drug elution for all? the case against

DRUG ELUTION FOR ALL? DRUG ELUTION FOR ALL?

THE CASE AGAINSTTHE CASE AGAINST

Jim McLenachanJim McLenachan

Yorkshire Heart Centre,Yorkshire Heart Centre,

LeedsLeeds

DRUG ELUTING STENTSDRUG ELUTING STENTS

DO WE REALLY NEED THEM ?DO WE REALLY NEED THEM ?

DO THEY WORK ?DO THEY WORK ?

CAN WE SELECT “AT RISK” PATIENTS ?CAN WE SELECT “AT RISK” PATIENTS ?

ARE THEY SAFE ?ARE THEY SAFE ?

Stenting and procedures for Stenting and procedures for restenosis restenosis

(2000 data from 40 centres)(2000 data from 40 centres)

0

10

20

30

40

50

60

70

80

90

'92 '93 '94 '95 '96 '97 '98 '99 '00

Year

%

0

2

4

6

8

10

12

14

%

% Stent

% Restenosis

BCIS AUDIT

REPEAT PCI IN RAVELREPEAT PCI IN RAVEL

50556065707580859095

100

0 30 60 90 120 150 180 210 240 270 360

CYPHERBARE

EventFreeSurvival (%)

Days after implantation

N Engl J Med 2002;346:1773-80

CARDIAC EVENTS AT ONE YEARCARDIAC EVENTS AT ONE YEARRAVEL STUDYRAVEL STUDY

EVENTEVENT SIROLOMUS SIROLOMUS STENT STENT (n=120)(n=120)

BARE METAL BARE METAL STENT STENT (n=118)(n=118)

DEATHDEATH 22 22

Q WAVE MIQ WAVE MI 22 11

NON Q NON Q WAVE MIWAVE MI

22 44

CABGCABG 11 11

N Engl J Med 2002;346:1773-80

TIMING OF EVENTS IN RAVELTIMING OF EVENTS IN RAVEL

50556065707580859095

100

0 30 60 90 120 150 180 210 240 270 360

CYPHERBARE

EventFreeSurvival (%)

Days after implantation

N Engl J Med 2002;346:1773-80

REPEAT ANGIOGRAPHY

SIRIUS : Clinical eventsSIRIUS : Clinical events

All events to 360 daysAll events to 360 days

EVENTSEVENTS SIROLIMUS SIROLIMUS

n = 533n = 533CONTROLCONTROL

n = 525n = 525P valueP value

DEATHDEATH 1.3 (7)1.3 (7) 0.8 (4)0.8 (4) 0.5470.547

ALL MIALL MI 3.0 (16)3.0 (16) 3.4 (18)3.4 (18) 0.7300.730

NON-Q MINON-Q MI 2.3 (12)2.3 (12) 3.0 (16)3.0 (16) 0.4490.449

Holmes et al ACC 2003

SIRIUS : Clinical eventsSIRIUS : Clinical events

All events to 360 daysAll events to 360 days

EVENTSEVENTS SIROLIMUS SIROLIMUS

n = 533n = 533CONTROLCONTROL

n = 525n = 525P valueP value

DEATHDEATH 1.3 (7)1.3 (7) 0.8 (4)0.8 (4) 0.5470.547

ALL MIALL MI 3.0 (16)3.0 (16) 3.4 (18)3.4 (18) 0.7300.730

NON-Q MINON-Q MI 2.3 (12)2.3 (12) 3.0 (16)3.0 (16) 0.4490.449

TLRTLR 4.9 (26)4.9 (26) 20.0 (105)20.0 (105) < 0.001< 0.001

MACEMACE 8.3 (44)8.3 (44) 22.3 (117)22.3 (117) < 0.001< 0.001

Holmes et al ACC 2003

DRUG ELUTING STENTSDRUG ELUTING STENTS

DO WE REALLY NEED THEM ?DO WE REALLY NEED THEM ?

DO THEY WORK ?DO THEY WORK ?

CAN WE SELECT “AT RISK” PATIENTS ?CAN WE SELECT “AT RISK” PATIENTS ?

