Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Trial Summary GRAVITAS
Title: Gauging Responsiveness with A VerifyNow Assay—Impact on Thrombosis And Safety
Trial Sponsor: Accumetrics
Year Presented: 2010
Topic(s): General Cardiology, Interventional Cardiology, Prevention/Vascular
Summary Posted: 11/16/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Deepak L. Bhatt, M.D., M.P.H., F.A.C.C.
Reviewer Disclosure: RESEARCH/RESEARCH GRANTS: Astra Zeneca(SIGNIFICANT), Eisai(SIGNIFICANT), Sanofi Aventis(SIGNIFICANT), The Medicines Company(SIGNIFICANT), Ethicon(SIGNIFICANT), Bristol Myers Squibb(SIGNIFICANT), Heartscape(SIGNIFICANT), Cogentus(NONE), PLx Pharma(NONE), Takeda(NONE)

Description:

The goal of the trial was to evaluate treatment with an additional loading dose and higher maintenance dose of clopidogrel compared with no additional loading dose and standard maintenance dose of clopidogrel among patients with high residual platelet activity after percutaneous coronary intervention (PCI).
Hypothesis:

An additional loading dose and higher maintenance dose of clopidogrel will be more effective at preventing cardiovascular outcomes.
Drugs/Procedures Used:
Patients with high residual platelet activity after PCI with drug-eluting stents were randomized to clopidogrel 600 mg post-PCI, then 150 mg daily (n = 1,109) versus no additional loading dose and 75 mg daily (n = 1,105).

Platelet activity was assessed by the VerifyNow P2Y12 test 12-24 hours after PCI. High residual platelet activity was defined as a platelet reactivity unit ≥230.
Concomitant Medications:

All patients received aspirin 81-162 mg daily.
Principal Findings:
Overall, 2,214 patients were randomized. In the high-clopidogrel dose group, the mean age was 64 years, 35% were women, 44% had diabetes, 60% had stable angina, and total stent length was 30 mm. At 30 days, persistently high platelet reactivity was present in 40% of the high-clopidogrel dose group versus 62% of the standard-dose group (p < 0.001).

The primary outcome of cardiovascular death, myocardial infarction, or stent thrombosis occurred in 2.3% of the high-clopidogrel dose group versus 2.3% of the standard-dose group (p = 0.98). The primary outcome was compared among patients with high platelet reactivity treated with standard-dose clopidogrel versus screened/nonrandomized patients who had low platelet reactivity: 2.3% versus 1.4% (p = 0.20).

GUSTO moderate or severe bleeding occurred in 1.4% versus 2.3% (p = 0.10), whereas any GUSTO bleeding occurred in 12.1% versus 10.3% (p = 0.18), respectively.
Interpretation:
Among patients with high residual platelet reactivity after PCI with drug-eluting stents, treatment with high-dose clopidogrel was not beneficial. High-dose clopidogrel for 6 months did not reduce the primary ischemic outcome; however, GUSTO moderate or severe bleeding was not increased. Routine testing of platelet reactivity after PCI is not warranted. It is unknown if a more potent antiplatelet agent would have achieved different results.
Study Design:
Blinded. Parallel. Randomized. Placebo Controlled.
Primary Endpoints:
Composite of cardiovascular death, myocardial infarction, or stent thrombosis at 6 months
Secondary Endpoints:
GUSTO moderate or severe bleeding
Patient Population:
Patients undergoing PCI with a drug-eluting stent for stable or unstable coronary syndromes

Number of screened applicants: 5,429
Number of enrollees: 2,214
Duration of follow-up: 6 months
Mean patient age: 64 years
Percentage female: 35%
Exclusions:
Bleeding event prior to platelet function testing
Recent use of a glycoprotein IIb/IIIa inhibitor
References:
Presented by Dr. Matthew Price at the American Heart Association Scientific Sessions, Chicago, IL, November 16, 2010.