Point of care platelet activity measurement in primary PCI [PINPOINT-PPCI]: a protocol paper.
BACKGROUND
Optimal treatment of acute ST-elevation myocardial infarction (STEMI) involves rapid diagnosis, and transfer to a cardiac centre capable of percutaneous coronary intervention (PCI) for immediate mechanical revascularisation. Successful treatment requires rapid return of perfusion to the myocardium achieved by thromboaspiration, passivation of the culprit lesion with stent scaffolding and systemic inhibition of thrombosis and platelet activation. A delicate balance exists between thrombosis and bleeding and consequently anti-thrombotic and antiplatelet treatment regimens continue to evolve. The desire to achieve reperfusion as soon as possible, in the setting of high platelet reactivity, requires potent and fast-acting anti-thrombotic/anti-platelet therapies. The associated bleeding risk may be minimised by use of short-acting anti-thrombotic intravenous agents. However, effective oral platelet inhibition is required to prevent recurrent thrombosis. The interaction between baseline platelet reactivity, timing of revascularisation and effective inhibition of thrombosis is yet to be formally investigated.


METHODS
We present a protocol for a prospective observational study in patients presenting with acute STEMI treated with primary PCI (PPCI) and receiving bolus/infusion bivalirudin and prasugrel therapy. The objective of this study is to describe variation in platelet reactivity, as measured by the multiplate platelet function analyser, at presentation, the end of the PPCI procedure and 1, 2, & 24 hours post-procedure. We intend to assess the prevalence of high residual platelet reactivity within 24 hours of PPCI in acute STEMI patients receiving prasugrel and bivalirudin. Additionally, we will investigate the association between high platelet reactivity before and after PPCI and the door-to-procedure completion time.This is a single centre study with a target sample size of 108 participants.


CONCLUSIONS
The baseline platelet reactivity on presentation with a STEMI may impact on the effect of acute anti-thrombotic and anti-platelet therapy and expose patients to a heightened risk of bleeding or ongoing thrombosis. This study will define the baseline variation in platelet reactivity in a population of patients experiencing acute STEMI and assess the pharmacodynamic response to combined treatment with bivalirudin and prasugrel. The data obtained from this trial will be hypothesis generating for future trials testing alternative pharmacotherapies in the acute phase of treatment for STEMI.


BACKGROUND
This study has approval from Wiltshire research ethics committee (10/H0106/87) and is registered with current controlled trials (http://www.controlled-trials.com/ISRCTN82257414).
Bristol Heart Institute, Bristol Royal Infirmary, Upper Maudlin Street, Bristol BS2 8HW, UK. Tom.Johnson@uhbristol.nhs.uk.
Thomas W
TW
Johnson
Debbie
D
Marsden
Andrew
A
Mumford
Katie
K
Pike
Stuart
S
Mundell
Mark
M
Butler
Julian W
JW
Strange
Ruth
R
Bowles
Chris
C
Rogers
Andreas
A
Baumbach
Barnaby C
BC
Reeves
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002985:Clinical Protocols; D003328:Coronary Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D016903:Drug Monitoring / Q000379:methods*; D004359:Drug Therapy, Combination; D004739:England; D006470:Hemorrhage / Q000139:chemically induced; D006629:Hirudins / Q000009:adverse effects; D006801:Humans; D009203:Myocardial Infarction / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D010446:Peptide Fragments / Q000009:adverse effects / Q000627:therapeutic use*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D010979:Platelet Function Tests; D019095:Point-of-Care Systems; D000068799:Prasugrel Hydrochloride; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012107:Research Design; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D006629:Hirudins; D010446:Peptide Fragments; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D013876:Thiophenes; D000068799:Prasugrel Hydrochloride; C074619:bivalirudin