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CLINICAL RESEARCH: ACUTE CORONARY SYNDROME

A Randomized Comparison of High Clopidogrel Loading Doses in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes

The ALBION (Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation and Ongoing Necrosis) Trial

Gilles Montalescot, MD, PhD^_*,1,_*, Georges Sideris, MD, Catherine Meuleman, MD, Claire Bal-dit-Sollier, MB^,1, Nicolas Lellouche, MD^||, Ph. Gabriel Steg, MD^¶,1, Michel Slama, MD^#, Olivier Milleron, MD^_**, Jean-Philippe Collet, MD, PhD^_*, Patrick Henry, MD, Farzin Beygui, MD, PhD^_*, Ludovic Drouet, MD, PhD^,1 for the ALBION Trial Investigators

^_* Institut de Cardiologie–Pitié-Salpêtriére University Hospital, Assistence Publique Hôpiteux de Paris (APHP), Paris, France.
Service de Cardiologie–Lariboisiére University Hospital, APHP, Paris, France.
Service de Cardiologie–Saint-Antoine University Hospital, APHP, Paris, France.
Laboratoire d’Hémostase–Lariboisière University Hospital, APHP, Paris, France.
^|| Service de Cardiologie–Henri-Mondor University Hospital, APHP, Paris, France.
^¶ Service de Cardiologie–Hôpital Bichat-Claude Bernard, APHP, Paris, France.
^# Service de Cardiologie–Antoine Béclère University Hospital, APHP, Paris, France.
^_** Service de Cardiologie–Ambroise Paré University Hospital, APHP, Paris, France.

Manuscript received September 26, 2005; revised manuscript received April 20, 2006, accepted April 25, 2006.

^_* Reprint requests and correspondence to: Dr. Gilles Montalescot, Institut de Cardiologie, Bureau 2-236, Pitié-Salpêtrière Hospital, 47 Boulevard de l’Hôpital, 75013 Paris, France. (Email: gilles.montalescot{at}psl.aphp.fr).

OBJECTIVES: We sought to compare the antiplatelet effects of three clopidogrel loading doses (LDs).

BACKGROUND: Administration of a 300-mg clopidogrel LD is beneficial in situations requiring rapid platelet inhibition. Whether higher LDs can provide further benefits remains unknown.

METHODS: Patients (n = 103) with non–ST-segment elevation acute coronary syndromes were randomized to receive a 300-mg, 600-mg, or 900-mg clopidogrel LD, given on top of other standard therapy (including acetylsalicylic acid). The main outcome measure was inhibition of adenosine diphosphate-induced inhibition of platelet aggregation (IPA); inhibition of platelet activation, inflammatory markers, troponin I release, and major adverse cardiac events also were evaluated; all measures were blindly evaluated.

RESULTS: Compared with the 300-mg LD, greater doses were associated with significantly greater platelet inhibition, with dose-effect relationships observed for onset of action, maximal plateau, 24-h areas under the curves of IPA, and rates of low IPA (<10% at 6 h), using 20 µmol/l major adverse cardiac events. A significant dose-response was also observed for the vasodilator-stimulated phosphoprotein index, a measure of P2Y₁₂ receptor inhibition. Similar but nonsignificant trends were observed for troponin release and major adverse cardiac events. Bleeding rates were similar in each group.

CONCLUSIONS: In low-to-moderate risk patients with non–ST-elevation acute coronary syndromes, clopidogrel LDs >300 mg provide a faster onset of action, a higher IPA plateau, and greater reductions in platelet activation during the first 24 h. A 900-mg LD may induce a greater antiplatelet effect than 600 mg, when compared with the standard 300-mg regimen. These findings require further clinical confirmation.

Abbreviations and Acronyms   ADP = adenosine diphosphate   ASA = acetylsalicylic acid   AUC = area under the inhibition of platelet aggregation curve   GP = glycoprotein   IPA = inhibition of platelet aggregation   LD = loading dose   LMWH = low molecular weight heparin   MACE = major adverse cardiac events   MFI = median fluorescence intensity   NSTE-ACS = non–ST-segment elevation acute coronary syndrome   PA = platelet aggregation   PAI = plasminogen activator inhibitor   PCI = percutaneous coronary intervention   PGE1 = prostaglandin E1   sCD40L = soluble CD40 ligand   VASP = vasodilator-stimulated phosphoprotein   vWF Ag = von Willebrand factor antigen

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