Journal of Human Hypertension (1998) 12 , 73–74
1998 Stockton Press. All rights reserved 0950-9240/ 98 $12.00
COMMENTARY
IST and CAST: some answers but more
questions
R Path an sali an d PMW Bath
Kin gs College Hosp ital, Bessem er Road , Lon d on , UK
Keywords: acute stroke; aspirin; heparin; randomised controlled trials
Stroke is th e th ird m ost com m on cau se of d eath in com e w as looked at as a m ajor en d -p oin t. In th e IST
th e West an d th e com m on est cau se of ad u lt d is- 6-m on th ou tcom e figu res (Figu re 1), th ere w ere on ly
ability. 1 Un fortu n ately, efficaciou s treatm en ts h ave 1.3% m ore p eop le in d ep en d en t in th e asp irin grou p
rem ain ed elu sive 2 u n til recen tly. A n atu ral startin g com p ared w ith th e n on -asp irin grou p . Con trasts can
p oin t for d evelop in g treatm en ts for acu te isch aem ic be m ad e h ere w ith th e NINDS rt-PA 5 stu d y w h ere
stroke h as been to assess su ccessfu l th erap ies for th rom bolysis w as sh ow n to be associated w ith a 11–
an oth er vascu lar con d ition , m yocard ial in farction , 13% im p rovem en t in th e best clin ical ou tcom e w ith
in p articu lar asp irin , h ep arin an d th rom bolysis. a sim ilar n on -sign ifican t im p rovem en t in m ortality.
Th e qu estion w h eth er asp irin is first, ben eficial So it w ou ld seem th at rt-PA is u n d en iably m ore
an d secon d , safe in th e acu te stages of stroke h as effective. How ever, in favou r of asp irin is th e fact
been ad d ressed in tw o recen t m egatrials: th e In ter- th at on ly a sm all p rop ortion (,10% ) of p atien ts
n ation al Stroke Trial (IST)3 an d th e Ch in ese Acu te p resen tin g w ith isch aem ic stroke w ou ld satisfy cri-
Stroke Trial (CAST).4 Th e IST also looked at tw o teria for th e u se of th rom bolysis, com p ared w ith
d oses of su bcu tan eou s u n fraction ated h ep arin ; a asp irin w h ich cou ld be given to m ost (.90% ).6
‘ven ou s’ d ose of 5000 IU b.d . an d an ‘arterial’ d ose At first glan ce it w ou ld seem th at h ep arin w ou ld
of 12 500 IU b.d . Both trials h ad arou n d 20 000 h ave n o role in th e acu te treatm en t of stroke. In th e
p atien ts. IST h ad a 2×3 factorial d esign an d alth ou gh IST p rim ary ou tcom e m easu res (Table 1), th e sm all
ran d om ised w as n ot p lacebo-con trolled or blin d . acu te m ortality ben efit w as n ot reflected at 6 m on th s
CAST w as a p lacebo-con trolled an d d ou ble-blin d
trial of asp irin alon e. Table 1 Su m m ary of th e m ain trial ou tcom es, % even ts p re-
Th e asp irin resu lts from th e tw o trials w ere very ven ted . (All th e d ata is com bin ed in on e table bearin g in m in d
sim ilar (Table 1). Wh en takin g th e p rim ary ou tcom e d ifferen ces in treatm en t p eriod an d sp ecified ou tcom es in IST
m easu res, early d eath , an d later d eath or d ep en - an d CAST)
d en cy, th ere is a tren d tow ard m ortality red u ction
IS T CA S T
in th e acu te stages (ju st statistically sign ifican t in
CAST), an d a sm all ben efit is also seen in th e later
A sp vs N o Hep vs N o A sp vs N o
en d -p oin ts. How ever, it is on ly by com bin in g th e
trials an d th e early en d -p oin t w ith early recu rren t Prim ary ou tcom es
n on -fatal stroke th at a reason ably con vin cin g stat-
Death early 0.4 0.3 0.54
istical resu lt is obtain ed . By d oin g th is an absolu te 2 w eeks (IST) NS NS 2P = 0.04
red u ction (AR) in early d eath an d n on -fatal stroke 4 w eeks (CAST)
by 0.9% (2P = 0.001) an d late d eath an d d ep en d en cy
Death / Dep en d en ce 1.3 0 1.14
by 1.3% (2P = 0.01) is seen . By far th e m ost strikin g 6 m on th s (IST) NS NS NS
resu lt to com e from th ese trials is th e red u ction in Disch arge (CAST)
early recu rren t isch aem ic stroke w ith asp irin , an d
p resu m ably a large p art of th e later m ortality an d S econ d ary ou tcom es
d ep en d en cy ben efit w as d u e to th is. Th e acu te u se Recu rren t Isch aem ic 1.1 0.9 0.47
of asp irin can be recom m en d ed on th is basis, m ore Stroke 2P , 0.001 2P , 0.01 2P = 0.01
so th an for th e acu te treatm en t of th e in itial cere- Haem orrh agic −0.1 −0.8 −0.21
bral in farction . Stroke NS 2P , 0.00001 NS
Th is con clu sion w ou ld also ap p ly if a good ou t- All 0.9 0.2 0.16
2P , 0.001 NS NS
Corresp on d en ce: Dr Roh an Path an sali, Clin ical Research Fellow , Tran sfu sed or fatal 2P , 0.001 2P , 0.00001 2P = 0
Kin gs College Hosp ital, Bessem er Road , Lon d on , UK extracran ial bleed
Received an d accep ted 1 October 1997
1998 Stockton Press. All rights reserved 0950-9240/ 98 $12.00
COMMENTARY
IST and CAST: some answers but more
questions
R Path an sali an d PMW Bath
Kin gs College Hosp ital, Bessem er Road , Lon d on , UK
Keywords: acute stroke; aspirin; heparin; randomised controlled trials
Stroke is th e th ird m ost com m on cau se of d eath in com e w as looked at as a m ajor en d -p oin t. In th e IST
th e West an d th e com m on est cau se of ad u lt d is- 6-m on th ou tcom e figu res (Figu re 1), th ere w ere on ly
ability. 1 Un fortu n ately, efficaciou s treatm en ts h ave 1.3% m ore p eop le in d ep en d en t in th e asp irin grou p
rem ain ed elu sive 2 u n til recen tly. A n atu ral startin g com p ared w ith th e n on -asp irin grou p . Con trasts can
p oin t for d evelop in g treatm en ts for acu te isch aem ic be m ad e h ere w ith th e NINDS rt-PA 5 stu d y w h ere
stroke h as been to assess su ccessfu l th erap ies for th rom bolysis w as sh ow n to be associated w ith a 11–
an oth er vascu lar con d ition , m yocard ial in farction , 13% im p rovem en t in th e best clin ical ou tcom e w ith
in p articu lar asp irin , h ep arin an d th rom bolysis. a sim ilar n on -sign ifican t im p rovem en t in m ortality.
