positive Treatment Effect > 0.1
Stratified by effect_group
level Negative Positive p test
n 35147 4745
age_diagnosis (mean (SD)) 80.41 (6.64) 81.13 (8.28) <0.001
sex (%) 0 21549 (61.3) 3016 (63.6) 0.003
1 13598 (38.7) 1729 (36.4)
stroke_composite_pre_index_date (%) 0 30305 (86.2) 4160 (87.7) 0.007
1 4842 (13.8) 585 (12.3)
pre_index_date_cvd (%) 0 19830 (56.4) 3216 (67.8) <0.001
1 15317 (43.6) 1529 (32.2)
age_risperidone (mean (SD)) 83.05 (6.68) 83.79 (7.73) <0.001
age_category (%) 65 - 74 6925 (19.7) 1239 (26.1) <0.001
75 - 84 18710 (53.2) 1444 (30.4)
85 - 94 9021 (25.7) 1907 (40.2)
95+ 491 ( 1.4) 155 ( 3.3)
Negative Treatment Effect < 0 and Positive Treatment Effect > 0
Stratified by effect_group
level Negative Positive p test
n 40739 8910
age_diagnosis (mean (SD)) 80.42 (6.70) 80.83 (7.86) <0.001
sex (%) 0 25105 (61.6) 5671 (63.6) <0.001
1 15634 (38.4) 3239 (36.4)
stroke_composite_pre_index_date (%) 0 35245 (86.5) 7837 (88.0) <0.001
1 5494 (13.5) 1073 (12.0)
pre_index_date_cvd (%) 0 23616 (58.0) 6068 (68.1) <0.001
1 17123 (42.0) 2842 (31.9)
age_risperidone (mean (SD)) 83.10 (6.68) 83.61 (7.37) <0.001
age_category (%) 65 - 74 8024 (19.7) 2164 (24.3) <0.001
75 - 84 21410 (52.6) 3263 (36.6)
85 - 94 10722 (26.3) 3246 (36.4)
95+ 583 ( 1.4) 237 ( 2.7)
Causal Forest
summary(treatment_effects)
Min. 1st Qu. Median Mean 3rd Qu. Max.
-0.0400638 0.0004461 0.0038949 0.0045751 0.0079468 0.0481077
Heterogeneous Treatment Effect
Negative Treatment Effect < 0 and Positive Treatment Effect > 0
Stratified by effect_group
level Negative Positive p test
n 10967 38682
age_diagnosis (mean (SD)) 81.40 (7.46) 80.24 (6.74) <0.001
age_risperidone (mean (SD)) 84.00 (6.67) 82.96 (6.84) <0.001
sex (%) 0 6941 (63.3) 23835 (61.6) 0.002
1 4026 (36.7) 14847 (38.4)
stroke_composite_pre_index_date (%) 0 9519 (86.8) 33563 (86.8) 0.947
1 1448 (13.2) 5119 (13.2)
pre_index_date_cvd (%) 0 6941 (63.3) 22743 (58.8) <0.001
1 4026 (36.7) 15939 (41.2)
age_category (%) 65 - 74 2417 (22.0) 7771 (20.1) <0.001
75 - 84 3874 (35.3) 20799 (53.8)
85 - 94 4441 (40.5) 9527 (24.6)
95+ 235 ( 2.1) 585 ( 1.5)
Discontinuation 90 days window
Discontinuation 30 days window
Overall
Call:
coxph(formula = Surv(stime.1, discontinued) ~ sex + age_risperidone +
ethnicity + pre_index_date_stroke + pre_index_date_qof_diabetes +
pre_index_date_haem_cancer + pre_index_date_ihd + pre_index_date_af +
pre_index_date_myocardialinfarction + pre_index_date_heartfailure +
pre_index_date_hypertension, data = dat, weights = weights,
robust = TRUE, cluster = subclass)
n= 28053, number of events= 3194
(411 observations deleted due to missingness)
coef exp(coef) se(coef) robust se z Pr(>|z|)
sex1 0.019024 1.019206 0.037551 0.037526 0.507 0.612191
age_risperidone -0.009074 0.990967 0.002661 0.002670 -3.399 0.000677 ***
ethnicityMixed 0.028725 1.029142 0.293353 0.296991 0.097 0.922949
ethnicityOther 0.034699 1.035308 0.245066 0.243998 0.142 0.886915
ethnicitySouth Asian 0.288754 1.334763 0.163562 0.165862 1.741 0.081696 .
ethnicityUnknown -0.328603 0.719929 0.196723 0.197650 -1.663 0.096402 .
ethnicityWhite -0.194681 0.823097 0.122813 0.124406 -1.565 0.117610
pre_index_date_stroke -0.148224 0.862238 0.058933 0.058922 -2.516 0.011883 *
pre_index_date_qof_diabetes1 -0.161481 0.850883 0.050241 0.050348 -3.207 0.001340 **
pre_index_date_haem_cancer1 -0.124679 0.882780 0.144042 0.144652 -0.862 0.388729
pre_index_date_ihd1 -0.012084 0.987988 0.054100 0.053501 -0.226 0.821300
pre_index_date_af -0.091285 0.912758 0.053758 0.053967 -1.691 0.090744 .
pre_index_date_myocardialinfarction1 -0.060367 0.941419 0.075249 0.074368 -0.812 0.416945
pre_index_date_heartfailure1 -0.029706 0.970731 0.074815 0.074870 -0.397 0.691542
pre_index_date_hypertension1 0.009536 1.009582 0.035801 0.035736 0.267 0.789589
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
sex1 1.0192 0.9812 0.9469 1.0970
age_risperidone 0.9910 1.0091 0.9858 0.9962
ethnicityMixed 1.0291 0.9717 0.5750 1.8419
ethnicityOther 1.0353 0.9659 0.6418 1.6702
ethnicitySouth Asian 1.3348 0.7492 0.9643 1.8475
ethnicityUnknown 0.7199 1.3890 0.4887 1.0605
ethnicityWhite 0.8231 1.2149 0.6450 1.0504
pre_index_date_stroke 0.8622 1.1598 0.7682 0.9678
pre_index_date_qof_diabetes1 0.8509 1.1753 0.7709 0.9391
pre_index_date_haem_cancer1 0.8828 1.1328 0.6649 1.1721
pre_index_date_ihd1 0.9880 1.0122 0.8896 1.0972
pre_index_date_af 0.9128 1.0956 0.8211 1.0146
pre_index_date_myocardialinfarction1 0.9414 1.0622 0.8137 1.0891
pre_index_date_heartfailure1 0.9707 1.0302 0.8382 1.1242
pre_index_date_hypertension1 1.0096 0.9905 0.9413 1.0828
Concordance= 0.538 (se = 0.005 )
Likelihood ratio test= 59.67 on 15 df, p=3e-07
Wald test = 58.89 on 15 df, p=4e-07
Score (logrank) test = 61 on 15 df, p=2e-07, Robust = 56.18 p=1e-06
(Note: the likelihood ratio and score tests assume independence of
observations within a cluster, the Wald and robust score tests do not).
