Studies of variable platelet response to clopidogrel with clinical correlation.
| Study (year) . | Patients (no.;% female; mean age, y) . | Clopidrogel dose (mean follow-up period) . | Clopidrogel resistance assay (prevalence) . | Clinical outcome associated with clopidrogel resistance (assay results in stent thrombosis studies) . |
|---|---|---|---|---|
| Adapted from Maree and Fitzgerald, with permission.1 | ||||
| Abbreviations: PCI, percutaneous coronary intervention; ADP, adenosine diphosphate; STEMI, ST segment elevation myocardial infarction; VASP, vasodilator-stimulated phosphoprotein | ||||
| Mobley et al39 (2004) | Patients undergoing PCI (50; 20; 58) | 75 mg daily maintenance 300 mg loading clinician’s discretion 6/12 | Optical aggregometry 1 μmol/L ADP; <10% average platelet inhibition (30%) | No correlation with major adverse clinical events |
| Matetzky et al40 (2004) | Patients undergoing primary PCI for acute STEMI (60; 20; 58) | 300 mg load post PCI, then 75 mg daily x 3/12 (6 mo) | Optical aggregometry 5 μmol/L ADP (1st quartile comparison to remainder) | Recurrent cardiovascular events (40% vs 6.7%; P = .007) |
| Gurbel et al41 (2005) | Patients undergoing PCI (192; 44; 61) | 300 mg or 600 mg loading, 75 mg daily (6 mo) | Optical aggregometry 5 and 20 μmol/L ADP TEG hemostasis analyzer (upper quartile comparison to remainder) | Ischemic events (upper quartile) ADP aggregation (63 ± 12% vs 56 ± 15%, P = .02) Clot strength (74 ± 5 mm vs 65 ± 4 mm, P < .001) Time to fibrin generation (4.3 ± 1.3 min vs 5.9 ± 1.5 min, P < .001) |
| Barragan et al42 (2003) | Stent thrombosis (<30 d) vs no stent thrombosis (48 [16 cases]; 26; 67) | Clopidogrel 75 mg twice daily or ticlopidine 250 mg twice daily | Flow cytometric assay VASP phosphorylation (% platelet reactivity) | Platelet reactivity in patients with stent thrombosis vs no stent thrombosis (63.28% ± 9.56% vs 39.8 ± 10.9%; P < .0001) |
| Ajzenberg et al43 (2005) | Stent thrombosis vs no stent thrombosis (32 [10 cases]; 85; 58) | 300 mg load after PCI, then 75 mg daily × 3/12 | Coaxial cylinder shearing device Shear-induced platelet aggregation | Shear 200 S−1 (40.9 ± 12.2% vs18.2 ± 18%, P = .013) Shear 4000 S−1 (57.4 ± 16.4% vs 23.4 ± 21.2%, P = .009) |
| Gurbel et al44 (2005) | Stent thrombosis vs no stent thrombosis (120 [20 cases]; 43; 63) | 75 mg daily ± 300 mg loading | Optical aggregometry 5 and 20 μmol/L ADP P2Y12 reactivity ratio by VASP phosphorylation Flow cytometry assay of GPIIb/IIIa expression (upper quartile comparison to remainder) | 5 μmol/L ADP aggregation (49 ± 4% vs 33 ± 2%; P < .05) 20 μmol/L ADP aggregation (65 ± 3% vs 51 ± 2%; P < .001) P2Y12 reactivity ratio (69 ± 5% vs 46 ± 9%; P = .03) Mean fluorescence intensity for stimulated GPIIb/IIIa expression (138 ± 19 vs 42 ± 4; P < .001) |
| Buonamici et al45 (2007) | Stent thrombosis vs no stent thrombosis (804 [25 cases]; 25; N/A) | 600 mg loading, 75mg daily (6 mo) | Optical aggregometry 10 μmol/L ADP; aggregation ≥70% (13%) | Definite/probable stent thrombosis In responders vs non-responders 16/699 (2.3%) vs 9/105 (8.6%); P < .001 |
