ticagrelor compared with clopidogrel in patients with acute coronary syndromes the plato trial l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Ticagrelor compared with clopidogrel in patients with acute coronary syndromes – the PLATO trial PowerPoint Presentation
Download Presentation
Ticagrelor compared with clopidogrel in patients with acute coronary syndromes – the PLATO trial

Loading in 2 Seconds...

play fullscreen
1 / 21

Ticagrelor compared with clopidogrel in patients with acute coronary syndromes – the PLATO trial - PowerPoint PPT Presentation


  • 938 Views
  • Uploaded on

Ticagrelor compared with clopidogrel in patients with acute coronary syndromes – the PLATO trial. August 30, 2009 at 08.00 CET. PLATO background. In NSTE-ACS and STEMI, current guidelines recommend 12 months aspirin and clopidogrel Efficacy of clopidogrel is hampered by

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Ticagrelor compared with clopidogrel in patients with acute coronary syndromes – the PLATO trial' - Lucy


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
plato background
PLATO background
  • In NSTE-ACS and STEMI, current guidelines recommend 12 months aspirin and clopidogrel
  • Efficacy of clopidogrel is hampered by
    • slow and variable transformation to the active metabolite
    • modest and variable platelet inhibition
    • increased risk of bleeding
    • risk of stent thrombosis and MI in poor responders

PLATO = PLATelet inhibition and patient Outcomes; NSTEMI = non-ST segment elevation; STEMI = ST segment elevation; ACS = acute coronary syndromes; MI = myocardial infarction

ticagrelor azd 6140 an oral reversible p2y 12 antagonist

H

O

N

N

N

H

H

O

N

F

O

N

N

F

S

O

H

Ticagrelor (AZD 6140): an oral reversible P2Y12 antagonist

Ticagrelor is a cyclo-pentyl-triazolo-pyrimidine (CPTP)

  • Direct acting
    • Not a prodrug; does not require metabolic activation
    • Rapid onset of inhibitory effect on the P2Y12 receptor
    • Greater inhibition of platelet aggregation than clopidogrel
  • Reversibly bound
    • Degree of inhibition reflects plasma concentration
    • Faster offset of effect than clopidogrel
    • Functional recovery of all circulating platelets
plato study design
PLATO study design

NSTE-ACS (moderate-to-high risk) STEMI (if primary PCI)

Clopidogrel-treated or -naive;

randomised within 24 hours of index event

(N=18,624)

Clopidogrel

If pre-treated, no additional loading dose;

if naive, standard 300 mg loading dose,

then 75 mg qd maintenance;

(additional 300 mg allowed pre PCI)

Ticagrelor

180 mg loading dose, then

90 mg bid maintenance;

(additional 90 mg pre-PCI)

6–12-month exposure

Primary endpoint: CV death + MI + Stroke

Primary safety endpint: Total major bleeding

PCI = percutaneous coronary intervention; ASA = acetylsalicylic acid; CV = cardiovascular; TIA = transient ischaemic attack

plato a global trial
PLATO – a global trial

Argentina

Australia

Austria

Belgium

Brazil

Bulgaria

Canada

China

Czech Republic

Denmark

Finland

France

Georgia

Germany

Greece

Hong Kong

Hungary

India

Indonesia

Israel

Italy

Malaysia

Mexico

The Netherlands

Norway

Slovakia

Spain

Sweden

Switzerland

South Africa

South Korea

Taiwan

Thailand

Turkey

Ukraine

United Kingdom

United States

Philippines

PolandPortugal

Romania

Russia

Singapore

k m estimate of time to first primary efficacy event composite of cv death mi or stroke
K-M estimate of time to first primary efficacy event (composite of CV death, MI or stroke)

13

12

11.7

Clopidogrel

11

10

9.8

9

Ticagrelor

8

7

Cumulative incidence (%)

6

5

4

3

2

HR 0.84 (95% CI 0.77–0.92), p=0.0003

1

0

0

60

120

180

240

300

360

Days after randomisation

No. at risk

Ticagrelor

9,333

8,628

8,460

8,219

6,743

5,161

4,147

Clopidogrel

9,291

8,521

8,362

8,124

6,743

5,096

4,047

K-M = Kaplan-Meier; HR = hazard ratio; CI = confidence interval

primary efficacy endpoint over time composite of cv death mi or stroke
Primary efficacy endpoint over time (composite of CV death, MI or stroke)

8

8

6.60

Clopidogrel

6

6

Clopidogrel

5.43

5.28

4.77

4

Cumulative incidence (%)

Cumulative incidence (%)