No Stroke
Call:
coxph(formula = Surv(stime.1, discontinued) ~ sex + age_risperidone +
ethnicity + pre_index_date_stroke + pre_index_date_qof_diabetes +
pre_index_date_haem_cancer + pre_index_date_ihd + pre_index_date_af +
pre_index_date_myocardialinfarction + pre_index_date_heartfailure +
pre_index_date_hypertension, data = no_stroke)
n= 24195, number of events= 2812
(389 observations deleted due to missingness)
coef exp(coef) se(coef) z Pr(>|z|)
sex1 0.030991 1.031476 0.040074 0.773 0.439318
age_risperidone -0.009160 0.990881 0.002833 -3.233 0.001224 **
ethnicityMixed -0.023587 0.976689 0.316072 -0.075 0.940511
ethnicityOther -0.001310 0.998691 0.262927 -0.005 0.996026
ethnicitySouth Asian 0.276529 1.318545 0.177134 1.561 0.118494
ethnicityUnknown -0.323348 0.723722 0.203027 -1.593 0.111242
ethnicityWhite -0.227896 0.796207 0.130590 -1.745 0.080963 .
pre_index_date_stroke NA NA 0.000000 NA NA
pre_index_date_qof_diabetes1 -0.207068 0.812964 0.055168 -3.753 0.000174 ***
pre_index_date_haem_cancer1 -0.228094 0.796050 0.159324 -1.432 0.152248
pre_index_date_ihd1 -0.004100 0.995908 0.058415 -0.070 0.944043
pre_index_date_af -0.074517 0.928192 0.059494 -1.253 0.210383
pre_index_date_myocardialinfarction1 -0.053970 0.947460 0.083013 -0.650 0.515603
pre_index_date_heartfailure1 -0.084594 0.918885 0.084378 -1.003 0.316073
pre_index_date_hypertension1 0.004519 1.004529 0.038103 0.119 0.905602
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
sex1 1.0315 0.9695 0.9536 1.1158
age_risperidone 0.9909 1.0092 0.9854 0.9964
ethnicityMixed 0.9767 1.0239 0.5257 1.8147
ethnicityOther 0.9987 1.0013 0.5965 1.6720
ethnicitySouth Asian 1.3185 0.7584 0.9318 1.8658
ethnicityUnknown 0.7237 1.3817 0.4861 1.0774
ethnicityWhite 0.7962 1.2560 0.6164 1.0285
pre_index_date_stroke NA NA NA NA
pre_index_date_qof_diabetes1 0.8130 1.2301 0.7296 0.9058
pre_index_date_haem_cancer1 0.7960 1.2562 0.5825 1.0878
pre_index_date_ihd1 0.9959 1.0041 0.8882 1.1167
pre_index_date_af 0.9282 1.0774 0.8260 1.0430
pre_index_date_myocardialinfarction1 0.9475 1.0555 0.8052 1.1149
pre_index_date_heartfailure1 0.9189 1.0883 0.7788 1.0841
pre_index_date_hypertension1 1.0045 0.9955 0.9322 1.0824
Concordance= 0.536 (se = 0.006 )
Likelihood ratio test= 51.69 on 14 df, p=3e-06
Wald test = 52.65 on 14 df, p=2e-06
Score (logrank) test = 52.9 on 14 df, p=2e-06
With Stroke
Call:
coxph(formula = Surv(stime.1, discontinued) ~ sex + age_risperidone +
ethnicity + pre_index_date_stroke + pre_index_date_qof_diabetes +
pre_index_date_haem_cancer + pre_index_date_ihd + pre_index_date_af +
pre_index_date_myocardialinfarction + pre_index_date_heartfailure +
pre_index_date_hypertension, data = with_stroke)
n= 3858, number of events= 382
(22 observations deleted due to missingness)
coef exp(coef) se(coef) z Pr(>|z|)
sex1 -0.057648 0.943982 0.107858 -0.534 0.593
age_risperidone -0.008081 0.991951 0.007901 -1.023 0.306
ethnicityMixed 0.298613 1.347988 0.792988 0.377 0.706
ethnicityOther 0.324099 1.382784 0.679506 0.477 0.633
ethnicitySouth Asian 0.436795 1.547739 0.439604 0.994 0.320
ethnicityUnknown -1.005812 0.365748 1.062741 -0.946 0.344
ethnicityWhite 0.034425 1.035025 0.361892 0.095 0.924
pre_index_date_stroke -0.188723 0.828016 0.146272 -1.290 0.197
pre_index_date_qof_diabetes1 0.074922 1.077800 0.124470 0.602 0.547
pre_index_date_haem_cancer1 0.503003 1.653679 0.339273 1.483 0.138
pre_index_date_ihd1 -0.063149 0.938804 0.143776 -0.439 0.661
pre_index_date_af -0.175271 0.839230 0.125680 -1.395 0.163
pre_index_date_myocardialinfarction1 -0.081609 0.921632 0.179618 -0.454 0.650
pre_index_date_heartfailure1 0.179570 1.196702 0.163699 1.097 0.273
pre_index_date_hypertension1 0.036947 1.037638 0.104872 0.352 0.725
exp(coef) exp(-coef) lower .95 upper .95
sex1 0.9440 1.0593 0.76411 1.166
age_risperidone 0.9920 1.0081 0.97671 1.007
ethnicityMixed 1.3480 0.7418 0.28490 6.378
ethnicityOther 1.3828 0.7232 0.36505 5.238
ethnicitySouth Asian 1.5477 0.6461 0.65389 3.663
ethnicityUnknown 0.3657 2.7341 0.04556 2.936
ethnicityWhite 1.0350 0.9662 0.50922 2.104
pre_index_date_stroke 0.8280 1.2077 0.62163 1.103
pre_index_date_qof_diabetes1 1.0778 0.9278 0.84448 1.376
pre_index_date_haem_cancer1 1.6537 0.6047 0.85048 3.215
pre_index_date_ihd1 0.9388 1.0652 0.70826 1.244
pre_index_date_af 0.8392 1.1916 0.65600 1.074
pre_index_date_myocardialinfarction1 0.9216 1.0850 0.64814 1.311
pre_index_date_heartfailure1 1.1967 0.8356 0.86825 1.649
pre_index_date_hypertension1 1.0376 0.9637 0.84485 1.274
Concordance= 0.539 (se = 0.015 )
Likelihood ratio test= 12.93 on 15 df, p=0.6
Wald test = 13.02 on 15 df, p=0.6
Score (logrank) test = 13.25 on 15 df, p=0.6
No CVD
Call:
coxph(formula = Surv(stime.1, discontinued) ~ sex + age_risperidone +
ethnicity + pre_index_date_stroke + pre_index_date_qof_diabetes +
pre_index_date_haem_cancer + pre_index_date_ihd + pre_index_date_af +
pre_index_date_myocardialinfarction + pre_index_date_heartfailure +
pre_index_date_hypertension, data = No_CVD)
n= 16669, number of events= 2021
(341 observations deleted due to missingness)
coef exp(coef) se(coef) z Pr(>|z|)
sex1 0.019490 1.019682 0.047579 0.410 0.68207
age_risperidone -0.009715 0.990332 0.003292 -2.951 0.00317 **
ethnicityMixed -0.110132 0.895715 0.410142 -0.269 0.78830
ethnicityOther 0.151112 1.163127 0.310822 0.486 0.62685
ethnicitySouth Asian 0.509543 1.664530 0.213153 2.391 0.01683 *
ethnicityUnknown -0.156704 0.854957 0.238641 -0.657 0.51140
ethnicityWhite -0.042857 0.958048 0.161193 -0.266 0.79033
pre_index_date_stroke NA NA 0.000000 NA NA
pre_index_date_qof_diabetes1 -0.149835 0.860850 0.068721 -2.180 0.02923 *
pre_index_date_haem_cancer1 -0.305251 0.736938 0.201341 -1.516 0.12950
pre_index_date_ihd1 NA NA 0.000000 NA NA
pre_index_date_af -0.135940 0.872895 0.081665 -1.665 0.09599 .
