Comparison of 3 major randomized controlled trials measuring the utility of platelet function tests for guiding antiplatelet therapy in patients with high on-treatment platelet reactivity (clopidogrel “resistance”)
| Trial feature . | GRAVITAS74 . | ARCTIC75 . | ANTARCTIC76 . |
|---|---|---|---|
| Patient characteristics | PCI with DES: −58% stable CAD, –27% unstable angina without MI, −15% ACS | PCI with DES: 27% NSTE-ACS | Patients aged ≥75 years undergoing PCI with stenting for ACS |
| Number of patients | 2800 | 2440 | 877 |
| Platelet function test | VerifyNow P2Y12 assay HPR cutoff: ≥230 PRU | VerifyNow P2Y12 assay HPR cutoff: ≥235 PRU or ≤15% inhibition | VerifyNow P2Y12 assay HPR cutoff: ≥208 PRU, LPR cutoff: ≤85 PRU |
| Treatment type/dose in the monitoring group | Clopidogrel 600-mg loading dose, followed by 150-mg maintenance dose | Clopidogrel 600-mg loading dose plus clopidogrel 150 mg daily (−90%) or prasugrel 10 mg daily (−10%) | Prasugrel 5 mg daily (55%); prasugrel 10 mg (4%); clopidogrel 75 mg (39%) |
| Efficacy outcome (monitoring group vs conventional-treatment group) | 6-month cardiovascular death, nonfatal MI, or stent thrombosis: 2.3% vs 2.3%; HR 1.01, P = .97 | 1-year death, MI, stent thrombosis, stroke, or urgent revascularization: 34.6% vs 31.1%; HR 1.13, P = 0.10 | 1-year cardiovascular death, MI, stroke, stent thrombosis, urgent revascularization, and BARC-defined bleeding (types 2, 3, or 5): 28% vs 28%; HR 1.0, P = .98 |
| Safety outcome | Severe or moderate GUSTO bleeding: 1.4% vs 2.3%; HR = 0.59, P = .10 | Major STEEPLE bleeding:2.3% vs 3.3%; HR = 0.57, P = .12 | BARC-defined bleeding (types 2, 3, or 5): 21% vs 20%; HR 1.04, P = .77 |
| Limitations | • Low-risk patient cohort resulted in low event rate, hence underpowered to test the utility of PFM | • Low-risk patient cohort | • Uniform strategy for first 14 days: utility of PFM not tested in early period |
| • Suboptimal remedy to overcome HPR | • Suboptimal remedy to overcome H PR in majority of patients | • Therapeutic approach in the PFM group is primarily to reduce bleeding | |
| • Randomization done 12 or 24 hours after PCI, missing periprocedural events | • Underpowered for postdischarge event occurrence | • Approximately 8.7% of the PFM group did not undergo PFM on either day 14 or day 28 |
| Trial feature . | GRAVITAS74 . | ARCTIC75 . | ANTARCTIC76 . |
|---|---|---|---|
| Patient characteristics | PCI with DES: −58% stable CAD, –27% unstable angina without MI, −15% ACS | PCI with DES: 27% NSTE-ACS | Patients aged ≥75 years undergoing PCI with stenting for ACS |
| Number of patients | 2800 | 2440 | 877 |
| Platelet function test | VerifyNow P2Y12 assay HPR cutoff: ≥230 PRU | VerifyNow P2Y12 assay HPR cutoff: ≥235 PRU or ≤15% inhibition | VerifyNow P2Y12 assay HPR cutoff: ≥208 PRU, LPR cutoff: ≤85 PRU |
| Treatment type/dose in the monitoring group | Clopidogrel 600-mg loading dose, followed by 150-mg maintenance dose | Clopidogrel 600-mg loading dose plus clopidogrel 150 mg daily (−90%) or prasugrel 10 mg daily (−10%) | Prasugrel 5 mg daily (55%); prasugrel 10 mg (4%); clopidogrel 75 mg (39%) |
| Efficacy outcome (monitoring group vs conventional-treatment group) | 6-month cardiovascular death, nonfatal MI, or stent thrombosis: 2.3% vs 2.3%; HR 1.01, P = .97 | 1-year death, MI, stent thrombosis, stroke, or urgent revascularization: 34.6% vs 31.1%; HR 1.13, P = 0.10 | 1-year cardiovascular death, MI, stroke, stent thrombosis, urgent revascularization, and BARC-defined bleeding (types 2, 3, or 5): 28% vs 28%; HR 1.0, P = .98 |
| Safety outcome | Severe or moderate GUSTO bleeding: 1.4% vs 2.3%; HR = 0.59, P = .10 | Major STEEPLE bleeding:2.3% vs 3.3%; HR = 0.57, P = .12 | BARC-defined bleeding (types 2, 3, or 5): 21% vs 20%; HR 1.04, P = .77 |
| Limitations | • Low-risk patient cohort resulted in low event rate, hence underpowered to test the utility of PFM | • Low-risk patient cohort | • Uniform strategy for first 14 days: utility of PFM not tested in early period |
| • Suboptimal remedy to overcome HPR | • Suboptimal remedy to overcome H PR in majority of patients | • Therapeutic approach in the PFM group is primarily to reduce bleeding | |
| • Randomization done 12 or 24 hours after PCI, missing periprocedural events | • Underpowered for postdischarge event occurrence | • Approximately 8.7% of the PFM group did not undergo PFM on either day 14 or day 28 |
Reproduced with permission from Gurbel and Tantry.72
CAD, coronary artery disease; DES, drug-eluting stent; GUSTO, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries; HPR, high platelet reactivity to ADP; HR, hazard ratio; LPR, low platelet reactivity to ADP; MI, myocardial infarction; NSTE-ACS, non-ST-segment elevation acute coronary artery syndrome; PFM, platelet function monitoring; PRU, P2Y12 reaction units.