ARE THEY SAFE ?ARE THEY SAFE ?

DRUG ELUTING STENTSDRUG ELUTING STENTS

DO WE REALLY NEED THEM ?DO WE REALLY NEED THEM ?

DO THEY WORK ?DO THEY WORK ?

CAN WE SELECT “AT RISK” PATIENTS ?CAN WE SELECT “AT RISK” PATIENTS ?

ARE THEY SAFE ?ARE THEY SAFE ?

PREDICTION OF RESTENOSIS PREDICTION OF RESTENOSIS (%)(%)

StentStent

Length Length (mm)(mm)

Post-procedure In-stent MLD (mm)Post-procedure In-stent MLD (mm)

2.502.50 2.752.75 3.003.00 3.253.25 3.503.50 3.753.75

88 16.416.4 12.312.3 9.29.2 6.86.8 5.05.0 3.63.6

1515 21.521.5 16.516.5 12.412.4 9.39.3 6.86.8 5.05.0

1818 24.024.0 18.518.5 14.114.1 10.510.5 7.87.8 5.85.8

2525 30.730.7 24.224.2 18.718.7 14.214.2 10.610.6 7.97.9

2828 33.933.9 26.926.9 21.021.0 16.016.0 12.112.1 9.09.0

3535 41.841.8 34.034.0 27.127.1 21.121.1 16.116.1 12.112.1KEREIAKES Am J Cardiol 2000;86:336

DRUG ELUTING STENTSDRUG ELUTING STENTS

DO WE REALLY NEED THEM ?DO WE REALLY NEED THEM ?

DO THEY WORK ?DO THEY WORK ?

CAN WE SELECT “AT RISK” PATIENTS ?CAN WE SELECT “AT RISK” PATIENTS ?

ARE THEY SAFE ?ARE THEY SAFE ?

Binary Restenosis (%)Binary Restenosis (%)

p<0.001 83%

p<0.001 83%

SCORE TrialBinary Restenosis (%)SCORE TrialBinary Restenosis (%)

SAT (%)SAT (%)

SCORE TrialMACE (6 months)SCORE TrialMACE (6 months)

AMI (%)AMI (%) Death (%)Death (%)

Subacute thrombosis andSubacute thrombosis and drug eluting stents drug eluting stents Is there a link? Is there a link?

Stent thrombosis at 56 hoursStent thrombosis at 56 hours

FDA ALERT FDA ALERT 2929thth October, 2002 October, 2002

FDA Advises Physicians of Adverse Events FDA Advises Physicians of Adverse Events Associated with Cordis Cypher Coronary Stents Associated with Cordis Cypher Coronary Stents

FDA has received more than 290 reports of FDA has received more than 290 reports of thrombosis (clotting) occurring one to 30 days after thrombosis (clotting) occurring one to 30 days after the procedure to implant the device. In more than 60 the procedure to implant the device. In more than 60 of these reports, use of the device was associated of these reports, use of the device was associated with the death of the patient; with the death of the patient;

FDA has also received more than 50 reports, FDA has also received more than 50 reports,

including some deaths, that Cordis considers to be including some deaths, that Cordis considers to be possible hypersensitivity reactions.possible hypersensitivity reactions.

Virmani R, Guagliumi G, Farb AVirmani R, Guagliumi G, Farb A

E-Sirius (male 59 yrs)

Two Cypher Stents (3.0 x 18mm + 2.5 x 18mm)

E-Sirius (male 59 yrs)

Two Cypher Stents (3.0 x 18mm + 2.5 x 18mm)

Marked Chronic Inflammation and Medial DestructionMarked Chronic Inflammation and Medial Destruction

Aneurysm

ProximalStentProximalStent

Distal StentDistal Stent

Prominent eosinophils Prominent eosinophils Inflammation within and surrounding stent struts and in adventitia Inflammation within and surrounding stent struts and in adventitia

Eosinophils in adventitia (red colored cells, Luna stain)Eosinophils in adventitia (red colored cells, Luna stain)

Giant cells surrounding foreign material in aneurysmGiant cells surrounding foreign material in aneurysm