pre_index_date_myocardialinfarction1 NA NA 0.000000 NA NA
pre_index_date_heartfailure1 NA NA 0.000000 NA NA
pre_index_date_hypertension1 0.043759 1.044731 0.044760 0.978 0.32825
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
sex1 1.0197 0.9807 0.9289 1.1193
age_risperidone 0.9903 1.0098 0.9840 0.9967
ethnicityMixed 0.8957 1.1164 0.4009 2.0012
ethnicityOther 1.1631 0.8598 0.6325 2.1389
ethnicitySouth Asian 1.6645 0.6008 1.0961 2.5277
ethnicityUnknown 0.8550 1.1696 0.5356 1.3648
ethnicityWhite 0.9580 1.0438 0.6985 1.3140
pre_index_date_stroke NA NA NA NA
pre_index_date_qof_diabetes1 0.8608 1.1616 0.7524 0.9850
pre_index_date_haem_cancer1 0.7369 1.3570 0.4966 1.0935
pre_index_date_ihd1 NA NA NA NA
pre_index_date_af 0.8729 1.1456 0.7438 1.0244
pre_index_date_myocardialinfarction1 NA NA NA NA
pre_index_date_heartfailure1 NA NA NA NA
pre_index_date_hypertension1 1.0447 0.9572 0.9570 1.1405
Concordance= 0.532 (se = 0.007 )
Likelihood ratio test= 34.77 on 11 df, p=3e-04
Wald test = 36.2 on 11 df, p=2e-04
Score (logrank) test = 36.57 on 11 df, p=1e-04
With CVD
Call:
coxph(formula = Surv(stime.1, discontinued) ~ sex + age_risperidone +
ethnicity + pre_index_date_stroke + pre_index_date_qof_diabetes +
pre_index_date_haem_cancer + pre_index_date_ihd + pre_index_date_af +
pre_index_date_myocardialinfarction + pre_index_date_heartfailure +
pre_index_date_hypertension, data = CVD)
n= 11384, number of events= 1173
(70 observations deleted due to missingness)
coef exp(coef) se(coef) z Pr(>|z|)
sex1 0.023752 1.024037 0.061564 0.386 0.6996
age_risperidone -0.006780 0.993243 0.004618 -1.468 0.1421
ethnicityMixed 0.182474 1.200183 0.421483 0.433 0.6651
ethnicityOther -0.171906 0.842058 0.399844 -0.430 0.6672
ethnicitySouth Asian -0.068042 0.934221 0.254991 -0.267 0.7896
ethnicityUnknown -0.662257 0.515686 0.368095 -1.799 0.0720 .
ethnicityWhite -0.458243 0.632394 0.189885 -2.413 0.0158 *
pre_index_date_stroke -0.118844 0.887946 0.068785 -1.728 0.0840 .
pre_index_date_qof_diabetes1 -0.170967 0.842849 0.073871 -2.314 0.0206 *
pre_index_date_haem_cancer1 0.106377 1.112242 0.206500 0.515 0.6065
pre_index_date_ihd1 0.017707 1.017864 0.063585 0.278 0.7807
pre_index_date_af -0.052137 0.949198 0.072076 -0.723 0.4695
pre_index_date_myocardialinfarction1 -0.046902 0.954181 0.076790 -0.611 0.5413
pre_index_date_heartfailure1 -0.024305 0.975988 0.079780 -0.305 0.7606
pre_index_date_hypertension1 -0.056020 0.945520 0.060037 -0.933 0.3508
---
Signif. codes: 0 ‘***’ 0.001 ‘**’ 0.01 ‘*’ 0.05 ‘.’ 0.1 ‘ ’ 1
exp(coef) exp(-coef) lower .95 upper .95
sex1 1.0240 0.9765 0.9076 1.1554
age_risperidone 0.9932 1.0068 0.9843 1.0023
ethnicityMixed 1.2002 0.8332 0.5254 2.7417
ethnicityOther 0.8421 1.1876 0.3846 1.8437
ethnicitySouth Asian 0.9342 1.0704 0.5668 1.5399
ethnicityUnknown 0.5157 1.9392 0.2506 1.0610
ethnicityWhite 0.6324 1.5813 0.4359 0.9175
pre_index_date_stroke 0.8879 1.1262 0.7760 1.0161
pre_index_date_qof_diabetes1 0.8428 1.1865 0.7292 0.9742
pre_index_date_haem_cancer1 1.1122 0.8991 0.7420 1.6671
pre_index_date_ihd1 1.0179 0.9824 0.8986 1.1530
pre_index_date_af 0.9492 1.0535 0.8241 1.0932
pre_index_date_myocardialinfarction1 0.9542 1.0480 0.8209 1.1092
pre_index_date_heartfailure1 0.9760 1.0246 0.8347 1.1412
pre_index_date_hypertension1 0.9455 1.0576 0.8406 1.0636
Concordance= 0.545 (se = 0.009 )
Likelihood ratio test= 23.97 on 15 df, p=0.07
Wald test = 25.2 on 15 df, p=0.05
Score (logrank) test = 25.4 on 15 df, p=0.04
Discontinuation baseline characteristics *Overall
Stratified by discontinued
Overall 0 1 p test
n 28464 25217 3242
sex = 1 (%) 10847 ( 38.1) 9645 ( 38.2) 1202 ( 37.1) 0.203
Prescribed_other_antipsychotic_Prior = 1 (%) 7377 ( 25.9) 6592 ( 26.1) 785 ( 24.2) 0.019
ethnicity (%) <0.001
Black 487 ( 1.7) 418 ( 1.7) 69 ( 2.1)
Mixed 98 ( 0.3) 84 ( 0.3) 14 ( 0.4)
Other 151 ( 0.5) 129 ( 0.5) 22 ( 0.7)
South Asian 475 ( 1.7) 391 ( 1.6) 84 ( 2.6)
Unknown 454 ( 1.6) 411 ( 1.6) 43 ( 1.3)
White 26799 ( 94.2) 23784 ( 94.3) 3010 ( 92.8)
death_composite = 1 (%) 22331 ( 78.5) 19823 ( 78.6) 2505 ( 77.3) 0.084
pre_index_date_angina = 1 (%) 3344 ( 11.7) 2983 ( 11.8) 361 ( 11.1) 0.260
pre_index_date_heartfailure = 1 (%) 2199 ( 7.7) 1989 ( 7.9) 210 ( 6.5) 0.005
pre_index_date_myocardialinfarction = 1 (%) 2316 ( 8.1) 2086 ( 8.3) 230 ( 7.1) 0.023
pre_index_date_tia = 1 (%) 2641 ( 9.3) 2354 ( 9.3) 286 ( 8.8) 0.360
pre_index_date_falls = 1 (%) 11748 ( 41.3) 10555 ( 41.9) 1192 ( 36.8) <0.001
pre_index_date_lowerlimbfracture = 1 (%) 4536 ( 15.9) 4050 ( 16.1) 486 ( 15.0) 0.123
pre_index_date_ihd = 1 (%) 4717 ( 16.6) 4224 ( 16.8) 493 ( 15.2) 0.028
pre_index_date_pad = 1 (%) 2207 ( 7.8) 1983 ( 7.9) 224 ( 6.9) 0.060
pre_index_date_revasc = 1 (%) 1514 ( 5.3) 1362 ( 5.4) 152 ( 4.7) 0.097
pre_index_date_qof_diabetes = 1 (%) 4979 ( 17.5) 4483 ( 17.8) 496 ( 15.3) 0.001
