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Randomized Controlled Trial
. 2015 Aug 28;10(8):e0135037.
doi: 10.1371/journal.pone.0135037. eCollection 2015.

High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel

Tobias Geisler  1 , Jean Booth  2 , Elli Tavlaki  1 , Athanasios Karathanos  1 , Karin Müller  1 , Michal Droppa  1 , Meinrad Gawaz  1 , Monica Yanez-Lopez  2 , Simon J Davidson  3 , Rod H Stables  4 , Winston Banya  2 , Azfar Zaman  5 , Marcus Flather  6 , Miles Dalby  7
Affiliations
Randomized Controlled Trial

High Platelet Reactivity in Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention: Randomised Controlled Trial Comparing Prasugrel and Clopidogrel

Tobias Geisler et al. PLoS One. .

Abstract

Background: Prasugrel is more effective than clopidogrel in reducing platelet aggregation in acute coronary syndromes. Data available on prasugrel reloading in clopidogrel treated patients with high residual platelet reactivity (HRPR) i.e. poor responders, is limited.

Objectives: To determine the effects of prasugrel loading on platelet function in patients on clopidogrel and high platelet reactivity undergoing percutaneous coronary intervention for acute coronary syndrome (ACS).

Patients: Patients with ACS on clopidogrel who were scheduled for PCI found to have a platelet reactivity ≥40 AUC with the Multiplate Analyzer, i.e. "poor responders" were randomised to prasugrel (60 mg loading and 10 mg maintenance dose) or clopidogrel (600 mg reloading and 150 mg maintenance dose). The primary outcome measure was proportion of patients with platelet reactivity <40 AUC 4 hours after loading with study medication, and also at one hour (secondary outcome). 44 patients were enrolled and the study was terminated early as clopidogrel use decreased sharply due to introduction of newer P2Y12 inhibitors.

Results: At 4 hours after study medication 100% of patients treated with prasugrel compared to 91% of those treated with clopidogrel had platelet reactivity <40 AUC (p = 0.49), while at 1 hour the proportions were 95% and 64% respectively (p = 0.02). Mean platelet reactivity at 4 and 1 hours after study medication in prasugrel and clopidogrel groups respectively were 12 versus 22 (p = 0.005) and 19 versus 34 (p = 0.01) respectively.

Conclusions: Routine platelet function testing identifies patients with high residual platelet reactivity ("poor responders") on clopidogrel. A strategy of prasugrel rather than clopidogrel reloading results in earlier and more sustained suppression of platelet reactivity. Future trials need to identify if this translates into clinical benefit.

Trial registration: ClinicalTrials.gov NCT01339026.

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Conflict of interest statement

Competing Interests: TG has received lecture honoraria from Eli Lilly/Daiichi Sankyo, The Medicines Company, Bayer Health Care, Bristol Myer Squibb, Pfizer, Boehringer Ingelheim, Astra Zeneca, and a restricted grant from Eli Lilly/Daiichi Sankyo. M. Dalby has received consultancy fees and research grants from Boston Scientific, Medtronic, Eli Lilly Daiichi-Sankyo, AstraZeneca, Abbot Vascular. MF has received research grants from Daiichi Sankyo/ Eli Lilly and has been on the Data and Safety Monitoring Committee for the ACCOAST trials sponsored by Eli Lilly. Research grants and honoraria for speaker meetings have been received from GSK, Novartis and Astra Zeneca. RHS reports grants from The Medicines Company and grants and personal fees from AstraZeneca. SD has received honoraria from Organon, Mitsubishi Pharma, Bayer, Werfen China, Instrumentation Laboratory. MG has received consultancy and speaker fees from Daiichi Sankyo, Eli Lilly, Sanofi and Astra Zeneca. AZ has received consultancy and speaker fees from Daiichi Sankyo, Eli Lilly, Sanofi and Astra Zeneca. All other authors declare no competing interests. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Consort flow diagram of the trial.
Fig 2
Fig 2. Diagram of inclusion and randomisation process (Abbreviations: BARC: Bleeding Academic Research Consortium; LD: Loading Dose, MACE: major adverse cardiovascular events, MEA: Multiple Electrode Aggregometry; PR: Platelet reactivity, TP: Time point, P.D.: Physician’s Discretion).
Fig 3
Fig 3. Pharmacodynamic profile showing ADP induced platelet aggregation over time according to treatment arms.
See this image and copyright information in PMC

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