A Study of Platelet Inhibition, Using a 'Point of Care' Platelet Function Test, following Primary Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction [PINPOINT-PPCI]

Abstract

Background: Rapid coronary recanalization following ST-elevation myocardial infarction (STEMI) requires effective anti-platelet and anti-thrombotic therapies. This study tested the impact of door to end of procedure ('door-to-end') time and baseline platelet activity on platelet inhibition within 24hours post-STEMI.

Methods and findings: 108 patients, treated with prasugrel and procedural bivalirudin, underwent Multiplate® platelet function testing at baseline, 0, 1, 2 and 24hours post-procedure. Major adverse cardiac events (MACE), bleeding and stent thrombosis (ST) were recorded. Baseline ADP activity was high (88.3U [71.8-109.0]), procedural time and consequently bivalirudin infusion duration were short (median door-to-end time 55minutes [40-70] and infusion duration 30minutes [20-42]). Baseline ADP was observed to influence all subsequent measurements of ADP activity, whereas door-to-end time only influenced ADP immediately post-procedure. High residual platelet reactivity (HRPR ADP>46.8U) was observed in 75% of patients immediately post-procedure and persisted in 24% of patients at 2hours. Five patients suffered in-hospital MACE (4.6%). Acute ST occurred in 4 patients, all were <120mins post-procedure and had HRPR. No significant bleeding was observed. In a post-hoc analysis, pre-procedural morphine use was associated with significantly higher ADP activity following intervention.

Conclusions: Baseline platelet function, time to STEMI treatment and opiate use all significantly influence immediate post-procedural platelet activity.

Conflict of interest statement

Competing Interests: Dr Thomas Johnson and Professor Baumbach have potential conflicts of interest; both have received speaker fees & research support from The Medicines Company. Professor Baumbach has received speaker fees & research support from Astra Zeneca & Dr Johnson has received speaker fees from Daichii-Sankyo. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. PINPOINT-PPCI study timeline.

LD–loading dose, PFA–platelet function assessment. Times displayed are medians and IQRs. *The median baseline PFA time was 2 minutes after procedure start (IQR -1 to 6). **The median residual PFA1 time was 0 minutes post procedure (IQR 0 to 2). Missing data were as follows: 1 patient was missing flow time; 5 patients were missing baseline PFA times; 4 patients were missing residual PFA1 times; 8 patients were missing residual PFA2 times; 8 patients were missing residual PFA3 times; 17 patients were missing residual PFA4 times.

Fig 2. ADP platelet reactivity profile.

Panel A—Median ADP receptor platelet activity profile in first 24 hours post-presentation with STEMI and treatment with PPCI. Red markers identify platelet response for the four acute ST patients (dotted line indicates the high residual platelet reactivity threshold of 46.8 U for ADP-test). Panel B–The profile of high residual platelet activity, in the first 24 hours, following administration of a 60 mg Prasugrel loading dose at the time of PPCI.

Fig 3. Effect of door to end of procedure time and baseline ADP platelet activity on ADP platelet function in the first 24 hours post-presentation with STEMI and treatment with PPCI.

Fig 4. Influence of pre-procedural opiate and anti-emetic treatment on platelet function in the first 24 hours post-presentation with STEMI and treatment with PPCI.

ADP: morphine effects pre-PPCI p = 0.56, end of PPCI p