pre_index_date_fh_diabetes = 1 (%) 5824 ( 20.5) 5116 ( 20.3) 708 ( 21.8) 0.042
pre_index_date_fh_premature_cvd = 1 (%) 2233 ( 7.8) 1997 ( 7.9) 236 ( 7.3) 0.215
pre_index_date_pulmonary_embolism = 1 (%) 728 ( 2.6) 656 ( 2.6) 72 ( 2.2) 0.218
pre_index_date_deep_vein_thrombosis = 1 (%) 1468 ( 5.2) 1322 ( 5.2) 146 ( 4.5) 0.080
pre_index_date_haem_cancer = 1 (%) 540 ( 1.9) 489 ( 1.9) 51 ( 1.6) 0.171
pre_index_date_solid_cancer = 1 (%) 4517 ( 15.9) 4037 ( 16.0) 480 ( 14.8) 0.082
pre_index_date_hearing_loss = 1 (%) 7645 ( 26.9) 6788 ( 26.9) 857 ( 26.4) 0.573
primary_death_stroke = 1 (%) 730 (100.0) 666 (100.0) 64 (100.0) NA
stroke_composite_pre_index_date = 1 (%) 3880 ( 13.6) 3494 ( 13.9) 386 ( 11.9) 0.003
pre_index_date_VTE = 1 (%) 2020 ( 7.1) 1817 ( 7.2) 203 ( 6.3) 0.053
pre_index_date_cvd = 1 (%) 11454 ( 40.2) 10273 ( 40.7) 1180 ( 36.4) <0.001
BMI (%) 0.212
Missing 5505 ( 19.3) 4893 ( 19.4) 612 ( 18.9)
Normal 11024 ( 38.7) 9721 ( 38.5) 1299 ( 40.1)
Obesity 2973 ( 10.4) 2653 ( 10.5) 320 ( 9.9)
Overweight 7175 ( 25.2) 6348 ( 25.2) 826 ( 25.5)
Severely Obese 189 ( 0.7) 175 ( 0.7) 14 ( 0.4)
Underweight 1598 ( 5.6) 1427 ( 5.7) 171 ( 5.3)
pre_index_date_hypertension = 1 (%) 13620 ( 48.5) 12206 ( 49.1) 1413 ( 44.2) <0.001
No stroke
Stratified by discontinued
Overall 0 1 p test
n 24584 21723 2856
sex = 1 (%) 9100 ( 37.0) 8064 ( 37.1) 1036 ( 36.3) 0.389
Prescribed_other_antipsychotic_Prior = 1 (%) 6253 ( 25.4) 5580 ( 25.7) 673 ( 23.6) 0.015
ethnicity (%) <0.001
Black 416 ( 1.7) 355 ( 1.6) 61 ( 2.1)
Mixed 86 ( 0.3) 74 ( 0.3) 12 ( 0.4)
Other 129 ( 0.5) 110 ( 0.5) 19 ( 0.7)
South Asian 372 ( 1.5) 303 ( 1.4) 69 ( 2.4)
Unknown 425 ( 1.7) 383 ( 1.8) 42 ( 1.5)
White 23156 ( 94.2) 20498 ( 94.4) 2653 ( 92.9)
death_composite = 1 (%) 19174 ( 78.0) 16975 ( 78.1) 2196 ( 76.9) 0.135
pre_index_date_angina = 1 (%) 2741 ( 11.1) 2433 ( 11.2) 308 ( 10.8) 0.527
pre_index_date_heartfailure = 1 (%) 1748 ( 7.1) 1585 ( 7.3) 163 ( 5.7) 0.002
pre_index_date_myocardialinfarction = 1 (%) 1826 ( 7.4) 1640 ( 7.5) 186 ( 6.5) 0.051
pre_index_date_tia = 1 (%) 1749 ( 7.1) 1548 ( 7.1) 200 ( 7.0) 0.840
pre_index_date_falls = 1 (%) 9769 ( 39.7) 8745 ( 40.3) 1023 ( 35.8) <0.001
pre_index_date_lowerlimbfracture = 1 (%) 3838 ( 15.6) 3418 ( 15.7) 420 ( 14.7) 0.163
pre_index_date_ihd = 1 (%) 3847 ( 15.6) 3433 ( 15.8) 414 ( 14.5) 0.075
pre_index_date_pad = 1 (%) 1770 ( 7.2) 1582 ( 7.3) 188 ( 6.6) 0.186
pre_index_date_revasc = 1 (%) 1200 ( 4.9) 1075 ( 4.9) 125 ( 4.4) 0.198
pre_index_date_qof_diabetes = 1 (%) 4090 ( 16.6) 3686 ( 17.0) 404 ( 14.1) <0.001
pre_index_date_fh_diabetes = 1 (%) 5021 ( 20.4) 4381 ( 20.2) 640 ( 22.4) 0.006
pre_index_date_fh_premature_cvd = 1 (%) 1936 ( 7.9) 1726 ( 7.9) 210 ( 7.4) 0.285
pre_index_date_pulmonary_embolism = 1 (%) 601 ( 2.4) 539 ( 2.5) 62 ( 2.2) 0.345
pre_index_date_deep_vein_thrombosis = 1 (%) 1205 ( 4.9) 1085 ( 5.0) 120 ( 4.2) 0.072
pre_index_date_haem_cancer = 1 (%) 473 ( 1.9) 431 ( 2.0) 42 ( 1.5) 0.071
pre_index_date_solid_cancer = 1 (%) 3872 ( 15.8) 3441 ( 15.8) 431 ( 15.1) 0.314
pre_index_date_hearing_loss = 1 (%) 6490 ( 26.4) 5748 ( 26.5) 742 ( 26.0) 0.600
primary_death_stroke = 1 (%) 523 (100.0) 475 (100.0) 48 (100.0) NA
stroke_composite_pre_index_date = 1 (%) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) NaN
pre_index_date_VTE = 1 (%) 1663 ( 6.8) 1494 ( 6.9) 169 ( 5.9) 0.060
pre_index_date_cvd = 1 (%) 7774 ( 31.6) 6955 ( 32.0) 818 ( 28.6) <0.001
BMI (%) 0.204
Missing 4871 ( 19.8) 4329 ( 19.9) 542 ( 19.0)
Normal 9536 ( 38.8) 8385 ( 38.6) 1147 ( 40.2)
Obesity 2495 ( 10.1) 2218 ( 10.2) 277 ( 9.7)
Overweight 6128 ( 24.9) 5401 ( 24.9) 726 ( 25.4)
Severely Obese 152 ( 0.6) 141 ( 0.6) 11 ( 0.4)
Underweight 1402 ( 5.7) 1249 ( 5.7) 153 ( 5.4)
pre_index_date_hypertension = 1 (%) 11896 ( 49.2) 10635 ( 49.7) 1260 ( 44.8) <0.001
with stroke
Stratified by discontinued
Overall 0 1 p test
n 3880 3494 386
sex = 1 (%) 1747 ( 45.0) 1581 ( 45.2) 166 ( 43.0) 0.431
Prescribed_other_antipsychotic_Prior = 1 (%) 1124 ( 29.0) 1012 ( 29.0) 112 ( 29.0) 1.000
ethnicity (%) 0.418
Black 71 ( 1.8) 63 ( 1.8) 8 ( 2.1)
Mixed 12 ( 0.3) 10 ( 0.3) 2 ( 0.5)
Other 22 ( 0.6) 19 ( 0.5) 3 ( 0.8)
South Asian 103 ( 2.7) 88 ( 2.5) 15 ( 3.9)
Unknown 29 ( 0.7) 28 ( 0.8) 1 ( 0.3)
White 3643 ( 93.9) 3286 ( 94.0) 357 ( 92.5)
death_composite = 1 (%) 3157 ( 81.4) 2848 ( 81.5) 309 ( 80.1) 0.529
pre_index_date_angina = 1 (%) 603 ( 15.5) 550 ( 15.7) 53 ( 13.7) 0.337
pre_index_date_heartfailure = 1 (%) 451 ( 11.6) 404 ( 11.6) 47 ( 12.2) 0.785
pre_index_date_myocardialinfarction = 1 (%) 490 ( 12.6) 446 ( 12.8) 44 ( 11.4) 0.493
pre_index_date_tia = 1 (%) 892 ( 23.0) 806 ( 23.1) 86 ( 22.3) 0.775
pre_index_date_falls = 1 (%) 1979 ( 51.0) 1810 ( 51.8) 169 ( 43.8) 0.003
pre_index_date_lowerlimbfracture = 1 (%) 698 ( 18.0) 632 ( 18.1) 66 ( 17.1) 0.681
