DRUG ELUTION FOR ALL? THE CASE AGAINST Jim McLenachan Yorkshire Heart Centre, Leeds

DRUG 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 restenosis (2000 data from 40 centres) BCIS AUDIT

REPEAT PCI IN RAVEL REPEAT PCI IN RAVEL Event Free Survival (%) Days after implantation N Engl J Med 2002;346:

CARDIAC EVENTS AT ONE YEAR RAVEL STUDY EVENT SIROLOMUS STENT (n=120) BARE METAL STENT (n=118) DEATH 2 2 Q WAVE MI 2 1 NON Q WAVE MI 2 4 CABG 1 1 N Engl J Med 2002;346:

TIMING OF EVENTS IN RAVEL Event Free Survival (%) Days after implantation N Engl J Med 2002;346: REPEAT ANGIOGRAPHY

SIRIUS : Clinical events All events to 360 days All events to 360 days EVENTSSIROLIMUS n = 533 CONTROL n = 525 P value DEATH 1.3 (7) 0.8 (4) ALL MI 3.0 (16) 3.4 (18) NON-Q MI 2.3 (12) 3.0 (16) Holmes et al ACC 2003

SIRIUS : Clinical events All events to 360 days All events to 360 days EVENTSSIROLIMUS n = 533 CONTROL n = 525 P value DEATH 1.3 (7) 0.8 (4) ALL MI 3.0 (16) 3.4 (18) NON-Q MI 2.3 (12) 3.0 (16) TLR 4.9 (26) 20.0 (105) < MACE 8.3 (44) 22.3 (117) < Holmes et al ACC 2003

DRUG 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 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 (%) Stent Length (mm) Post-procedure In-stent MLD (mm) KEREIAKES Am J Cardiol 2000;86:336

DRUG 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 (%) p<0.001  83% SCORE Trial Binary Restenosis (%) SCORE Trial Binary Restenosis (%)

SAT (%) SCORE Trial MACE (6 months) SCORE Trial MACE (6 months) AMI (%) Death (%)

Subacute thrombosis and drug eluting stents Is there a link?

Stent thrombosis at 56 hours

FDA ALERT 29 th October, 2002 FDA Advises Physicians of Adverse Events Associated with Cordis Cypher Coronary Stents FDA Advises Physicians of Adverse Events Associated with Cordis Cypher Coronary Stents FDA has received more than 290 reports of thrombosis (clotting) occurring one to 30 days after the procedure to implant the device. In more than 60 of these reports, use of the device was associated with the death of the patient; FDA has received more than 290 reports of thrombosis (clotting) occurring one to 30 days after the procedure to implant the device. In more than 60 of these reports, use of the device was associated with the death of the patient; FDA has also received more than 50 reports, including some deaths, that Cordis considers to be possible hypersensitivity reactions. FDA has also received more than 50 reports, including some deaths, that Cordis considers to be possible hypersensitivity reactions.

Virmani R, Guagliumi G, Farb A E-Sirius (male 59 yrs) Two Cypher Stents (3.0 x 18mm x 18mm) E-Sirius (male 59 yrs) Two Cypher Stents (3.0 x 18mm x 18mm)

Marked Chronic Inflammation and Medial Destruction Aneurysm Proximal Stent Proximal Stent Distal Stent Distal Stent Prominent eosinophils Inflammation within and surrounding stent struts and in adventitia

Eosinophils in adventitia (red colored cells, Luna stain) Giant cells surrounding foreign material in aneurysm Polymer 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 A

LONG SEGMENT OF LAD DISEASE

AFTER 2 TAXUS STENTS

4 MONTHS LATER

CARDIAC EVENTS AT TWO YEARS RAVEL STUDY EVENT SIROLOMUS STENT (n=120) BARE METAL STENT (n=118) DEATH 6 (5.0%) 6 (5.0%) 3 (2.5%) 3 (2.5%) Q WAVE MI 2 (1.7%) 2 (1.7%) 0 (0%) 0 (0%) NON Q WAVE MI 1 (0.8%) 1 (0.8%) 4 (3.4%) 4 (3.4%) CABG 2 (1.7%) 2 (1.7%) 0 (0%) 0 (0%) MORICE et al ACC 2003

CYPHER Mortality from Randomized trials CYPHER CYPHERBx-Velocity SIRIUS (1 year) 7 /533 7 /533 4/525 4/525 C-SIRIUS (9 months) 0 / 50 0 / 50 E-SIRIUS (9 months) 2 / / / / 177 RAVEL (2 years) 6 / / / / 118 TOTALS 15 / / 878 (1.71%) (1.71%) 8 / / 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:

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

“I think there is something to this something to this inflammation story” K. DAWKINS, LONDON, 5/12/03

DRUG 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 SIMPSON IAIN SIMPSON AND ANDSOUTHAMPTON

PRIMARY PCI FOR AMI DEBATE, BRIGHTON 24 th October Dr Liam Penny V. V. Dr Alison Calver

SIMPO !!

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