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Transcript of Drug Eluting Stents - bcis.org.uk .Drug Eluting Stents overhyped, overused and overpriced? William

  • Drug Eluting Stents overhyped, overused and overpriced?

    William Wijns MD, PhD Cardiovascular Center Aalst

    http://www.cardio-aalst.be

    William.Wijns@village.uunet.be

    Advanced Angioplasty 2008 BCIS 23rd Jan 2008

  • What did we expect from DES ?

    Eliminate restenosis, at last . . . Improve durability of the results of PCI thereby justifying expanding indications

    Allow vessel healing and endothelialisation, without interfering with normal vessel biology

    Avoid any systemic side effects Be affordable . . .

  • Expected Gradient in Clinical Outcome as a function of Lesion / Patient Complexity

    Adapted from E.R. Edelman, C. Rogers, Circ. 1999; 100:896-8

    10

    20

    30

    40

    Clin

    ical

    Fai

    lure

    rate

    [%]

    BMS 1

    DES 2

    DES 1

    FIM Randomized Clinical Trials Registries Real Life

    Lesion / Patient complexity

  • Efficacy of Sirolimus- and Paclitaxel-Eluting Coronary Stents

    Stone GW et al, NEJM 2007;356:998-1008

    Gradient = 15.8% Gradient = 9.9%

    PES SES

  • Long-Term Outcomes with Drug-Eluting Stents vs Bare-Metal Stents in Sweden

    Lagerqvist et al, NEJM 2007;356:1009-1019

  • The Rotterdam experience with 100% DES use

    - Sequential monocentric registry

    - Systematic use of one DES brand

    - Comparison with historical* controls

    Revascularisation GRADIENT

    BMS vs Cypher 6.7 % at 1 year

    8.3 % at 2 years

    BMS vs Taxus 5.0 % at 1 year

    * Worse patient / lesion characteristics in DES era

  • Why did the Edelman-Rogers model not work?

    Randomised clinical trials were designed to maximise the outcome gradient between DES and BMS, in order to provide the evidence that DES should replace BMS and be used in all cases

    The performance of BMS used in DES trials is perceived by many as exceedingly poor compared to their experience (EU > US)

    Per protocol angiography results in doubling of TLR rates, even after adjustement for clinically-driven TLR (oculo-stenotic reflex)

  • SCAAR UCR

    SWEDEN 2007

    Years after PCI 3 2 1 0

    Cum

    ulat

    ive

    prob

    abili

    ty o

    f res

    teno

    sis

    0,10

    0,08

    0,06

    0,04

    0,02

    0,00

    DES

    Work horse BMS

    Less well studied BMS

    Clinical restenosis

  • What did we expect from DES ?

    Eliminate restenosis, at last . . . Improve durability of the results of PCI thereby justifying expanding indications

    Allow vessel healing and endothelialisation, without interfering with normal vessel biology

    Avoid any systemic side effects Be affordable . . .

  • LAD 6 months following SES

    Hofma et al. Eur Heart J 2006;27:166-170

  • Ach response 6 m following SES

    Hofma et al. Eur Heart J 2006;27:166-170

  • After intracoronary nitrates

    Hofma et al. Eur Heart J 2006;27:166-170

  • Baseline Pacing 1 2 3 4

    Flow-Mediated, Endothelium-Dependent Epicardial Vasomotor Changes

    Pacing Protocol*

    min

    ISDN IC

    Nitrates

    Coronary Angiography

    QCA reference vessel, stented vessel (proximal, distal) * Stop vasoactive drugs 24 hours

  • Change in Vessel Diameter (% from Baseline)

    -10

    0

    10

    20

    30

    BMS n = 8

    Pacing ISDN -10

    0

    10

    20

    30

    DES A n = 17

    Pacing ISDN -10

    0

    10

    20

    30

    DES B n = 9

    Pacing ISDN

    Reference Vessel

    Distal segment stented vessel

  • Change in Vessel Diameter (% from Baseline)

    -10

    0

    10

    20

    30

    BMS n = 8

    Pacing ISDN -10

    0

    10

    20

    30

    DES C n = 5

    Pacing ISDN -10

    0

    10

    20

    30

    DES D n = 23

    Pacing ISDN

    Reference Vessel

    Distal segment stented vessel

  • Flow-mediated vasodilation is observed 6-9 months after bare metal stenting in segments proximal and distal to the stent Vasomotor responses to increased flow vary from vasoconstriction to vasodilatation with different DES brands while non-endothelial dependent dilation to nitrates is maintained Some drug-polymer-device combinations exert durable toxic effects on the endothelium at a distance from the implant

    Summary of findings

  • Maintaining patients at higher risk of thrombosis on dual antiplatelet therapy (DAPT) forever has no scientific foundation yet

    There is some benefit associated with the extension of DAPT from 6 months up to 1 year (Eisenstein et al. JAMA 2007;297:159-68), a practice now endorsed by FDA and by the ESC PCI Guidelines (in the absence of increased risk for bleeding)

    Outcomes may improve with better patient compliance, from a better understanding and identification of non-responders and with the availability of more potent antiplatelet agents. However, at the expense of excess bleeding (Triton)

    Maintaining patients on long term DAPT is disruptive of other medical and surgical practices, as readily apparent in elderly patients with multiple co-morbidities

    Solving the late thrombosis issue will be mandatory because trying to mask it will not be sustainable for the long term

    Thienopyridines for ever ?