pre_index_date_ihd = 1 (%) 870 ( 22.4) 791 ( 22.6) 79 ( 20.5) 0.364
pre_index_date_pad = 1 (%) 437 ( 11.3) 401 ( 11.5) 36 ( 9.3) 0.237
pre_index_date_revasc = 1 (%) 314 ( 8.1) 287 ( 8.2) 27 ( 7.0) 0.462
pre_index_date_qof_diabetes = 1 (%) 889 ( 22.9) 797 ( 22.8) 92 ( 23.8) 0.696
pre_index_date_fh_diabetes = 1 (%) 803 ( 20.7) 735 ( 21.0) 68 ( 17.6) 0.132
pre_index_date_fh_premature_cvd = 1 (%) 297 ( 7.7) 271 ( 7.8) 26 ( 6.7) 0.539
pre_index_date_pulmonary_embolism = 1 (%) 127 ( 3.3) 117 ( 3.3) 10 ( 2.6) 0.520
pre_index_date_deep_vein_thrombosis = 1 (%) 263 ( 6.8) 237 ( 6.8) 26 ( 6.7) 1.000
pre_index_date_haem_cancer = 1 (%) 67 ( 1.7) 58 ( 1.7) 9 ( 2.3) 0.450
pre_index_date_solid_cancer = 1 (%) 645 ( 16.6) 596 ( 17.1) 49 ( 12.7) 0.035
pre_index_date_hearing_loss = 1 (%) 1155 ( 29.8) 1040 ( 29.8) 115 ( 29.8) 1.000
primary_death_stroke = 1 (%) 207 (100.0) 191 (100.0) 16 (100.0) NA
stroke_composite_pre_index_date = 1 (%) 3880 (100.0) 3494 (100.0) 386 (100.0) NaN
pre_index_date_VTE = 1 (%) 357 ( 9.2) 323 ( 9.2) 34 ( 8.8) 0.850
pre_index_date_cvd = 1 (%) 3680 ( 94.8) 3318 ( 95.0) 362 ( 93.8) 0.382
BMI (%) 0.863
Missing 634 ( 16.3) 564 ( 16.1) 70 ( 18.1)
Normal 1488 ( 38.4) 1336 ( 38.2) 152 ( 39.4)
Obesity 478 ( 12.3) 435 ( 12.4) 43 ( 11.1)
Overweight 1047 ( 27.0) 947 ( 27.1) 100 ( 25.9)
Severely Obese 37 ( 1.0) 34 ( 1.0) 3 ( 0.8)
Underweight 196 ( 5.1) 178 ( 5.1) 18 ( 4.7)
pre_index_date_hypertension = 1 (%) 1724 ( 44.7) 1571 ( 45.2) 153 ( 40.1) 0.062
No CVD
Stratified by discontinued
Overall 0 1 p test
n 17010 14944 2062
sex = 1 (%) 5823 ( 34.2) 5130 ( 34.3) 693 ( 33.6) 0.535
Prescribed_other_antipsychotic_Prior = 1 (%) 4060 ( 23.9) 3604 ( 24.1) 456 ( 22.1) 0.049
ethnicity (%) 0.001
Black 314 ( 1.8) 274 ( 1.8) 40 ( 1.9)
Mixed 60 ( 0.4) 53 ( 0.4) 7 ( 0.3)
Other 94 ( 0.6) 80 ( 0.5) 14 ( 0.7)
South Asian 238 ( 1.4) 187 ( 1.3) 51 ( 2.5)
Unknown 327 ( 1.9) 294 ( 2.0) 33 ( 1.6)
White 15977 ( 93.9) 14056 ( 94.1) 1917 ( 93.0)
death_composite = 1 (%) 12988 ( 76.4) 11426 ( 76.5) 1560 ( 75.7) 0.437
pre_index_date_angina = 1 (%) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) NaN
pre_index_date_heartfailure = 1 (%) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) NaN
pre_index_date_myocardialinfarction = 1 (%) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) NaN
pre_index_date_tia = 1 (%) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) NaN
pre_index_date_falls = 1 (%) 6200 ( 36.4) 5535 ( 37.0) 664 ( 32.2) <0.001
pre_index_date_lowerlimbfracture = 1 (%) 2527 ( 14.9) 2233 ( 14.9) 294 ( 14.3) 0.432
pre_index_date_ihd = 1 (%) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) NaN
pre_index_date_pad = 1 (%) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) NaN
pre_index_date_revasc = 1 (%) 40 ( 0.2) 36 ( 0.2) 4 ( 0.2) 0.865
pre_index_date_qof_diabetes = 1 (%) 2361 ( 13.9) 2108 ( 14.1) 253 ( 12.3) 0.026
pre_index_date_fh_diabetes = 1 (%) 3393 ( 19.9) 2955 ( 19.8) 438 ( 21.2) 0.125
pre_index_date_fh_premature_cvd = 1 (%) 1124 ( 6.6) 1002 ( 6.7) 122 ( 5.9) 0.192
pre_index_date_pulmonary_embolism = 1 (%) 335 ( 2.0) 299 ( 2.0) 36 ( 1.7) 0.486
pre_index_date_deep_vein_thrombosis = 1 (%) 753 ( 4.4) 675 ( 4.5) 78 ( 3.8) 0.144
pre_index_date_haem_cancer = 1 (%) 292 ( 1.7) 266 ( 1.8) 26 ( 1.3) 0.107
pre_index_date_solid_cancer = 1 (%) 2599 ( 15.3) 2301 ( 15.4) 298 ( 14.5) 0.278
pre_index_date_hearing_loss = 1 (%) 4102 ( 24.1) 3582 ( 24.0) 520 ( 25.2) 0.224
primary_death_stroke = 1 (%) 339 (100.0) 310 (100.0) 29 (100.0) NA
stroke_composite_pre_index_date = 1 (%) 200 ( 1.2) 176 ( 1.2) 24 ( 1.2) 1.000
pre_index_date_VTE = 1 (%) 1010 ( 5.9) 902 ( 6.0) 108 ( 5.2) 0.165
pre_index_date_cvd = 1 (%) 0 ( 0.0) 0 ( 0.0) 0 ( 0.0) NaN
BMI (%) 0.280
Missing 3702 ( 21.8) 3269 ( 21.9) 433 ( 21.0)
Normal 6625 ( 38.9) 5779 ( 38.7) 842 ( 40.8)
Obesity 1545 ( 9.1) 1373 ( 9.2) 172 ( 8.3)
Overweight 4063 ( 23.9) 3565 ( 23.9) 498 ( 24.2)
Severely Obese 91 ( 0.5) 83 ( 0.6) 8 ( 0.4)
Underweight 984 ( 5.8) 875 ( 5.9) 109 ( 5.3)
pre_index_date_hypertension = 1 (%) 8420 ( 50.5) 7466 ( 51.0) 953 ( 47.2) 0.001
CVD
Stratified by discontinued
Overall 0 1 p test
n 11454 10273 1180
sex = 1 (%) 5024 ( 43.9) 4515 ( 44.0) 509 ( 43.1) 0.615
Prescribed_other_antipsychotic_Prior = 1 (%) 3317 ( 29.0) 2988 ( 29.1) 329 ( 27.9) 0.406
ethnicity (%) 0.007
Black 173 ( 1.5) 144 ( 1.4) 29 ( 2.5)
Mixed 38 ( 0.3) 31 ( 0.3) 7 ( 0.6)
Other 57 ( 0.5) 49 ( 0.5) 8 ( 0.7)
South Asian 237 ( 2.1) 204 ( 2.0) 33 ( 2.8)
Unknown 127 ( 1.1) 117 ( 1.1) 10 ( 0.8)
White 10822 ( 94.5) 9728 ( 94.7) 1093 ( 92.6)
death_composite = 1 (%) 9343 ( 81.6) 8397 ( 81.7) 945 ( 80.1) 0.178
pre_index_date_angina = 1 (%) 3344 ( 29.2) 2983 ( 29.0) 361 ( 30.6) 0.280
pre_index_date_heartfailure = 1 (%) 2199 ( 19.2) 1989 ( 19.4) 210 ( 17.8) 0.210
pre_index_date_myocardialinfarction = 1 (%) 2316 ( 20.2) 2086 ( 20.3) 230 ( 19.5) 0.534