Polymer coating around stent strutPolymer coating around stent strut

Inflammatory sequelae to what?Long Term Human Pathology: 18 Months

Inflammatory sequelae to what?Long Term Human Pathology: 18 Months

Virmani R, Guagliumi G, Farb AVirmani R, Guagliumi G, Farb A

LONG SEGMENT OF LAD LONG SEGMENT OF LAD DISEASEDISEASE

AFTER 2 TAXUS STENTSAFTER 2 TAXUS STENTS

4 MONTHS LATER4 MONTHS LATER

CARDIAC EVENTS AT TWO YEARSCARDIAC EVENTS AT TWO YEARSRAVEL STUDYRAVEL STUDY

EVENTEVENT SIROLOMUS SIROLOMUS STENT STENT (n=120)(n=120)

BARE METAL BARE METAL STENT STENT (n=118)(n=118)

DEATHDEATH 6 (5.0%)6 (5.0%) 3 (2.5%)3 (2.5%)

Q WAVE MIQ WAVE MI 2 (1.7%)2 (1.7%) 0 (0%)0 (0%)

NON Q NON Q WAVE MIWAVE MI

1 (0.8%)1 (0.8%) 4 (3.4%)4 (3.4%)

CABGCABG 2 (1.7%)2 (1.7%) 0 (0%)0 (0%)

MORICE et al ACC 2003

CYPHERCYPHERMortality from Randomized trialsMortality from Randomized trials

CYPHERCYPHER Bx-VelocityBx-Velocity

SIRIUS SIRIUS

(1 year)(1 year) 7 /5337 /533 4/5254/525

C-SIRIUS C-SIRIUS

(9 months)(9 months) 0 / 500 / 50 0 / 500 / 50

E-SIRIUS E-SIRIUS

(9 months)(9 months) 2 / 1752 / 175 1 / 1771 / 177

RAVEL RAVEL

(2 years)(2 years) 6 / 1206 / 120 3 / 1183 / 118

TOTALS TOTALS 15 / 87815 / 878

(1.71%)(1.71%) 8 / 8708 / 870

(0.92%)(0.92%)

“Selective use of drug eluting stents can further improve the already excellent outcome seen with regular stent technology.”

Spencer B King III,Circulation 2003;108:248-249

“ As to diseases, make a habit of two things – to help, or at least do no harm.”

HIPPOCRATES

““I think there isI think there is something to this something to this inflammation story”inflammation story”

K. DAWKINS, LONDON, 5/12/03K. DAWKINS, LONDON, 5/12/03

DRUG ELUTING STENTSDRUG ELUTING STENTS

DO WE REALLY NEED THEM ?DO WE REALLY NEED THEM ?

DO THEY WORK ?DO THEY WORK ?

CAN WE SELECT “AT RISK” PATIENTS ?CAN WE SELECT “AT RISK” PATIENTS ?

ARE THEY SAFE ?ARE THEY SAFE ?

IAIN SIMPSONIAIN SIMPSON

ANDAND

SOUTHAMPTONSOUTHAMPTON

PRIMARY PCI FOR AMI DEBATE,PRIMARY PCI FOR AMI DEBATE,BRIGHTON 24 th October. 2003BRIGHTON 24 th October. 2003

Dr Liam Penny Dr Liam Penny

V.V.

Dr Alison CalverDr Alison Calver

SIMPO !! - 1980

““In no other walk of life does the cloven hoof In no other walk of life does the cloven hoof so quickly display itself. Golf is the infallible test. so quickly display itself. Golf is the infallible test. The man who can go into a patch of rough alone, The man who can go into a patch of rough alone, with the knowledge that only God is watching him, with the knowledge that only God is watching him, and play his ball where it lies, is the man who will and play his ball where it lies, is the man who will serve you faithfully and well. But the man who is serve you faithfully and well. But the man who is hasty, unbalanced and violent on the links, will display hasty, unbalanced and violent on the links, will display the same qualities in the wider field of everyday life.”the same qualities in the wider field of everyday life.”

PG WodehousePG Wodehouse