my conflicts of interest are…

Ground breaking, Life changing™

Cardiology

Cypher in AMI

Summary of Trial Evidence

Dr Steve FearnDirector of Health Economics and Medical Affairs

Cordis UK

My conflicts of interest are…

• I am employed by Cordis

• I hold J&J stock

Approved indications

• Cypher has a specific CE mark for use in AMI.

• Also:– De novo lesions– In-stent restenosis– Small vessels (to 2.25mm)– Diabetes– Multivessel disease– Bifurcations– CTO– Infrapopliteal lesions

Important Questions

• Is Cypher safe in AMI patients

– Death, further MI, stent thrombosis?

• Does Cypher reduce the rate of repeat revascularisation?

• What about the longer-term?

• What about cost-effectiveness

Most Recent Data Synthesis

Kastrati et al EHJ 2007;28:2706-13

Diaz de la Llera

120 65.5 SES Death, MI or TVR1m BMS

9m SES

12m

(planned)

MULTI-STRATEGY

744 63.8 SES Death, MI or TVR 3m8m

(planned)

Abstracts

Detailed summary data on 2,381 patients randomised to BMS or Cypher


Cardiology

Cypher-specific Trials

N 744 175 320 712 310 120

Follow up 8m 1Y 1Y 1Y 1Y 1Y

Months planned dual APT 3 3 12 6 12 9

Cypher in AMI: All-cause Mortality

All-cause Mortality

3.0%

8.0%

1.9%1.3%

5.0%

4.0%

9.1%

4.4%

2.6%3.3%

2.3% 2.2%

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

10%

MULT

ISTRATEG

Y

STRATEGY

SESAMI

TYPHOO

N

MIS

SION

Diaz d

e la

Llera

Eve

nt R

ate

Cypher

BMS

Cypher in AMI: All-cause Mortality

Study nameOutcomeTime pointStatistics for each studyEvents / TotalOdds ratio and 95% CI

Odds Lower Upper ratiolimitlimitCypherBMS

STRATEGYDeath12m0.880.302.537 / 878 / 88

SESAMIDeath12m0.420.111.643 / 1607 / 160

TYPHOONDeath12m1.010.372.718 / 3558 / 357

MISSIONDeath12m0.470.092.632 / 1584 / 152

Diaz et alDeath12m1.530.259.483 / 602 / 60

MULTISTRATEGYDeath8m 0.730.331.6011 / 37215 / 372

0.770.491.2234 / 119244 / 1189

0.10.2 0.5 1 2 5 10

Favours CypherFavours BMS

Meta Analysis

p (overall effect) = 0.27Heterogeneity (I2) = 0.0%

RR = 0.78 (95% CI 0.50 to 1.22)

Cypher in AMI: Further MI

N 744 175 320 712 310 120



Further MI

3.2%

6.9%

1.9%1.1%

5.7%

1.7%

4.6%

9.1%

1.4%

9.2%

1.9% 1.7%

0%

1%

2%

3%

4%

5%

6%

7%

8%

9%

10%

MULT

ISTRATEG

Y

STRATEGY

SESAMI

TYPHOO

N

MIS

SION

Diaz d

e la

Llera

Eve

nt R

ate

Cypher

BMS

Cypher in AMI: Further MI



STRATEGYMI 12m0.740.252.236 / 878 / 88

SESAMIMI 12m1.000.205.033 / 1603 / 160

TYPHOONMI 12m0.800.213.014 / 3555 / 357

MISSIONMI 12m0.600.251.429 / 15814 / 152

Diaz et alMI 12m1.000.0616.371 / 601 / 60

MULTISTRATEGYMI 8m 0.700.331.4812 / 37217 / 372

0.710.451.1135 / 119248 / 1189

0.10.2 0.5 1 2 5 10


Meta Analysis


RR = 0.72 (95% CI 0.47 to 1.11)

Cypher in AMI: Stent Thrombosis

N 744 175 320 712 310 120



Stent Thrombosis

2.7%

1.1% 1.3%

3.4%

1.3%

3.3%

4.0%

4.5%

0.6%

3.6%

2.0%1.7%

0%

1%

1%

2%

2%

3%

3%

4%

4%

5%

5%

Eve

nt R

ate

Cypher

BMS

def+prob

def+prob

def

protocol

protocol

def

Cypher in AMI: Stent Thrombosis

Study name Outcome Time point Statistics for each study Events / Total Odds ratio and 95% CI

