Major heart attacks are caused by a numerous factors, including sudden clot formation in a coronary artery leading to a blockage and heart muscle death. The clots are largely made of sticky clotting blood cells (platelets). A patient having a major heart attack is treated with emergency primary percutaneous coronary intervention (PPCI) where a wire and balloon are used to reopen the coronary artery and a stent (a slotted metal tube) is placed to keep the artery open.

Aspirin, and one of two other antiplatelet drugs (prasugrel or ticagrelor) are given prior to PPCI to prevent further clots formation. Both antiplatelet drugs are taken in tablet form and in healthy stable patients these drugs take at least 30 min to 2 hours to exert an adequate effect. Often PPCI procedures are performed well within this timescale. It is possible that having a major heart attack limits the bodies ability to absorb the drugs also.

In this study, patients with major or minor heart attacks will be given either prasugrel or ticagrelor as per licensed indications and guideline recommendations. A 15 ml blood sample will be taken at first balloon inflation to reopen the blocked artery, then after 20 minutes, 60 minutes, and 4 hours after taking the drugs. Each blood sample will be subjected to a variety of tests to determine antiplatelet drug activity.

This study will identify which of the two agents used are working effectively during PPCI, given the very short timescales involved. It will also show if patients with major heart attacks absorb the drugs less well than patients with less severe heart attacks. In the future it might be that an intravenous agent will be more valuable in the setting of PPCI.

This is a pilot study by design, which will be nonrandomized in nature. A total of 90 subjects will be included in the study distributed equally into 6 patient groups which have been carefully selected so that all patients will receive antiplatelet drugs as per current accepted NICE (National Institute for Health and aCare Excellence) guidelines and licensed indications.

In the current ethically approved protocol ver 1.4 (5/11/12) Groups 1,3 and 4 have already been recruited to and a full data set has been collected; Group 1 STEMI (ST-segment elevation myocardial infarction) prasugrel Group 3 STEMI clopidogrel Group 4 NSTEMI (Non-ST segment elevation myocardial infarction) clopidogrel

The current protocol allows for a specific group of NSTEMI patients (diabetic <75 years of age, >60 kg) treated with prasugrel to be recruited. The restrictive nature of these criteria would not allow us to make a direct comparison to STEMI patients treated with prasugrel. In light of this the eligibility criteria has been widened for NSTEMI patients to be treated with prasugrel. The proposed NSTEMI criteria is as follows:

1. Group 2: Patients with NSTEMI who are under 75 years of age and greater than 60kg in weight receive prasugrel loading (60mg) (in line with the manufacturers recommendations and licensing) after the 4 hour sample collection period those patients who are treated with percutaneous coronary intervention will receive prasugrel at a maintenance dose of 10mg daily (in line with NICE recommendations and local guidelines), those patients who do not proceed to be treated with percutaneous coronary intervention will be switched to clopidogrel 75mg daily (in line with NICE recommendations and local guidelines) on the following day.

   The investigators also propose to include recruitment of the following two groups in which ticagrelor will prescribed in accordance with NICE guidance and licenced indications:

2. Group 5: Patients admitted with STEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day)(in line with manufacturer's recommendations and licensing).

3. Group 6: Patients Admitted with NSTEMI receiving ticagrelor loading (180 mg) and then maintenance (90mg bd per day)(in line with manufacturer's recommendations and licensing) The investigators will only begin recruitment to groups 5 and 6 once patient recruitment is completed in group 2

PROCEDURE LOG:

STEMI patients will be identified following admission for PPCI. Patient consent for this group shall be a 2 stage process. Initially, a shortened patient information sheet shall be read to the patient on admission prior to PPCI as to not delay treatment. Once verbal consent has been obtained a P2Y12 inhibitor ticagrelor will be administered to the patient as per current local and national guidance. The time of loading dose will be carefully recorded and the patient transferred to the cardiac catheterization suite for PPCI. After the insertion of the radial or femoral sheath, 15 ml (approx 3 teaspoonfuls in volume) of whole blood will be drawn from this sheath at 20 minutes post dosing (or as close to this time point as practicable) and also at the first balloon inflation time. A further 15 ml will be taken at 60 minutes post dosing (or as close as is practicable). The second stage of consent will occur after PPCI when the patient has been transferred to the ward and is pain free and has been able to rest. At this stage a full patient information sheet shall be given to the patient to read and written consent will be sought. A final 15ml blood sample will be taken after 4 hours post dosing, after which the patient's participation in this study will come to an end.

NSTEMI/UA (Unstable Angina) Potential patients will be approached by a member of the research team, who will offer the patient a full written patient information sheet and obtain written consent. Following consent the patient will have been administered a P2Y12 inhibitor (prasugrel or ticagrelor). The time of loading dose will be carefully recorded. 15 ml (approx 3 teaspoonfuls in volume ) of blood will be taken at 20 minutes, 60 minutes and then 4 hours post dosing, after which the patient's participation in this study will come to an end.

For both STEMI and NSTEMI/UA groups, aspirin will already have been given in the ambulance and will be assessed at 20 minutes after P2Y12 inhibitor loading and again at 60 minutes.

Each blood sample taken will undergo a series of tests which will encompass the presence and function of the antiplatelet medication after a patient has suffered either a major or minor heart attack.

Inclusion Criteria:

1. Patients presenting with STEMI for PCI (characterized by chest discomfort, and prominent STsegment elevation)
2. Patients presenting with NSTEMI (characterized by chest discomfort, raised levels of myocardial enzymes and/or STsegment depression or prominent T wave inversion)
3. Able to give verbal consent (STEMI patients pre procedure) and/or written consent (STEMI after procedure and NSTEMI patients prior to enrolment).
4. Age>18 years of age
5. Able to take Aspirin and either prasugrel or ticagrelor.
6. Have no concurrent septic or inflammatory illness
7. Thienopyridine naive

Exclusion Criteria:

1. Be unable to provide verbal and written consent
2. Allergic to aspirin or any of the P2Y12 antagonists in the trial
3. Have preexisting cardiogenic shock
4. Have a concurrent septic or inflammatory disease e.g. rheumatoid arthritis, lupus, pneumonia.
5. Already taking a P2Y12 inhibitor
6. Known bleeding diathesis
7. Patients under 75 years of age or under 60 kg or those who have had a previous stroke/transient ischaemic attack, will not be eligible for prasugrel but rather ticagrelor.
8. Patients with a history of intracranial haemorrhage will not receive prasugrel or ticagrelor but rather will receive treatment with clopidogrel.

4 hours