A randomised controlled trial of platelet activity before and after cessation of clopidogrel therapy in patients with stable cardiovascular disease

Isobel Ford, Neil W. Scott, Vera Herd, Louise R. Mitchell, David J.P. Williams, Julie Brittenden

Research output: Contribution to journalArticle

12 Citations (Scopus)

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
This trial found no evidence for rebound of platelet activity to above baseline after stopping clopidogrel in patients with stable coronary artery disease or peripheral arterial disease. (Is Cessation of Clopidogrel Therapy Associated With Rebound of Platelet Activity in Stable Vascular Disease Patients?; ISRCTN77887299/77887299)
Original languageEnglish
Pages (from-to)233-239
Number of pages7
JournalJournal of the American College of Cardiology
Volume63
Issue number3
Early online date6 Nov 2013
DOIs
Publication statusPublished - 28 Jan 2014

Fingerprint

clopidogrel
Cardiovascular Diseases
Blood Platelets
Randomized Controlled Trials
Adenosine Diphosphate
Fibrinogen
P-Selectin
Therapeutics
Peripheral Arterial Disease
Placebos

Keywords

  • clopidogrel
  • platelets
  • rebound

Cite this

A randomised controlled trial of platelet activity before and after cessation of clopidogrel therapy in patients with stable cardiovascular disease. / Ford, Isobel; Scott, Neil W.; Herd, Vera; Mitchell, Louise R.; Williams, David J.P.; Brittenden, Julie.

In: Journal of the American College of Cardiology, Vol. 63, No. 3, 28.01.2014, p. 233-239.

Research output: Contribution to journalArticle

@article{85cf102048f644eab2c8cf718583145f,
title = "A randomised controlled trial of platelet activity before and after cessation of clopidogrel therapy in patients with stable cardiovascular disease",
abstract = "ObjectivesThe 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.BackgroundReports of increased cardiovascular events after planned cessation of clopidogrel therapy have raised concerns over the possible existence of a rebound in platelet activity.MethodsIn 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.ResultsThe 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.ConclusionsThis trial found no evidence for rebound of platelet activity to above baseline after stopping clopidogrel in patients with stable coronary artery disease or peripheral arterial disease. (Is Cessation of Clopidogrel Therapy Associated With Rebound of Platelet Activity in Stable Vascular Disease Patients?; ISRCTN77887299/77887299)",
keywords = "clopidogrel, platelets, rebound",
author = "Isobel Ford and Scott, {Neil W.} and Vera Herd and Mitchell, {Louise R.} and Williams, {David J.P.} and Julie Brittenden",
note = "Acknowledgments The expertise of the pharmacists of Tayside Pharmaceuticals, Ninewells Hospital, Dundee, Scotland, and support from the School of Medicine and Dentistry, University of Aberdeen, and NHS Grampian Research and Development are gratefully acknowledged. Ms. K. J. Wilde, University of Aberdeen, provided expert data management.",
year = "2014",
month = "1",
day = "28",
doi = "10.1016/j.jacc.2013.10.018",
language = "English",
volume = "63",
pages = "233--239",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "3",

}

TY - JOUR

T1 - A randomised controlled trial of platelet activity before and after cessation of clopidogrel therapy in patients with stable cardiovascular disease

AU - Ford, Isobel

AU - Scott, Neil W.

AU - Herd, Vera

AU - Mitchell, Louise R.

AU - Williams, David J.P.

AU - Brittenden, Julie

N1 - Acknowledgments The expertise of the pharmacists of Tayside Pharmaceuticals, Ninewells Hospital, Dundee, Scotland, and support from the School of Medicine and Dentistry, University of Aberdeen, and NHS Grampian Research and Development are gratefully acknowledged. Ms. K. J. Wilde, University of Aberdeen, provided expert data management.

PY - 2014/1/28

Y1 - 2014/1/28

N2 - ObjectivesThe 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.BackgroundReports of increased cardiovascular events after planned cessation of clopidogrel therapy have raised concerns over the possible existence of a rebound in platelet activity.MethodsIn 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.ResultsThe 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.ConclusionsThis trial found no evidence for rebound of platelet activity to above baseline after stopping clopidogrel in patients with stable coronary artery disease or peripheral arterial disease. (Is Cessation of Clopidogrel Therapy Associated With Rebound of Platelet Activity in Stable Vascular Disease Patients?; ISRCTN77887299/77887299)

AB - ObjectivesThe 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.BackgroundReports of increased cardiovascular events after planned cessation of clopidogrel therapy have raised concerns over the possible existence of a rebound in platelet activity.MethodsIn 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.ResultsThe 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.ConclusionsThis trial found no evidence for rebound of platelet activity to above baseline after stopping clopidogrel in patients with stable coronary artery disease or peripheral arterial disease. (Is Cessation of Clopidogrel Therapy Associated With Rebound of Platelet Activity in Stable Vascular Disease Patients?; ISRCTN77887299/77887299)

KW - clopidogrel

KW - platelets

KW - rebound

U2 - 10.1016/j.jacc.2013.10.018

DO - 10.1016/j.jacc.2013.10.018

M3 - Article

VL - 63

SP - 233

EP - 239

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 3

ER -