Coronary Artery Disease
Conditions
Keywords
Clopidogrel, ASA, Low Response, Resistance
Brief summary
Dual antiplatelet therapy with acetylsalicylic acid (ASA, aspirin) and clopidogrel is of great importance for treatment following coronary stenting. Unfortunately the variable platelet inhibitory effectiveness compromises the antithrombotic benefit of dual antiplatelet therapy. The aim of this prospective single centre study was to reduce the low response incidence of dual antiplatelet therapy with ASA and clopidogrel based on a standardized therapy algorithm.
Detailed description
Platelet function testing using whole blood aggregometry was performed 48 hours following coronary stenting (either acute coronary syndromes or stable coronary artery disease). The antiplatelet therapy included a loading dose of 600 mg clopidogrel and 500 mg ASA, followed by 75 mg clopidogrel and 100 mg ASA once daily. Clopidogrel low-response (CLR) and/or ASA (ASA low response) were treated according to a structured therapy plan.
Interventions
DRUGOptimizing ASA and clopidogrel treatment
ASA 100 mg, ASA 300 mg, ASA 500 mg Clopidogrel 75 mg, Clopidogrel 150 mg, Ticlopidine 2x 250 mg, Prasugrel 10 mg. Intervention List: In the case of clopidogrel low-response, the maintenance dose was doubled (repeated loading dose followed by 150 mg daily), and when still ineffective ticlopidine or prasugrel, if available and not contraindicated, were used. ASA low-responders were treated by increasing the dose to 300 mg in a first step or to 500 mg ASA when the first modification was not sufficient.
Sponsors
Ruhr University of Bochum
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients with stable coronary artery disease (CAD) or acute coronary syndromes (ACS) following percutaneous coronary intervention (PCI)
Exclusion criteria
* abnormal platelet count in patients, * severe liver disorders, * current gastrointestinal disorders, * current infections, * congestive heart failure, * known bleeding disorders, * treatment with bivalirudin or glycoprotein IIb/IIIa antagonists within the last 7 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were Responders or Low-Responders of Antiplatelet Therapy as a Result of Whole Blood Aggregometry Testing (See Outcome Measure Description) | 2 years | In patients treated with aspirin and clopidogrel aggregometry was performed and depending on the results the patients were either responder or low-responder of antiplatelet therapy. The following definitions were used for clopidogrel low response (CLR: \>5 ohm when stimulated with adenosine diphosphate (ADP) 5 μM) and ASA low response (ALR: \>0 ohm;stimulated with arachidonic acid 10 μM) with the ChronoLog 590 aggregometer. In the case of low-response alternative antiplatelet therapy was modified according to the study plan (see protocol section). |
Countries
Germany
Participant flow
Recruitment details
Medical Clinic, 504 patients 2007-2010
Pre-assignment details
post coronary stenting
Participants by arm
| Arm | Count |
|---|---|
| Aspirin, Clopidogrel If the treatment with aspirin and/or clopidogrel is insufficient (platelet function testing) the dose was increased or the drug was changed (clopidogrel to ticlopidine or prasugrel) | 504 |
| Total | 504 |
Baseline characteristics
| Characteristic | Aspirin, Clopidogrel |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 210 Participants |
| Age, Categorical Between 18 and 65 years | 294 Participants |
| Age Continuous | 64.3 years STANDARD_DEVIATION 11.7 |
| Region of Enrollment Germany | 504 participants |
| Sex: Female, Male Female | 154 Participants |
| Sex: Female, Male Male | 350 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 504 |
| serious Total, serious adverse events | 0 / 504 |
Outcome results
Primary
Number of Participants Who Were Responders or Low-Responders of Antiplatelet Therapy as a Result of Whole Blood Aggregometry Testing (See Outcome Measure Description)
In patients treated with aspirin and clopidogrel aggregometry was performed and depending on the results the patients were either responder or low-responder of antiplatelet therapy. The following definitions were used for clopidogrel low response (CLR: \>5 ohm when stimulated with adenosine diphosphate (ADP) 5 μM) and ASA low response (ALR: \>0 ohm;stimulated with arachidonic acid 10 μM) with the ChronoLog 590 aggregometer. In the case of low-response alternative antiplatelet therapy was modified according to the study plan (see protocol section).
Time frame: 2 years
Population: Sample size calculation: With the assumption that the incidence of clopidogrel low response was at least 20% and ASA low response 10%. Choosing a power of 97.5% and a two-sided value of 0.05, an overall sample size was required of at least 400 patients. To compensate for a possible loss of follow-up, we aimed for inclusion of approx. 500 patients.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clopidogrel Low Response | Number of Participants Who Were Responders or Low-Responders of Antiplatelet Therapy as a Result of Whole Blood Aggregometry Testing (See Outcome Measure Description) | 155 participants |