| Study (year) . | Patients (no.;% female; mean age, y) . | Clopidrogel dose (mean follow-up period) . | Clopidrogel resistance assay (prevalence) . | Clinical outcome associated with clopidrogel resistance (assay results in stent thrombosis studies) . |
|---|---|---|---|---|
| Adapted from Maree and Fitzgerald, with permission.1 | ||||
| Abbreviations: PCI, percutaneous coronary intervention; ADP, adenosine diphosphate; STEMI, ST segment elevation myocardial infarction; VASP, vasodilator-stimulated phosphoprotein | ||||
| Mobley et al39 (2004) | Patients undergoing PCI (50; 20; 58) | 75 mg daily maintenance 300 mg loading clinician’s discretion 6/12 | Optical aggregometry 1 μmol/L ADP; <10% average platelet inhibition (30%) | No correlation with major adverse clinical events |
| Matetzky et al40 (2004) | Patients undergoing primary PCI for acute STEMI (60; 20; 58) | 300 mg load post PCI, then 75 mg daily x 3/12 (6 mo) | Optical aggregometry 5 μmol/L ADP (1st quartile comparison to remainder) | Recurrent cardiovascular events (40% vs 6.7%; P = .007) |
| Gurbel et al41 (2005) | Patients undergoing PCI (192; 44; 61) | 300 mg or 600 mg loading, 75 mg daily (6 mo) | Optical aggregometry 5 and 20 μmol/L ADP TEG hemostasis analyzer (upper quartile comparison to remainder) | Ischemic events (upper quartile) ADP aggregation (63 ± 12% vs 56 ± 15%, P = .02) Clot strength (74 ± 5 mm vs 65 ± 4 mm, P < .001) Time to fibrin generation (4.3 ± 1.3 min vs 5.9 ± 1.5 min, P < .001) |
| Barragan et al42 (2003) | Stent thrombosis (<30 d) vs no stent thrombosis (48 [16 cases]; 26; 67) | Clopidogrel 75 mg twice daily or ticlopidine 250 mg twice daily | Flow cytometric assay VASP phosphorylation (% platelet reactivity) | Platelet reactivity in patients with stent thrombosis vs no stent thrombosis (63.28% ± 9.56% vs 39.8 ± 10.9%; P < .0001) |
| Ajzenberg et al43 (2005) | Stent thrombosis vs no stent thrombosis (32 [10 cases]; 85; 58) | 300 mg load after PCI, then 75 mg daily × 3/12 | Coaxial cylinder shearing device Shear-induced platelet aggregation | Shear 200 S−1 (40.9 ± 12.2% vs18.2 ± 18%, P = .013) Shear 4000 S−1 (57.4 ± 16.4% vs 23.4 ± 21.2%, P = .009) |
| Gurbel et al44 (2005) | Stent thrombosis vs no stent thrombosis (120 [20 cases]; 43; 63) | 75 mg daily ± 300 mg loading | Optical aggregometry 5 and 20 μmol/L ADP P2Y12 reactivity ratio by VASP phosphorylation Flow cytometry assay of GPIIb/IIIa expression (upper quartile comparison to remainder) | 5 μmol/L ADP aggregation (49 ± 4% vs 33 ± 2%; P < .05) 20 μmol/L ADP aggregation (65 ± 3% vs 51 ± 2%; P < .001) P2Y12 reactivity ratio (69 ± 5% vs 46 ± 9%; P = .03) Mean fluorescence intensity for stimulated GPIIb/IIIa expression (138 ± 19 vs 42 ± 4; P < .001) |
| Buonamici et al45 (2007) | Stent thrombosis vs no stent thrombosis (804 [25 cases]; 25; N/A) | 600 mg loading, 75mg daily (6 mo) | Optical aggregometry 10 μmol/L ADP; aggregation ≥70% (13%) | Definite/probable stent thrombosis In responders vs non-responders 16/699 (2.3%) vs 9/105 (8.6%); P < .001 |