pre_index_date_tia = 1 (%) 2641 ( 23.1) 2354 ( 22.9) 286 ( 24.2) 0.324
pre_index_date_falls = 1 (%) 5548 ( 48.4) 5020 ( 48.9) 528 ( 44.7) 0.008
pre_index_date_lowerlimbfracture = 1 (%) 2009 ( 17.5) 1817 ( 17.7) 192 ( 16.3) 0.242
pre_index_date_ihd = 1 (%) 4717 ( 41.2) 4224 ( 41.1) 493 ( 41.8) 0.684
pre_index_date_pad = 1 (%) 2207 ( 19.3) 1983 ( 19.3) 224 ( 19.0) 0.822
pre_index_date_revasc = 1 (%) 1474 ( 12.9) 1326 ( 12.9) 148 ( 12.5) 0.757
pre_index_date_qof_diabetes = 1 (%) 2618 ( 22.9) 2375 ( 23.1) 243 ( 20.6) 0.055
pre_index_date_fh_diabetes = 1 (%) 2431 ( 21.2) 2161 ( 21.0) 270 ( 22.9) 0.152
pre_index_date_fh_premature_cvd = 1 (%) 1109 ( 9.7) 995 ( 9.7) 114 ( 9.7) 1.000
pre_index_date_pulmonary_embolism = 1 (%) 393 ( 3.4) 357 ( 3.5) 36 ( 3.1) 0.500
pre_index_date_deep_vein_thrombosis = 1 (%) 715 ( 6.2) 647 ( 6.3) 68 ( 5.8) 0.512
pre_index_date_haem_cancer = 1 (%) 248 ( 2.2) 223 ( 2.2) 25 ( 2.1) 0.991
pre_index_date_solid_cancer = 1 (%) 1918 ( 16.7) 1736 ( 16.9) 182 ( 15.4) 0.214
pre_index_date_hearing_loss = 1 (%) 3543 ( 30.9) 3206 ( 31.2) 337 ( 28.6) 0.067
primary_death_stroke = 1 (%) 391 (100.0) 356 (100.0) 35 (100.0) NA
stroke_composite_pre_index_date = 1 (%) 3680 ( 32.1) 3318 ( 32.3) 362 ( 30.7) 0.273
pre_index_date_VTE = 1 (%) 1010 ( 8.8) 915 ( 8.9) 95 ( 8.1) 0.353
pre_index_date_cvd = 1 (%) 11454 (100.0) 10273 (100.0) 1180 (100.0) NaN
BMI (%) 0.793
Missing 1803 ( 15.7) 1624 ( 15.8) 179 ( 15.2)
Normal 4399 ( 38.4) 3942 ( 38.4) 457 ( 38.7)
Obesity 1428 ( 12.5) 1280 ( 12.5) 148 ( 12.5)
Overweight 3112 ( 27.2) 2783 ( 27.1) 328 ( 27.8)
Severely Obese 98 ( 0.9) 92 ( 0.9) 6 ( 0.5)
Underweight 614 ( 5.4) 552 ( 5.4) 62 ( 5.3)
pre_index_date_hypertension = 1 (%) 5200 ( 45.7) 4740 ( 46.4) 460 ( 39.2) <0.001
Random Forest - python
Accuracy: 0.578
Precision: 0.585
Recall: 0.515
F1 Score: 0.548
ROC AUC Score: 0.578
outcome subgroup event_count person_time incidence_rate number_of_patients NNH ci.l_NNH ci.u_NNH Adjusted_HR Unadjusted_HR
102 stroke.hes with_stroke 1379 16443. 83.9 21866 81.0 45.3 386. 1.18 (1.02, 1.36) 1.18 (1.03, 1.36)
One year follow-up results
outcome subgroup Group N.events Person.years.at.risk Incidence_rate_per_1000_PY Adjusted_HR NNH Lower_CI_NNH Upper_CI_NNH ARR
1 Stroke CVD history Matched Controls 3278 44309. 74.0 1.23 (1.13, 1.33) 65.8 48.4 103. 0.0152
2 Stroke CVD history Risperidone Users 748 7902. 94.7 1.23 (1.13, 1.33) 65.8 48.4 103. 0.0152
3 Stroke HES stroke Matched Controls 4479 112584. 39.8 1.31 (1.22, 1.40) 88.0 71.0 116. 0.0114
4 Stroke HES stroke Risperidone Users 1085 20311. 53.4 1.31 (1.22, 1.40) 88.0 71.0 116. 0.0114
5 Stroke No CVD history Matched Controls 1201 68275. 17.6 1.54 (1.36, 1.74) 111. 86.1 155. 0.009
6 Stroke No CVD history Risperidone Users 337 12408. 27.2 1.54 (1.36, 1.74) 111. 86.1 155. 0.009
7 Stroke Pre-Covid period (Overall) Matched Controls 4302 103818. 41.4 1.27 (1.19, 1.36) 94.4 74.4 129. 0.0106
8 Stroke Pre-Covid period (Overall) Risperidone Users 1038 19121. 54.3 1.27 (1.19, 1.36) 94.4 74.4 129. 0.0106
9 Stroke Pre-Covid period (No CVD history) Matched Controls 1154 63142. 18.3 1.51 (1.33, 1.71) 112. 86.0 161. 0.0089
10 Stroke Pre-Covid period (No CVD history) Risperidone Users 324 11712. 27.7 1.51 (1.33, 1.71) 112. 86.0 161. 0.0089
11 Stroke Pre-Covid period (No stroke history) Matched Controls 1942 91184. 21.3 1.39 (1.26, 1.54) 131. 100. 188. 0.0076
12 Stroke Pre-Covid period (No stroke history) Risperidone Users 498 16758. 29.7 1.39 (1.26, 1.54) 131. 100. 188. 0.0076
13 Stroke Pre-Covid period (CVD history) Matched Controls 3148 40676. 77.4 1.19 (1.10, 1.29) 74.4 52.1 130. 0.0134
14 Stroke Pre-Covid period (CVD history) Risperidone Users 714 7410. 96.4 1.19 (1.10, 1.29) 74.4 52.1 130. 0.0134
15 Stroke Pre-Covid period (Stroke history) Matched Controls 2360 12634. 187. 1.19 (1.08, 1.30) 38.5 25.0 83.6 0.0259
16 Stroke Pre-Covid period (Stroke history) Risperidone Users 540 2363. 228. 1.19 (1.08, 1.30) 38.5 25.0 83.6 0.0259
17 Stroke all Matched Controls 4479 112584. 39.8 1.31 (1.22, 1.40) 88.0 71.0 116. 0.0114
18 Stroke all Risperidone Users 1085 20311. 53.4 1.31 (1.22, 1.40) 88.0 71.0 116. 0.0114
19 Stroke Stroke type - haemorrhagic Matched Controls 28 198. 141. 2.55 (1.56, 4.18) 6.89 4.61 13.6 0.145
20 Stroke Stroke type - haemorrhagic Risperidone Users 46 136. 339. 2.55 (1.56, 4.18) 6.89 4.61 13.6 0.145
21 Stroke Stroke type - ischaemic Matched Controls 1848 8615. 214. 1.23 (1.12, 1.35) 17.2 13.4 24.0 0.0581
22 Stroke Stroke type - ischaemic Risperidone Users 622 2069. 301. 1.23 (1.12, 1.35) 17.2 13.4 24.0 0.0581
23 Stroke No stroke history Matched Controls 2025 98709. 20.5 1.42 (1.29, 1.57) 125. 97.8 173. 0.008
24 Stroke No stroke history Risperidone Users 521 17775. 29.3 1.42 (1.29, 1.57) 125. 97.8 173. 0.008
