Antiplatelet Therapy After Cardiac Arrest

Phase 4

Completed

Conditions: Postresuscitation Syndrome
Cardiac Arrest
Myocardial Infarction (ST-Elevation Myocardial Infarction and Non-ST-Elevation Myocardial Infarction)

Brief Summary: There is growing evidence that standard dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel is not as effective in the setting of therapeutic hypothermia after cardiac arrest as in normothermic patients. The reasons for this are probably slower gastrointestinal motility, absorption and liver metabolism required for clopidogrel to take action. Since ticagrelor has faster intestinal absorption and no need for liver metabolism we expect its effect to be good even in patients with therapeutic hypothermia after cardiac arrest. Patients treated with therapeutic hypothermia after cardiac arrest and percutaneous coronary intervention will be randomised into two groups. One will be treated with ASA and clopidogrel and the other with ASA and ticagrelor. Blood samples will be collected before and 2, 4, 12, 22 and 48 hours after P2Y12 inhibitor administration. Platelet function will be measured by VerifyNow P2Y12 assay and by Multiplate ADPTest. Differences between the groups will be analysed.

Hypothesis: Antiplatelet therapy with ticagrelor is more effective than therapy with clopidogrel in the comatose survivors of cardiac arrest treated with therapeutic hypothermia and percutaneous coronary intervention (PCI).

Recruitment & Eligibility

Inclusion Criteria

Female and male over 18 years old
Unconscious survivors of cardiac arrest treated with therapeutic hypothermia
Acute coronary syndrome (NSTEMI or STEMI) as a reason of cardiac arrest
PCI with stent implantation
Provision of informed consent prior to any study specific procedures is impossible because subjects are unconscious at the moment of inclusion

Exclusion Criteria

Use of any P2Y12 inhibitors in last 10 days
Use of prasugrel before and 48 hours after loading dose of P2Y12 inhibitor
Use of eptifibatide before and 48 hours after loading dose of P2Y12 inhibitor
Thrombocytopenia (<50*109/L)
Allergic reaction to acetylsalicylic acid, clopidogrel or ticagrelor
Ticagrelor contraindications: previous intracranial bleeding, active pathological bleeding, moderate to severe hepatic impairment, heart rate < 40/min at presentation
Suspected or confirmed pregnancy
Use of bivalirudin before and 48 hours after loading dose of P2Y12 inhibitor

Arm && Interventions

Group	Intervention	Description
Clopidogrel	Clopidogrel	These patients will be treated with clopidogrel 600 mg loading and than 75 mg/24 h.
Ticagrelor	Ticagrelor	These patients will be treated with ticagrelor 180 mg loading and than 90 mg/12 h.

Primary Outcome Measures

Name	Time	Method
VerifyNow P2Y12Test - Platelet Reactivity	12 h after P2Y12 inhibitor loading	Platelet reactivity reflects P2Y12 inhibitor effect. Higher values mean normal platelet reactivity due to low P2Y12 inhibition response, while lower values mean decreased platelet reactivity due to the effect of a P2Y12 inhibitor. High on-treatment platelet reactivity was defined as \>208 PRU.

Secondary Outcome Measures

Name	Time	Method
Multiplate ADP Test	12 hours after P2Y12 inhibitor loading	Platelet activation by adenosine diphosphate (ADP) expressed in arbitrary aggregation units (U). P2Y12 inhibitors block ADP receptors and decrease platelet activation by ADP. Higher values mean less effect of P2Y12 inhibitors, lower values mean more effect of P2Y12 inhibitors on platelets. High on-treatment platelet reactivity was defined as \>46 U.
VerifyNow P2Y12Test - % Inhibition	12 hours after P2Y12 inhibitor loading	% inhibition reflects P2Y12 inhibitor effect regarding basal platelet reactivity (defined as: (1- (platelet reactivity/basal platelet reactivity)) x 100). Higher values mean better P2Y12 inhibition response. High on-treatment platelet reactivity was defined as \<11% inhibition.