4

Ticagrelor

Ticagrelor

2

2

HR 0.88 (95% CI 0.77–1.00), p=0.045

HR 0.80 (95% CI 0.70–0.91), p<0.001

0

0

31

90

150

270

330

0

10

20

30

210

Days after randomisation

Days after randomisation*

No. at risk

Ticagrelor

9,333

8,942

8,827

8,763

8,543

7,028

4,822

8,673

8,397

6,480

Clopidogrel

9,291

8,875

8,763

8,688

8,437

6,945

4,751

8,688

8,286

6,379

*Excludes patients with any primary event during the first 30 days

hierarchical testing major efficacy endpoints
Hierarchical testing major efficacy endpoints

The percentages are K-M estimates of the rate of the endpoint at 12 months.

secondary efficacy endpoints over time
Secondary efficacy endpoints over time

Cardiovascular death

Myocardial infarction

7

7

6.9

Clopidogrel

6

6

5.8

Clopidogrel

5.1

5

5

Ticagrelor

4.0

4

4

Ticagrelor

Cumulative incidence (%)

Cumulative incidence (%)

3

3

2

2

1

1

HR 0.84 (95% CI 0.75–0.95), p=0.005

HR 0.79 (95% CI 0.69–0.91), p=0.001

0

0

0

60

120

180

240

300

360

0

60

120

180

240

300

360

Days after randomisation

Days after randomisation

No. at risk

9,333

8,294

8,822

8,626

7119

5,482

4,419

Ticagrelor

9,333

8,678

8,520

8,279

6,796

5,210

4,191

9,291

8,865

8,780

8,589

7079

5,441

4,364

Clopidogrel

9,291

8,560

8,405

8,177

6,703

5,136

4,109

stent thrombosis
Stent thrombosis

(evaluated in patients with any stent during the study)

*Time-at-risk is calculated from first stent insertion in the study or date of randomisation

time to major bleeding primary safety event
Time to major bleeding – primary safety event

15

Ticagrelor

11.58

11.20

10

Clopidogrel

K-M estimated rate (% per year)

5

HR 1.04 (95% CI 0.95–1.13), p=0.434

0

0

60

120

180

240

300

360

Days from first IP dose

No. at risk

Ticagrelor

9,235

7,246

6,826

6,545

5,129

3,783

3,433

Clopidogrel

9,186

7,305

6,930

6,670

5,209

3,841

3,479

total major bleeding
Total major bleeding

13

NS

Ticagrelor

Clopidogrel

12

11.6

11.2

11

NS

10

8.9

8.9

NS

9

7.9

7.7

8

NS

7

K-M estimated rate (% per year)

5.8

5.8

6

5

4

3

2

NS

1

0.3

0.3

0

PLATO major bleeding

TIMI major bleeding

Red cell transfusion*

PLATO life-threatening/fatal bleeding

Fatal bleeding

Major bleeding and major or minor bleeding according to TIMI criteria refer to non-adjudicated events analysed with the use of a statistically programmed analysis in accordance with definition described in Wiviott SD et al. NEJM 2007;357:2001–15; *Proportion of patients (%); NS = not significant

non cabg and cabg related major bleeding
Non-CABG and CABG-related major bleeding

9

Ticagrelor

Clopidogrel

NS

7.9

8

7.4

7

NS

5.8

6

5.3

p=0.026

5

K-M estimated rate (% per year)

4.5

3.8

4

p=0.025

2.8

3

2.2

2

1

0

Non-CABGPLATO majorbleeding

Non-CABGTIMI major bleeding

CABGPLATO major bleeding

CABG TIMI major bleeding

other findings
Other findings

*p values were calculated using Fischer’s exact test

other findings laboratory parameters
Other findings – laboratory parameters

Values are mean %  SD; *p values were calculated using Fisher’s exact test

therapeutic considerations
Therapeutic considerations
  • Based on 1,000 patients admitted to hospital for ACS, using ticagrelor instead of clopidogrel for 12 months resulted in
    • 14 fewer deaths
    • 11 fewer myocardial infarctions
    • 6–8 fewer cases with stent thrombosis
    • No increase in bleedings requiring transfusion
    • 9 patients may switch to thienopyridine treatment because of reversible symptoms of dyspnoea
  • Treating 54 patients with ticagrelor instead of with clopidogrel for one year will prevent one event of CV death, MI or stroke
conclusions
Conclusions
  • Reversible, more intense P2Y12 receptor inhibition for one year with ticagrelor in comparison with clopidogrel in a broad population with ST- and non-ST-elevation ACS provides
    • Reduction in myocardial infarction and stent thrombosis
    • Reduction in cardiovascular and total mortality
    • No change in the overall risk of major bleeding

Ticagrelor is a more effective alternative than clopidogrel

for the continuous prevention of ischaemic events, stent thrombosis and death in the acute and long-term treatment of patients with ACS