Acute Coronary Syndromes 2015

Acute Coronary SyndromeFocus on Antiplatelet TherapyMagdy El-Masry.Prof. of Cardiology.Tanta University.

Initial assessment of patients with suspected acute coronary syndromesOther cardiac includes, among other, myocarditis, Tako-Tsubo cardiomyopathy, or tachyarrhythmias. Non-cardiac refers to thoracic diseases such as pneumonia or pneumothorax. If the initial evaluation suggests aortic dissection or pulmonary embolism, D-dimers and MDCT angiography are recommended

STEMI time delays(Time is Myocardium ) You may delay, but time will not, and lost time is never found again.Patient DelaySystem DelayFMCdoor-to-balloon time door-to-needle time

Selection of NSTE-ACS treatment strategy and timing according to initial risk stratification.

Dual Anti-Platelet Therapy (DAPT)

Pathophysiology of ACS: The Role of Platelets

Comparative pharmacokinetics of oral P2Y12 inhibitors. Time to peak platelet inhibition

Available P2Y12 blockersDAPT (ASA + clopidogrel/prasugrel/ticagrelor) is recommended after ACS (STEMI or NSTE-ACS) to reduce the risk of thrombosis

Factors linked to clopidogrel response variability.Thromb Haemost 2015; 113: 3752

PLATelet inhibition and patient Outcomes (PLATO) trial.Ticagrelor vs clopidogrel in patients with acute coronary syndromes.Acute Stroke Or Transient IsChaemic Attack TReated With Aspirin or Ticagrelor and Patient OutcomES"SOCRATES"

The PLATO Trial (Ticagrelor vs Clopidogrel)19982011

All-cause death in the ticagrelor and clopidogrel arms of the PLATO trial. Percentages are KaplanMeier estimates of the rate of the endpoint at 12 months. Mortality rates are reported in the overall population, in subgroups of patients undergoing either planned invasive or conservative strategy

Canadian Journal of Cardiology 29 (2013) 1334-1345Based on the PLATO results, the 2012 Canadian Cardiovascular Society Antiplatelet Guidelines recommend the following:

*Moderate to high-risk NSTEACS as defined in PLATO : 2 of: (1) ischemic ST changes on electrocardiogram; (2) positive blomarkers; and (3) 1 of the following: 60 years of age or greater, previous MI or CABG, CAD > 50% stenosis in 2 vessels, previous ischemic stroke, diabetes, peripheral arterial disease, or chronic renal dysfunction.

* Prasugrel should be avoided in patients with previous TIA or stroke. In patients aged 75 years and older, or body weight 60 kg, prasgurel should be used with caution and a 5 mg dose considered.

Administration of oral P2Y12 inhibitors prior to coronary angiography has long been the gold standard in patients with ACS. The aim of such a strategy was to allow stent implantation to be performed at a time when platelet activation was reduced to prevent ischemic complications and avoid early stent thrombosis.

Pretreatment would also reduce pre-PCI ischemic events by reducing thrombotic burden.

Initiating Antiplatelet Therapy In Patients With ACSMaking decisions in the ER or Cath lab when time mattersLoading ticagrelor in patients with ACS is not restricted by

Ticagrelor is a faster and more potent P2Y12inhibitor that demonstrated a significant clinical benefit over clopidogrel in ACS. It is therefore recommended as a first-line agent over clopidogrel in ACS

Caution in those with a history of COPD,asthma, HF, gout & severe renal impairment due to increased risk of dyspnea & elevated serum uric acid & creatinine.

Interplay between ticagrelor and adenosine in humans including impact on the heart, lungs, and brain (top); intestine (middle); platelets,kidneys, and liver (bottom). A1, A2A, A2B, and A3 are adenosine receptors potentially involved.Pleiotropic effects of ticagrelor

Ticagrelor inhibits cellular uptake of adenosineFormation of adenosine and its intracellular uptake and metabolism, which are reduced by ticagrelor through inhibition of ENT1(equilibrative nucleoside transporter 1)Does ticagrelor have additional mechanism(s) of action?

Potential underlying mechanisms of ticagrelors offtarget effects.

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Antiplatelet therapy post-ACS

The clinical cardiologists role

What is the optimal duration of DAPT after ACS? Duration of DAPT in Patients With ACS Treated With Medical Therapy Alone

Duration of DAPT in Patients With STEMI Treated With Fibrinolytic Therapy

Duration of DAPT in Patients With ACS Treated With PCI

Duration of DAPT in Patients With ACS Treated With CABG

Balanced Benefit/Risk Ratio

Thus, the thousand dollar question is : Where isthe sweet spot between ischaemia and bleeding?Sweet spot Ischemic RiskBleeding Risk

Shorter Duration of DAPT Trials

Duration of DAPT Trials

This study identified a sub-group of patients at high risk of recurrent ischemic events that occurred more than 12 months after an initial MI who could benefit from prolonged DAPT by aspirin and ticagrelor.

(Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin) trial

DAPT Risk Score Picks Patients for Extended Therapy'This is exactly what we need' to balance benefit and riskContinuation of DAPT beyond 1 year reduces the risk of MI and stent thrombosis, with the tradeoff of increased bleeding.

DAPT Score

Using the DAPT Score to Predict Stent Thrombosis vs. Bleeding

Master Treatment Algorithm for Duration of P2Y12 Inhibitor Therapy in Patients With CAD Treated With DAPT

Treatment Algorithm for Duration of P2Y12Inhibitor Therapy in Patient With Recent ACS (NSTE-ACS or STEMI)

2016 ACC/AHA Guideline Focused Update on Duration of DAPT in Patients With CAD (cont)