  • What did we expect from DES ?

    Eliminate restenosis, at last . . . Improve durability of the results of PCI thereby justifying expanding indications

    Allow vessel healing and endothelialisation, without interfering with vessel biology

    Avoid any systemic side effects Be affordable . . .

  • Overall mortality

  • Cardiac death

  • Health Technology Assessment

    I. HTA analyses are necessarily unfavorable given the lack of mortality reduction, as opposed to drugs or other devices

    II. All HTA analyses (NICE, Ontario, Belgian KCE) indicate exceedingly high incremental costs to avoid one TLR event

    III. NNT to avoid restenosis events depend on the background risk of recurrence with BMS. Absolute risk reduction is what matters ...

  • Drug Eluting Stents overhyped, overused and overpriced?

    Are these the real issues ?

  • Drug Eluting Stents overhyped, overused and overpriced?

    The real challenges are

    to recover our credibiliy to restore professional leadership to protect our freedom to operate

  • The SCAAR registry or the Swedish yo-yo

    PW Serruys, J Daemen, EuroIntervention 2007;3:297

    The impact of the NEJM on the Swedish medical practice resulted in a drop of the DES use to less than 20%,a phenomenon which has been sarcastically coined the Swedish yo-yo. It is a heavy responsability for our Swedish colleagues to assess the result of this drop in DES-use.

  • The SCAAR registry or the Swedish yo-yo

    PW Serruys, J Daemen, EuroIntervention 2007;3:297 What about the data yo-yo ? - September 2006, Barcelona: safety concern ? - New analyses up to Stettler, 2007: no fire, neutral effect of DES on death and infarction rates up to 4 years, even in high-risk such as diabetes (!) and off label indications

    - September 2007, Vienna: 6-fold increase in adjusted OR for out of hospital mortality in STEMI patients treated with DES

    - October 2007, TCT: DES are saving lives

  • The SCAAR registry or the Swedish yo-yo

    PW Serruys, J Daemen, EuroIntervention 2007;3:297 What about the data yo-yo ? Why do we seem to care more about devices and technicalities than about patients ?

  • The SCAAR registry or the Swedish yo-yo

    PW Serruys, J Daemen, EuroIntervention 2007;3:297 What about the data yo-yo ? Why do we seem to care more about devices and technicalities than about patients ?

    Despite the plethora of trials and registries, essential patient-oriented questions remain unanswered. Why so few patient-oriented trials ?

  • The SCAAR registry or the Swedish yo-yo

    PW Serruys, J Daemen, EuroIntervention 2007;3:297 What about the data yo-yo ? Why do we seem to care more about devices

    and technicalities than about patients ?

    Despite the plethora of trials and registries, essential patient-oriented questions remain unanswered. Why so few patient-oriented trials ?

    Why do we not focus on the life-saving indications of PCI that represent most of our activity ?

  • 48 %

    22 %

    STABLE Class I A

    If large ischemic area

    NSTEMI ACS Class I A

    Clinical Indications for PCI Euro Heart Survey

    30 %

    STEMI Class I A

    6789 Patients across Europe

  • Drug Eluting Stents overhyped, overused and overpriced?

    The real challenges are

    to recover our credibiliy to restore professional leadership to protect our freedom to operate

  • Grants/Research: Investigator, co-PI or PI in trials for several device (Abbott, Biosensors, Biotronik, Boston Scientific, Cappella, Conor, Cordis J&J, Devax, Medtronic, Orbus Neich, Sorin, Terumo, Topspin, Volcano) and pharmaceutical (BMS, GSK, Therabel) companies

    All Consulting Fees, Honoraria and Research Grants go to the Cardiovascular Research Aalst Foundation (non profit organisation)

    Speakers Bureau: NONE

    Equity Interests/Stock Options/Major-Minor Stock Shareholder: NONE

    Royalty Income: NONE

    Ownership/Founder/Co-Founder: Cardiovascular Research Aalst Foundation co-founder of Cardio3, biotechnology start-up on Cell Therapy

    Disclosures for W. Wijns Ca