Ontarget Results

8/17/2019 Ontarget Results

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TARGET

ONTARGET: The ONgoing Telmisartan Alone

and in Combination with Ramipril GlobalEndpoint Trial


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TARGET

Background

• ACE-inhibitors (e.g. ramipril in the HOE trial!

red"#es C$ death% &'% stroe and H) hosp in

those with C$* or *& in the absen#e o+

,entri#"lar ds+"n#tion or heart +ail"re• ACE-inhibitors are not tolerated b /0 to 1/0

o+ patients

• 2ill an AR3 (telmisartan! be as e++e#ti,e and

better tolerated4

• 's the #ombination s"perior4


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ONTARGET

Questions:.'s telmisartan 5non-in+erior6 to ramipril4

1.'s the #ombination s"perior to ramipril4

Outcome:

.rimar: C$ death% &'% stroe% CH) hosp

1.7e se#ondar: C$ death% &'% stroe (HOE trial o"t#ome!Design:

8ingle blind r"n-in (n91%;!

Randomi


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TARGET

Study Organization

Study Popuation: Barge Randomi


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TARGET


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TARGET

Et"nicity

Ot"er #$

B A%r#$Ot"As

&$St"As

'$

(atin

)$

European

!"in)$

Ot"er

'$

BA%r #$

Ot"

*$

St"As

#$(atin

+$

European

!"

*

ONTARGET,TRANS!END -OPE


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TARGET

Eigi.iity !riteria

/ncusion:

// ears or older with one

o+ the +ollowing

Coronar arter disease

eripheral arter disease

Cerebro,as#"lar disease

High ris diabetes with

e,iden#e o+ end-organ

damage

E0cusion:

'nabilit to dis#ontin"e%

hpersensiti,it or intoleran#e to%

ACE inhibitors or AR3

8mptomati# CH) signi+i#ant

primar ,al,"lar or o"t+low tra#tobstr"#tion #onstri#ti,e peri#arditis

sn#ope "nnown etiolog% CA3G

or C' I > mths "n#ontrolled

hpertension

8igni+i#ant renal arter stenosis

hepati# ds+"n#tion

Other medi#al #onditions or so#ial

reasons


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TARGET

1ey Baseine !"aracteristics

Ramipril Telmisartan Combination

N /=@ /?1 /;1

Age @@.? @@.? @@./

0 +emales 1=.1 1@.> 1@./

0 CA* =?.? =?./ =?.=

0 8troeT'A 1.; 1;.@ 1;.

0 *iabetes >@.= >.; >=.

3 ?.1. ?.=1. ?.1.

8tatins @.; @1.; @.

Antiplatelet ;./ . .

β-blo#er /@./ /@. /=.?


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TARGET

!"ange in BP 2mm-g3

Ramipril Telmisartan Combination

8stoli# -@.; -@. -.?

*iastoli# -?.@ -/.1 -@.;


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TARGET

Statistica !onsiderations

'n HOE the ha

)or non-in+eriorit (Telmisartan , ramipril! the one-sided =./0 C' sho"ld be below

.>. Ass"ming an ann"al e,ent rate o+ >.=0% =;; patients per gro"p +ollowed +or ?./rs pro,ided :

-0 power +or N' (T , R!

->0 power s"periorit (T J R , R!

Total randomi


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Possi.e resuts %or t"e end o% t"e Tria %or

ONTARGET Non4/n%eriority !omparison

;.= .; .=

Telmisartanbetter Ramipril better N o n - i n + e r i o r i t & a r g i n

(!

(1!(>!

RR(:/0C'!Case(! - point estimatewith:/0C' pro,esTisKnon-in+eriorK thanRCase(1! - point estimatewith:/0C' +ailstopro,eTisKnon-in+eriorK toRCase(>! - point estimatewith:/0C' pro,esTisKin+erior toR TARGET


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TARGET

Study 5edications Titration

Run4in 2Singe Bind3

Day '46 Ram #7& mg 8 Te Pace.o

Day 94'* Ram #7& mg 8 Te 9* mg

Day ''4' Ram &7* mg 8 Te 9* mg

Randomization 2Dou.e Bind3

# ;eeks Ram Pace.o 8 Te * mg

Ram & mg 8 Te Pace.o

Ram & mg 8 Te * mg

T"en


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TARGET Reasons %or Not

Randomizing Patients0

R"n-in Completed (n91%;! ;;

Not Randomi


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TARGET

Randomized On Study Ram On Study Te

' >ear )7& )#76

# >ear &7+ 7

9 >ear '7? 979


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TARGET

Temisartan s Ramipri


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R % P t


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TARGET Reasons %or Permanenty

Stopping Study 5edications

RamN&?+

TeN&9#

Te s7 RamRR P

-ypotension '9) ##) '7&9 *7***'

Syncope '& ') '7#? *79&*

!oug" 6+* )6 *7#+ C*7***'

Diarr"ea '# ') '7&) *7#*

Angioedema #& '* *79* *7*''&

Rena

/mpairment

+* + '7'9 *79+

AnyDiscontinuation

#*)) ')+# *7)9 *7*#

P i O t -OPE


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TARGET Primary Outcome -OPE

Primary Outcome

Ram Tel Tel ,s RamN (0! N (0! RR (/0 C'! (non-in

N /=@ /?1

rimar O"t#ome

C$ *eath% &'% 8troe%CH) Hosp

?1(@.?@0!

