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.
OBJECTIVE
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 micromol/l major adverse cardiac events. A significant dose-response was also observed for the vasodilator-stimulated phosphoprotein index, a measure of P2Y(12) 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.
Montalescot
Gilles
G
Institut de Cardiologie-Pitié-Salpêtriére University Hospital, Assistence Publique Hôpiteux de Paris (APHP), Paris, France. gilles.montalescot@psl.aphp.fr
Sideris
Georges
G
Meuleman
Catherine
C
Bal-dit-Sollier
Claire
C
Lellouche
Nicolas
N
Steg
Ph Gabriel
PG
Slama
Michel
M
Milleron
Olivier
O
Collet
Jean-Philippe
JP
Henry
Patrick
P
Beygui
Farzin
F
Drouet
Ludovic
L
D000208:Acute Disease; D000244:Adenosine Diphosphate / Q000378:metabolism; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D000077144:Clopidogrel; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005260:Female; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009336:Necrosis; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D016037:Single-Blind Method; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D019210:Troponin I / Q000032:analysis
D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D019210:Troponin I; D000244:Adenosine Diphosphate; D000077144:Clopidogrel; D013988:Ticlopidine