NOVEL ANTIPLATELET

DRUGS

IN ACS

ΠΤΡΟ Ν. ΠΑΠΑΪΩΑΝΝΟΤ MD. PHD. FESC

ΕΙΔΙΚΟ ΚΑΡΔΙΟΛΟΓΟ

ΔΙΔΑΚΣΩΡ ΑΠΘ

ΑΝΑΠΛΗΡΩΣΗ ΔΙΕΤΘΤΝΣΗ ΚΑΡΔΙΟΛΟΓΙΚΗ

ΚΛΙΝΙΚΗ ΝΑΤΣΙΚΟΤ ΝΟΟΚΟΜΕΙΟΤ ΑΘΗΝΩΝ

ΠΕΡΙΕΧΟΜΕΝΑ

1. Novel antiplatelet agents-Mechanism of action

2. Ticagrelor

3. Prasugrel

4. Cangrelor

5. Elinogrel

6. Guidelines (ESC-AHA)

ΠΕΡΙΕΧΟΜΕΝΑ

1. Novel antiplatelet agents-Mechanism of action

2. Ticagrelor

3. Prasugrel

4. Cangrelor

5. Elinogrel

6. Guidelines (ESC-AHA)

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

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

K-M estimate of time to first primary efficacy

event (composite of CV death, MI or stroke)

Secondary efficacy endpoints

Stent thrombosis

Ticagrelor

(n=5,640)

Clopidogrel

(n=5,649)

HR

(95% CI) p value

Stent thrombosis, n (%)

Definite

Probable or definite

Possible, probable, definite

71 (1.3)

118 (2.1)

155 (2.8)

106 (1.9)

158 (2.8)

202 (3.6)

0.67 (0.50–0.91)

0.75 (0.59–0.95)

0.77 (0.62–0.95)

0.009

0.02

0.01

Time to major bleeding – primary

safety event

Total major bleeding

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

ΠΕΡΙΕΧΟΜΕΝΑ

1. Novel antiplatelet agents-Mechanism of action

2. Ticagrelor

3. Prasugrel

4. Cangrelor

5. Elinogrel

6. Guidelines (ESC-AHA)

TRITON TIMI-38

Study Overview

Antiplatelet therapy with aspirin and a thienopyridine is a key component in the management of acute coronary syndromes

This trial compared a novel, potent thienopyridine (prasugrel) with the standard thienopyridine (clopidogrel) in patients with acute coronary syndromes scheduled to have a coronary intervention

Prasugrel led to better cardiovascular outcomes, but at the expense of more bleeding, including fatal bleeding

A shows data for the primary efficacy end point (death from cardiovascular

causes, nonfatal myocardial infarction [MI], or nonfatal stroke) and for the key

safety end point (Thrombolysis in Myocardial Infarction [TIMI] major bleeding not

related to coronary-artery bypass grafting) (bottom) during the full follow-up

period. The hazard ratio for prasugrel, as compared with clopidogrel, for the primary

efficacy end point at 30 days was 0.77 (95% confidence interval [CI], 0.67 to 0.88;

P<0.001) and at 90 days was 0.80 (95% CI, 0.71 to 0.90; P<0.001).

TRITON TIMI 38

TRITON Diabetic Subgroup

TRITON STEMI cohort

Primary EP (CV death, MI and stroke at 15 months)

TRITON Net Clinical Benefit

Bleeding Risk Subgroups

Conclusion

In patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding

Overall mortality did not differ significantly between treatment groups

ΠΕΡΙΕΧΟΜΕΝΑ

1. Novel antiplatelet agents-Mechanism of action

2. Ticagrelor

3. Prasugrel

4. Cangrelor

5. Elinogrel

6. Guidelines (ESC-AHA)

CANGRELOR

A NOVEL INTRAVENOUS ANTIPLATELET AGENT??

•ATP analogue

•Relatively resistant to the

breakdown of endonucleotidases

•Not require metabolic activation

• Reversible competitive

antagonist

•Administered intravenously

•Th<5 min

•Rapid onset of effect

•Major use in the acute setting

CANGRELOR

CHAMPION PCI – CHAMPION PLATFORM

Negative Trials But Some Positive Angles for Cangrelor?

Both trials were discontinued prematurely due to insufficient evidence of the

clinical effectiveness of cangrelor.

There were, however, reductions in stent thrombosis and death from any

cause.

CHAMPION PHOENIX

Cangrelor

CHAMPION PHOENIXCangrelor Cuts Complications at PCI vs Clopidogrel in

CHAMPION-PHOENIX; Bleeding a Caution

CANGRELOR

February 12, 2014

Administration (FDA) advisory panel voted 7 to 2 that cangrelor (the Medicines Company, Parsippany, NJ), an intravenously administered antiplatelet agent, should not be approved for the reduction of thrombotic cardiovascular events in patients with coronary artery disease undergoing PCI.

ΠΕΡΙΕΧΟΜΕΝΑ

1. Novel antiplatelet agents-Mechanism of action

2. Ticagrelor

3. Prasugrel

4. Cangrelor

5. Elinogrel

6. Guidelines (ESC-AHA)

ELINOGREL The only reversible and competitive P2Y12 receptor antagonist

Direct-acting: no metabolic activation required

Available for intravenous and oral administration, enabling acute and chronic use

Immediate and near maximal platelet inhibition achieved with IV

Duration of action

Half-life: 12 hours

No major CYP metabolism – low potential for drug-drug interactions (including PPIs)

Balanced clearance: 50% renal; 50% hepatic (10% metabolized to pharmacologically inactive metabolite)

INNOVATE PCI-treatment schema

Clinical Endpoints

Bleeding at 24 hours

*mainly on access site

Adverse Events

* Dyspnea was generally mild, transient, and infrequently led to discontinuation

^ Most cases occurred within first 60 days and were asymptomatic; All cases resolved, even

when treatment was continued; No Hy’s Law cases.

Conclusions

IV and oral elinogrel result in greater and more rapid antiplatelet effect than clopidogrel during both the acute and chronic phase of therapy

No excess TIMI major or minor bleeding at both the 24-hr and 120-day timepoints

Dose-dependent trend of increase in less severe bleeds (Bleeding Requiring Medical Attention), mostly occurring at the vascular access site in the peri-procedural period

No significant differences in efficacy at 24 hrs or 120 days (trial not powered for efficacy)

ΠΕΡΙΕΧΟΜΕΝΑ

1. Novel antiplatelet agents-Mechanism of action

2. Ticagrelor

3. Prasugrel

4. Cangrelor

5. Elinogrel

6. Guidelines (ESC-AHA)

Conclusions

NEW ANTIPLATELET AGENTS ARE:

Effective

Rapid

Safe

And,,,In the future they could lead to decrease of the duration of DAPT in

patients with with ACS and PCI with stent implantation if combined

with new generation stents