?1>(@.@@0!

.; (;.?-.;! ;.;;>

(Ad"sted +or 83! .;1 (;./-.;! ;.;;//

HOE rimar O"t#ome

C$ *eath% &'% 8troe 1;

(?.0!

;

(>.>0!

;. (;.-.;=! ;.;;;

(Ad"sted +or 83! ;. (;.-.;=! ;.;;1

ONTARGET Non /n%eriority


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ONTARGET Non4/n%eriority

!omparison

;.A;.:.;..1RR:/0C'

N o n - i n + e r i o r i t & a r g i n

rimarComposite (p9;.;;?!

C$*eath &' 8troe(HOEComposite! (p9I;.;;!

Telmisartanbetter Ramipril better

TARGET

ONTARGET Non /n%eriority


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;.@;.=;.;.:.;..1.>.?RR:/0C'

C$*eath&'8troeCH)Hosp

All *eathTelmisartanbetter Ramipril better

ONTARGET Non4/n%eriority

!omparison

TARGET

Time to Primar O tcome


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Time to Primary Outcome

Learso+ )ollow-"

TelmisartanRamipril

; . ;

; . ; / ; . ; ; . / ; . 1 ; ; . 1 /

; 1 > ?

TelmisartanRamipril

RA/=@A1? =A>1 =?=> =;:/

TARGET

Pre speci%ied S .gro p Ana sis


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;.= .; .>

RR (/0 C'! in Telmisartan Gro"

Telmisartan better Ramipril better

Primary !omposite

-0 o% !@DNo -0 o% !@D

SBP C '69'69 4 '&* '&*

Dia.etesNo Dia.etes

(o; Risk5edium Risk -ig" Risk

Age C +&+& 4 ?& ?&

5ae


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TARGET !oncusions: Temisartan

s7 Ramipri 2'3

. Telmisartan is #learl 5non-in+erior6 to ramipril• rimar #omposite o"t#ome (p9;.;;>!• HOE primar o"t#ome (p9;.;;!

&ost (;0! o+ the bene+its o+ ramipril arepreser,ed

1. Consistent res"lts on a range o+:

• 8e#ondar o"t#omes• 8"bgro"ps

!oncusions: Temisartan


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TARGET !oncusions: Temisartan

s7 Ramipri 2#3

>. 8ensiti,it analsis "sing a per proto#ol approa#h

#on+irms this

?. Telmisartan eDhibits slightl s"perior tolerabilit• Bess #o"gh and angione"roti# edema• &ore mild hpotensi,e smptoms% b"t no

di++eren#e in se,ere hpotensi,e smptoms

s"#h as sn#ope


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TARGET

!om.ination s Ramipri



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Learso+ )ollow-"

; . ;

; . ; / ; . ; ; . / ; . 1 ; ; . 1 /

; 1 > ?

RamiprilTel. Ram.

RA/=@A1? =A>1 =?=> =;:/TRA/;1A>? ==?; =>== =;1>

TARGET

E%%icacy !omparison


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;.?;.@;..;.1.?.@

Composite (p9;./;?!C$*eath

&'8troe

CH)HospRamipril JTelmisartanbetter Ramipril better RR:/0C'

E%%icacy !omparison TARGET

Te 8 Ram Ram: Pre4speci%ied Su.groups


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;.= .; .>

Relati,e Ris in Ramipril Telmisartan Gro"p

(/0 Con+iden#e 'nter,al!

Ramipril Telmisartanbetter

Ramipril better

Primary !omposite

-0 o% !@DNo -0 o% !@D

SBP C '69

'69 C SBP C '&*

SBP '&*

Dia.etes

No Dia.etes

-OPE (o; Risk Score

-OPE 5edium Risk Score

-OPE -ig" Risk Score

Age C +&

+& C Age C ?&

Age ?&

5ae


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Time to Permanent Discontinuation

o% Study 5edication

Learso+ )ollow-"

C " m " l a t i , e H a

; . ?

; 1 > ?

RamiprilTel. Ram.

Mat RisLr Lr 1 Lr > Lr ?R/=@==@ =@/ @@ @1/?TR/;1=@?1 =;/ @@? @1?1


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/ i ti


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TARGET

/mpications

• Telmisartan is as e++e#ti,e as ramipril% with a

slightl better tolerabilit.

• Combination therap is not s"perior to

ramipril% and has in#reased side e++e#ts.

Ontarget Results

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