25 Stroke Prescription age 65 - 74 years Matched Controls 439 13395. 32.8 1.41 (1.15, 1.72) 66.6 44.0 137. 0.015
26 Stroke Prescription age 65 - 74 years Risperidone Users 125 2538. 49.2 1.41 (1.15, 1.72) 66.6 44.0 137. 0.015
27 Stroke Prescription age 75 - 84 years Matched Controls 1974 52198. 37.8 1.30 (1.17, 1.44) 94.0 68.6 149. 0.0106
28 Stroke Prescription age 75 - 84 years Risperidone Users 479 9425. 50.8 1.30 (1.17, 1.44) 94.0 68.6 149. 0.0106
29 Stroke risperidone_Age_85+ Matched Controls 2066 46991. 44.0 1.29 (1.17, 1.43) 88.9 64.5 143. 0.0112
30 Stroke risperidone_Age_85+ Risperidone Users 481 8348. 57.6 1.29 (1.17, 1.43) 88.9 64.5 143. 0.0112
31 Stroke Stroke recency 1 - 5 years Matched Controls 384 2227. 172. 1.23 (1.03, 1.47) 30.7 17.5 123. 0.0326
32 Stroke Stroke recency 1 - 5 years Risperidone Users 192 885. 217. 1.23 (1.03, 1.47) 30.7 17.5 123. 0.0326
33 Stroke Stroke recency less than 1 year Matched Controls 172 354. 485. 1.03 (0.80, 1.32) 144. 14.8 Inf 0.0069
34 Stroke Stroke recency less than 1 year Risperidone Users 123 228. 539. 1.03 (0.80, 1.32) 144. 14.8 Inf 0.0069
35 Stroke Stroke recency over 5 years Matched Controls 297 2713. 109. 1.16 (0.94, 1.44) 76.8 31.2 Inf 0.013
36 Stroke Stroke recency over 5 years Risperidone Users 127 993. 128. 1.16 (0.94, 1.44) 76.8 31.2 Inf 0.013
37 Stroke Stroke history Matched Controls 2454 13875. 177. 1.22 (1.11, 1.34) 33.9 23.4 61.5 0.0295
38 Stroke Stroke history Risperidone Users 564 2535. 222. 1.22 (1.11, 1.34) 33.9 23.4 61.5 0.0295
12 weeks follow-up results
outcome subgroup Group N.events Person.years.at.risk Incidence_rate_per_1000_PY Adjusted_HR NNH Lower_CI_NNH Upper_CI_NNH ARR
1 Stroke CVD history Matched Controls 1220 12945. 94.2 1.36 (1.20, 1.54) 2707. 1044. Inf 0.0004
2 Stroke CVD history Risperidone Users 345 2700. 128. 1.36 (1.20, 1.54) 2707. 1044. Inf 0.0004
3 Stroke HES stroke Matched Controls 1560 31714. 49.2 1.45 (1.30, 1.61) 6534. 2533. Inf 0.0002
4 Stroke HES stroke Risperidone Users 462 6577. 70.2 1.45 (1.30, 1.61) 6534. 2533. Inf 0.0002
5 Stroke No CVD history Matched Controls 340 18769. 18.1 1.81 (1.46, 2.23) Inf Inf Inf 0
6 Stroke No CVD history Risperidone Users 117 3878. 30.2 1.81 (1.46, 2.23) Inf Inf Inf 0
7 Stroke Pre-Covid period (Overall) Matched Controls 1484 28832. 51.5 1.43 (1.28, 1.59) 8106. 2670. Inf 0.0001
8 Stroke Pre-Covid period (Overall) Risperidone Users 442 6080. 72.7 1.43 (1.28, 1.59) 8106. 2670. Inf 0.0001
9 Stroke Pre-Covid period (No CVD history) Matched Controls 325 17122. 19.0 1.73 (1.39, 2.15) Inf Inf Inf 0
10 Stroke Pre-Covid period (No CVD history) Risperidone Users 109 3599. 30.3 1.73 (1.39, 2.15) Inf Inf Inf 0
11 Stroke Pre-Covid period (No stroke history) Matched Controls 536 24982. 21.5 1.75 (1.48, 2.07) 61616. 9274. Inf 0
12 Stroke Pre-Covid period (No stroke history) Risperidone Users 183 5253. 34.8 1.75 (1.48, 2.07) 61616. 9274. Inf 0
13 Stroke Pre-Covid period (CVD history) Matched Controls 1159 11710. 99.0 1.35 (1.20, 1.53) 3344. 1094. Inf 0.0003
14 Stroke Pre-Covid period (CVD history) Risperidone Users 333 2482. 134. 1.35 (1.20, 1.53) 3344. 1094. Inf 0.0003
15 Stroke Pre-Covid period (Stroke history) Matched Controls 948 3850. 246. 1.27 (1.10, 1.46) 1300. 397. Inf 0.0008
16 Stroke Pre-Covid period (Stroke history) Risperidone Users 259 828. 313. 1.27 (1.10, 1.46) 1300. 397. Inf 0.0008
17 Stroke all Matched Controls 1560 31714. 49.2 1.45 (1.30, 1.61) 6534. 2533. Inf 0.0002
18 Stroke all Risperidone Users 462 6577. 70.2 1.45 (1.30, 1.61) 6534. 2533. Inf 0.0002
19 Stroke Stroke type - ischaemic Matched Controls 748 2667. 280. 1.27 (1.10, 1.46) 1335. 381. Inf 0.0007
20 Stroke Stroke type - ischaemic Risperidone Users 290 744. 390. 1.27 (1.10, 1.46) 1335. 381. Inf 0.0007
21 Stroke No stroke history Matched Controls 567 27431. 20.7 1.79 (1.52, 2.11) 64663. 9986. Inf 0
22 Stroke No stroke history Risperidone Users 194 5670. 34.2 1.79 (1.52, 2.11) 64663. 9986. Inf 0
23 Stroke Prescription age 65 - 74 years Matched Controls 158 3549. 44.5 1.26 (0.91, 1.76) 4206. 1184. Inf 0.0002
24 Stroke Prescription age 65 - 74 years Risperidone Users 49 762. 64.3 1.26 (0.91, 1.76) 4206. 1184. Inf 0.0002
25 Stroke Prescription age 75 - 84 years Matched Controls 695 14311. 48.6 1.50 (1.28, 1.76) 24941. 3068. Inf 0
26 Stroke Prescription age 75 - 84 years Risperidone Users 215 2964. 72.5 1.50 (1.28, 1.76) 24941. 3068. Inf 0
27 Stroke risperidone_Age_85+ Matched Controls 707 13855. 51.0 1.45 (1.24, 1.69) 4002. 1444. Inf 0.0002
28 Stroke risperidone_Age_85+ Risperidone Users 198 2851. 69.4 1.45 (1.24, 1.69) 4002. 1444. Inf 0.0002
29 Stroke Stroke recency 1 - 5 years Matched Controls 145 683. 212. 1.11 (0.83, 1.49) 527. 222. Inf 0.0019
30 Stroke Stroke recency 1 - 5 years Risperidone Users 75 309. 243. 1.11 (0.83, 1.49) 527. 222. Inf 0.0019
