Assessment of the Best Loading Dose of Clopidogrel to Blunt Platelet Activation, Inflammation, and On-going Necrosis - ALBION


The goal of the trial was to evaluate the effect of different clopidogrel doses (300 mg, 600 mg, or 900 mg) on platelet aggregation among patients with non-ST elevation acute coronary syndromes.

Study Design

Study Design:

Patients Enrolled: 103
Mean Follow Up: 30 days
Mean Patient Age: Mean age 62 years
Female: 23

Patient Populations:

Age 18-85 years, unstable angina or non-ST elevation acute coronary syndrome with symptom onset within 48 hours, planned treatment with clopidogrel

Primary Endpoints:

Platelet aggregation

Secondary Endpoints:

Platelet activation assessed by flow cytometry

Drug/Procedures Used:

Patients were randomized prior to PCI to a clopidogrel loading dose of 300 mg (n=35), 600 mg (n=34), or 900 mg (n=34). Platelet aggregation was assessed at 30 minutes, and 1, 2, 3, 4, 5, 6 and 24 hours. All patients received a 75 mg per day maintenance dose of clopidogrel.

Concomitant Medications:

All patients were treated with aspirin and low-molecular weight heparin.

Principal Findings:

Following randomization, PCI was performed in 54%, 71%, and 53% of the 300 mg, 600 mg, and 900 mg dose groups, respectively. Percent platelet inhibition was lower in the 300 mg dose group compared with both the 600 mg group and the 900 mg group as early as 2 hours after the loading dose (p<0.05 each). VASP measurement was also lower in the 300 mg group compared with the 600 and 900 mg groups at 6 hours and through 24 hours. Inflammatory markers of hs-CRP, von Willebrand factor, and sCD40 ligand did not differ by dose group. Increased troponin levels at day 2 trended lower in the higher dose groups, but the difference was not statisitcally significant (50.0% for 300 mg, 42.9% for 600 mg, 34.6% for 900 mg). There was no difference in clinical events of death, MI, unplanned PCI, or hospitalization for repeat angina (n=4 for 300 mg, n=2 for 600 mg, n=0 for 900 mg). Likewise, total bleeding events did not differ by dose (n=11, 31.4% for 300 mg; n=10, 29.4% for 600 mg; n=14, 41.2% for 900 mg). The majority of the bleeding events were classified as mild bleeds (n=10 for 300 mg, n=10 for 600 mg, n=13 for 900 mg).


Among patients with acute coronary syndromes, treatment with higher clopidogrel doses was associated with more rapid and increased levels of platelet inhibition. The recently published ARMYDA-2 trial demonstrated a significant reduction in peri-procedural MIs and biomarker release with a 600 mg dose of clopidogrel compared with a 300 mg dose in patients undergoing coronary stenting for acute coronary syndromes, primarily stable angina. Additionally, the CLEAR PLATELETS study showed a reduction in troponin release following elective stenting with a higher 600 mg dose of clopidogrel compared with a 300 mg dose. The present study demonstrates an even higher 900 mg dose may provide additional inhibition over a 600 mg dose, although safety and clinical efficacy has not yet been assessed. The ALBION trial adds to the small but growing body of evidence suggesting a higher dose of clopidogrel may be more efficacious than the standard 300 mg dose. However, the trials conducted to date are small, and larger trials are warranted to more fully evaluate bleeding and safety events.


Montalescot G, et al. A Randomized Comparison of High Clopidogrel Loading Doses in Patients With Non–ST-Segment Elevation Acute Coronary Syndromes. J Am Coll Cardiol 2006;48:931-8.

Presented by Dr. Giles Montalescot at the EuroPCR meeting, Paris, France, May 2005.

Clinical Topics: Acute Coronary Syndromes, Stable Ischemic Heart Disease, ACS and Cardiac Biomarkers, Chronic Angina

Keywords: von Willebrand Factor, Acute Coronary Syndrome, Platelet Aggregation Inhibitors, Angina, Stable, Ticlopidine, Hospitalization, Troponin

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