Th e qu estion w h eth er asp irin is first, ben eficial So it w ou ld seem th at rt-PA is u n d en iably m ore
an d secon d , safe in th e acu te stages of stroke h as effective. How ever, in favou r of asp irin is th e fact
been ad d ressed in tw o recen t m egatrials: th e In ter- th at on ly a sm all p rop ortion (,10% ) of p atien ts
n ation al Stroke Trial (IST)3 an d th e Ch in ese Acu te p resen tin g w ith isch aem ic stroke w ou ld satisfy cri-
Stroke Trial (CAST).4 Th e IST also looked at tw o teria for th e u se of th rom bolysis, com p ared w ith
d oses of su bcu tan eou s u n fraction ated h ep arin ; a asp irin w h ich cou ld be given to m ost (.90% ).6
‘ven ou s’ d ose of 5000 IU b.d . an d an ‘arterial’ d ose At first glan ce it w ou ld seem th at h ep arin w ou ld
of 12 500 IU b.d . Both trials h ad arou n d 20 000 h ave n o role in th e acu te treatm en t of stroke. In th e
p atien ts. IST h ad a 2×3 factorial d esign an d alth ou gh IST p rim ary ou tcom e m easu res (Table 1), th e sm all
ran d om ised w as n ot p lacebo-con trolled or blin d . acu te m ortality ben efit w as n ot reflected at 6 m on th s
CAST w as a p lacebo-con trolled an d d ou ble-blin d
trial of asp irin alon e. Table 1 Su m m ary of th e m ain trial ou tcom es, % even ts p re-
Th e asp irin resu lts from th e tw o trials w ere very ven ted . (All th e d ata is com bin ed in on e table bearin g in m in d
sim ilar (Table 1). Wh en takin g th e p rim ary ou tcom e d ifferen ces in treatm en t p eriod an d sp ecified ou tcom es in IST
m easu res, early d eath , an d later d eath or d ep en - an d CAST)
d en cy, th ere is a tren d tow ard m ortality red u ction
IS T CA S T
in th e acu te stages (ju st statistically sign ifican t in
CAST), an d a sm all ben efit is also seen in th e later
A sp vs N o Hep vs N o A sp vs N o
en d -p oin ts. How ever, it is on ly by com bin in g th e
trials an d th e early en d -p oin t w ith early recu rren t Prim ary ou tcom es
n on -fatal stroke th at a reason ably con vin cin g stat-
Death early 0.4 0.3 0.54
istical resu lt is obtain ed . By d oin g th is an absolu te 2 w eeks (IST) NS NS 2P = 0.04
red u ction (AR) in early d eath an d n on -fatal stroke 4 w eeks (CAST)
by 0.9% (2P = 0.001) an d late d eath an d d ep en d en cy
Death / Dep en d en ce 1.3 0 1.14
by 1.3% (2P = 0.01) is seen . By far th e m ost strikin g 6 m on th s (IST) NS NS NS
resu lt to com e from th ese trials is th e red u ction in Disch arge (CAST)
early recu rren t isch aem ic stroke w ith asp irin , an d
p resu m ably a large p art of th e later m ortality an d S econ d ary ou tcom es
d ep en d en cy ben efit w as d u e to th is. Th e acu te u se Recu rren t Isch aem ic 1.1 0.9 0.47
of asp irin can be recom m en d ed on th is basis, m ore Stroke 2P , 0.001 2P , 0.01 2P = 0.01
so th an for th e acu te treatm en t of th e in itial cere- Haem orrh agic −0.1 −0.8 −0.21
bral in farction . Stroke NS 2P , 0.00001 NS
Th is con clu sion w ou ld also ap p ly if a good ou t- All 0.9 0.2 0.16
2P , 0.001 NS NS
Corresp on d en ce: Dr Roh an Path an sali, Clin ical Research Fellow , Tran sfu sed or fatal 2P , 0.001 2P , 0.00001 2P = 0
Kin gs College Hosp ital, Bessem er Road , Lon d on , UK extracran ial bleed
Received an d accep ted 1 October 1997