Odds Lower Upper ratio limit limit Cypher BMS

STRATEGY Stent thrombosis 12m 0.24 0.03 2.23 1 / 87 4 / 88

SESAMI Stent thrombosis 12m 2.01 0.18 22.42 2 / 160 1 / 160

TYPHOON Stent thrombosis 12m 0.93 0.42 2.06 12 / 355 13 / 357

MISSION Stent thrombosis 12m 0.64 0.10 3.86 2 / 158 3 / 152

Diaz et al Stent thrombosis 12m 2.03 0.18 23.06 2 / 60 1 / 60

MULTISTRATEGY Stent thrombosis 8m 0.66 0.29 1.48 10 / 372 15 / 372

0.79 0.48 1.30 29 / 1192 37 / 1189

0.1 0.2 0.5 1 2 5 10

Favours Cypher Favours BMS


RR = 0.79 (95% CI 0.49 to 1.29)

Cypher in AMI: TVR

N 744 175 320 712 310 120


Months dual APT 3 3 12 6 12 9

% Angio follow up 0.0 90.9 51.9 24.3 82.3 0.0

TVR

3.2%

6.9%

5.0% 5.6% 5.1%

0.0%

10.2%

20.5%

13.8% 13.4% 13.2%

5.0%

0%

5%

10%

15%

20%

25%

MULT

ISTRATEG

Y

STRATEGY

SESAMI

TYPHOO

N

MIS

SION

Diaz d

e la

Llera

Eve

nt R

ate

Cypher

BMS

Cypher in AMI: TVR



STRATEGYTVR 12m0.290.110.776 / 8718 / 88

SESAMITVR 12m0.330.140.778 / 16022 / 160

TYPHOONTVR 12m0.380.220.6620 / 35548 / 357

MISSIONTVR 12m0.350.150.838 / 15820 / 152

Diaz et alTVR 12m0.140.012.690 / 603 / 60

MULTISTRATEGYTVR 8m 0.290.150.5712 / 37238 / 372

0.330.240.4654 / 1192149 / 1189

0.10.2 0.5 1 2 5 10


Meta Analysis

p (overall effect) = <0.001Heterogeneity (I2) = 0.0%

RR = 0.37 (95% CI 0.27 to 0.49)


Cardiology

Longer-term

STRATEGY 2Y

11.5%

8.0%9.2%

1.1% 1.1%0.0%

13.6%

9.1%

23.9%

4.5%

2.3%

0.0%0%

5%

10%

15%

20%

25%

30%

Death MI TVR ST def+prob ST late ST very late

Eve

nt R

ate

Cypher

BMS

STRATEGY at 2 Years

Valgimigli et al JACC 2007;50:138-45

N = 175

P = 0.66

P = 0.77

P = 0.01

P = 0.37

P = 1.00

TYPHOON @ 3 Years

Spaulding PCR 2008

N = 712

Cost-effectiveness

• Cypher AMI data into economic model that closely reproduces NICE’s results.

• Additional procedural cost of using Cypher = £471.• Costs saved by avoiding adverse events= £435.• 12m incremental cost of using Cypher = £ 36 (a)

• QALYs gained = 0.00691 (b)

• Incremental cost per QALY gained (a/b) = £5,281

(PPCI with BMS vs thrombolysis = £9,241)

Summary

• Death, MI, Stent thrombosis:

– No significant differences between Cypher & BMS.

• TVR:

– Statistically significant 63% risk reduction.

• Longer-term:

– Consistent with 12m conclusions.

• Cost-effective against NICE thresholds.


Cardiology

Back Up

Meta-analysis Key Results: All DES

Kastrati et al EHJ 2007;28:2706-13

Odds Ratio or Relative Risk?

Dead Alive

DES A B

BMS C D

RR = A/(A+B)C/(C+D)

OR = A/BC/D

my conflicts of interest are…

Documents

ami patientsdeath

dual apt33126129cypher

stent thrombosiscypher

bincremental cost

additional procedural

yearsvalgimigli et

deskastrati et

ground breaking