Abstract | OBJECTIVES: The aim of this randomized placebo-controlled trial was to determine if withdrawing clopidogrel therapy leads to increased platelet activity compared with pre-treatment values in patients with stable coronary artery or peripheral arterial disease. BACKGROUND: Reports of increased cardiovascular events after planned cessation of clopidogrel therapy have raised concerns over the possible existence of a rebound in platelet activity. METHODS: In all, 171 patients receiving established aspirin therapy were randomly assigned to placebo or clopidogrel (75 mg daily) for 28 days. Blood samples were taken at pre-treatment baseline, on treatment just before discontinuation of study drug, and on days 7, 14, and 28 after discontinuation. The primary outcome measure was adenosine diphosphate ( ADP)-stimulated platelet fibrinogen binding. Six secondary outcomes were assessed: ADP-stimulated platelet P-selectin, unstimulated platelet fibrinogen binding, and light transmission aggregometry with ADP 5 and 10 μmol/l recorded at maximum and at 6 min. RESULTS: The ADP-stimulated platelet fibrinogen binding, P-selectin expression, and platelet aggregation were lower on treatment with clopidogrel compared with baseline (p < 0.0001), but returned to baseline levels by 7 days after discontinuation. Mixed model analyses excluding the on-treatment timepoint showed no overall differences between the clopidogrel and placebo groups (p > 0.05). Furthermore, there was no evidence of an interaction between platelet inhibition over time and treatment allocation. CONCLUSIONS:
|
Authors | Isobel Ford, Neil W Scott, Vera Herd, Louise R Mitchell, David J P Williams, Julie Brittenden |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 63
Issue 3
Pg. 233-9
(Jan 28 2014)
ISSN: 1558-3597 [Electronic] United States |
PMID | 24211510
(Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- P-Selectin
- Platelet Aggregation Inhibitors
- Clopidogrel
- Ticlopidine
|
Topics |
- Adult
- Aged
- Aged, 80 and over
- Blood Platelets
(drug effects, metabolism)
- Cardiovascular Diseases
(blood, drug therapy)
- Clopidogrel
- Dose-Response Relationship, Drug
- Female
- Follow-Up Studies
- Humans
- Male
- Middle Aged
- P-Selectin
(blood)
- Platelet Aggregation
(drug effects)
- Platelet Aggregation Inhibitors
(administration & dosage)
- Platelet Function Tests
- Prospective Studies
- Ticlopidine
(administration & dosage, analogs & derivatives)
- Treatment Outcome
- Withholding Treatment
|