31 Stroke Stroke recency less than 1 year Matched Controls 89 129. 691. 1.08 (0.78, 1.50) 842. 106. Inf 0.0012
32 Stroke Stroke recency less than 1 year Risperidone Users 76 96.6 787. 1.08 (0.78, 1.50) 842. 106. Inf 0.0012
33 Stroke Stroke recency over 5 years Matched Controls 99 816. 121. 1.32 (0.92, 1.88) 928. 329. Inf 0.0011
34 Stroke Stroke recency over 5 years Risperidone Users 53 339. 156. 1.32 (0.92, 1.88) 928. 329. Inf 0.0011
35 Stroke Stroke history Matched Controls 993 4284. 232. 1.28 (1.11, 1.46) 1020. 377. Inf 0.001
36 Stroke Stroke history Risperidone Users 268 907. 295. 1.28 (1.11, 1.46) 1020. 377. Inf 0.001
Discontinuation results
outcome subgroup Group N.events Person.years.at.risk Incidence_rate_per_1000_PY Adjusted_HR NNH Lower_CI_NNH Upper_CI_NNH ARR
1 Stroke CVD history Matched Controls 3278 44309. 74.0 1.26 (1.16, 1.36) 57.8 43.9 84.9 0.0173
2 Stroke CVD history Risperidone Users 707 7150. 98.9 1.26 (1.16, 1.36) 57.8 43.9 84.9 0.0173
3 Stroke HES stroke Matched Controls 4479 112584. 39.8 1.35 (1.26, 1.45) 75.6 62.6 95.4 0.0132
4 Stroke HES stroke Risperidone Users 1026 18229. 56.3 1.35 (1.26, 1.45) 75.6 62.6 95.4 0.0132
5 Stroke No CVD history Matched Controls 1201 68275. 17.6 1.62 (1.43, 1.84) 94.9 75.9 127. 0.0105
6 Stroke No CVD history Risperidone Users 319 11079. 28.8 1.62 (1.43, 1.84) 94.9 75.9 127. 0.0105
7 Stroke Pre-Covid period (Overall) Matched Controls 4302 103818. 41.4 1.32 (1.23, 1.41) 79.7 64.8 104. 0.0125
8 Stroke Pre-Covid period (Overall) Risperidone Users 982 17134. 57.3 1.32 (1.23, 1.41) 79.7 64.8 104. 0.0125
9 Stroke Pre-Covid period (No CVD history) Matched Controls 1154 63142. 18.3 1.59 (1.39, 1.80) 96.0 75.8 131. 0.0104
10 Stroke Pre-Covid period (No CVD history) Risperidone Users 306 10447. 29.3 1.59 (1.39, 1.80) 96.0 75.8 131. 0.0104
11 Stroke Pre-Covid period (No stroke history) Matched Controls 1942 91184. 21.3 1.47 (1.32, 1.62) 107. 85.4 144. 0.0093
12 Stroke Pre-Covid period (No stroke history) Risperidone Users 474 14985. 31.6 1.47 (1.32, 1.62) 107. 85.4 144. 0.0093
13 Stroke Pre-Covid period (CVD history) Matched Controls 3148 40676. 77.4 1.22 (1.12, 1.33) 63.3 46.3 100. 0.0158
14 Stroke Pre-Covid period (CVD history) Risperidone Users 676 6687. 101. 1.22 (1.12, 1.33) 63.3 46.3 100. 0.0158
15 Stroke Pre-Covid period (Stroke history) Matched Controls 2360 12634. 187. 1.20 (1.09, 1.32) 35.9 23.9 72.5 0.0278
16 Stroke Pre-Covid period (Stroke history) Risperidone Users 508 2149. 236. 1.20 (1.09, 1.32) 35.9 23.9 72.5 0.0278
17 Stroke all Matched Controls 4479 112584. 39.8 1.35 (1.26, 1.45) 75.6 62.6 95.4 0.0132
18 Stroke all Risperidone Users 1026 18229. 56.3 1.35 (1.26, 1.45) 75.6 62.6 95.4 0.0132
19 Stroke Stroke type - haemorrhagic Matched Controls 28 198. 141. 2.69 (1.64, 4.42) 6.31 4.33 11.6 0.158
20 Stroke Stroke type - haemorrhagic Risperidone Users 45 125. 359. 2.69 (1.64, 4.42) 6.31 4.33 11.6 0.158
21 Stroke Stroke type - ischaemic Matched Controls 1848 8615. 214. 1.24 (1.13, 1.37) 16.6 13.1 22.9 0.0601
22 Stroke Stroke type - ischaemic Risperidone Users 584 1886. 310. 1.24 (1.13, 1.37) 16.6 13.1 22.9 0.0601
23 Stroke No stroke history Matched Controls 2025 98709. 20.5 1.50 (1.36, 1.66) 104. 84.3 136. 0.0096
24 Stroke No stroke history Risperidone Users 495 15914. 31.1 1.50 (1.36, 1.66) 104. 84.3 136. 0.0096
25 Stroke Prescription age 65 - 74 years Matched Controls 439 13395. 32.8 1.47 (1.20, 1.82) 56.6 39.1 102. 0.0177
26 Stroke Prescription age 65 - 74 years Risperidone Users 118 2240. 52.7 1.47 (1.20, 1.82) 56.6 39.1 102. 0.0177
27 Stroke Prescription age 75 - 84 years Matched Controls 1974 52198. 37.8 1.33 (1.20, 1.48) 82.3 61.9 123. 0.0122
28 Stroke Prescription age 75 - 84 years Risperidone Users 452 8454. 53.5 1.33 (1.20, 1.48) 82.3 61.9 123. 0.0122
29 Stroke risperidone_Age_85+ Matched Controls 2066 46991. 44.0 1.34 (1.21, 1.48) 75.3 56.8 112. 0.0133
30 Stroke risperidone_Age_85+ Risperidone Users 456 7535. 60.5 1.34 (1.21, 1.48) 75.3 56.8 112. 0.0133
31 Stroke Stroke recency 1 - 5 years Matched Controls 384 2227. 172. 1.24 (1.03, 1.49) 29.2 17.0 103. 0.0342
32 Stroke Stroke recency 1 - 5 years Risperidone Users 179 811. 221. 1.24 (1.03, 1.49) 29.2 17.0 103. 0.0342
33 Stroke Stroke recency less than 1 year Matched Controls 172 354. 485. 1.07 (0.83, 1.38) 46.1 12.1 Inf 0.0217
34 Stroke Stroke recency less than 1 year Risperidone Users 121 208. 581. 1.07 (0.83, 1.38) 46.1 12.1 Inf 0.0217
35 Stroke Stroke recency over 5 years Matched Controls 297 2713. 109. 1.17 (0.93, 1.46) 76.0 31.1 Inf 0.0132
36 Stroke Stroke recency over 5 years Risperidone Users 118 902. 131. 1.17 (0.93, 1.46) 76.0 31.1 Inf 0.0132
37 Stroke Stroke history Matched Controls 2454 13875. 177. 1.23 (1.12, 1.35) 32.2 22.6 56.1 0.0311
38 Stroke Stroke history Risperidone Users 531 2315. 229. 1.23 (1.12, 1.35) 32.2 22.6 56.1 0.0311