Обзор американских кардиологических журналов за неделю (ссылки)

[Chevychelov]

Trial Summary
INNOVATE PCI Title: Intravenous and Oral Elinogrel, a Selective and Reversible P2Y12 Receptor Inhibitor in Patients Undergoing Nonurgent PCI
Trial Sponsor: Portola Pharmaceuticals
Year Presented: 2010
Topic(s): Interventional Cardiology, General Cardiology
Summary Posted: 08/30/2010
Writer: Anthony A. Bavry, M.D., M.P.H., F.A.C.C.
Author Disclosure: NOTHING TO DISCLOSE
Reviewer: Christopher P. Cannon, M.D., F.A.C.C.
Reviewer Disclosure: CONSULTING FEES/HONORARIA: Novartis, Alnylam, BMS EQUITY INTERESTS: Automedics Medical Systems RESEARCH/RESEARCH GRANTS: Merck, Accumetrics , Sanofi-aventis/Bristol-Myers Squibb Parnership, AstraZeneca Takeda, Glaxo Smith Kline, Intekrin OTHER FINANCIAL BENEFIT: Pfizer

Description:
The goal of the trial was to evaluate treatment with the intravenous (IV) and oral P2Y12 receptor inhibitor PRT060128 (elinogrel) compared with clopidogrel during nonurgent percutaneous coronary intervention (PCI). Elinogrel is a direct acting agent, which competitively binds to the P2Y12 receptor.
Hypothesis:

This is a phase II dose-finding study for elinogrel.
Drugs/Procedures Used:
Patients undergoing nonurgent PCI were randomized to one of four groups prior to PCI: 1) elinogrel 80 mg IV, then 50 mg oral twice daily; 2) elinogrel 80 mg IV, then 100 mg oral twice daily; 3) elinogrel 80 mg IV, then 150 mg oral twice daily; or 4) clopidogrel 300-600 mg, then 75 mg daily.

After the trial began, the Data Safety and Monitoring Board recommended increasing the IV dose of elinogrel from 80 mg to 120 mg and discontinuing the 50 mg twice daily arm. The chronic phase was also extended from 2 to 4 months.
Principal Findings:
Overall, 616 patients were randomized. In the pooled elinogrel 150 mg group, the median age was 61 years, 22% were women, body mass index was 29 kg/m2, 40% were diabetics, 45% were on chronic clopidogrel therapy, and femoral access was used in 75%.

Inhibition of platelet aggregation was greater with elinogrel versus clopidogrel.

There were no TIMI major bleeds in any group. There was a numerical increase in access bleeds requiring medical attention with higher doses of elinogrel compared with clopidogrel. Ischemic outcomes are similar across the study groups. Death, MI, stroke, or revascularization occurred in approximately 2.8% of the elinogrel 150 mg group, 4% of the elinogrel 100 mg group, and 1.5% of the clopidogrel group (p = NS).

Any serious adverse event occurred in 12.6% of the elinogrel 150 mg group, 14.9% of the elinogrel 100 mg group, and 11.1% of the clopidogrel group. Dyspnea occurred in 12.1%, 15.4%, and 4.3%, whereas alanine aminotransferase (ALT)/aspartate aminotransferase (AST) >3 x upper limit of normal occurred in 4.8%, 4.0%, and 1.0%, respectively.
Interpretation:

Among patients undergoing nonurgent PCI, elinogrel resulted in greater antiplatelet effect compared with clopidogrel. There were no TIMI major bleeds in any group, although access site bleeds that required medical attention were numerically higher with increasing doses of elinogrel. Similar to ticagrelor, dyspnea was more common with the study drug. Certain properties of elinogrel are attractive such as the IV and oral formulations, which can be used for acute and chronic settings; however, the increase in liver enzymes will need to be carefully monitored during future phase III studies.
Conditions:
Coronary heart disease
Coronary heart disease / Angina pectoris
Coronary heart disease / Angina pectoris / Stable
Prevention
Therapies:
Antiplatelet agent
Medical
Study Design:
Parallel. Randomized.
Primary Endpoints:
TIMI major/minor bleeding
Bleeding requiring medical attention
Clinically relevant major/minor/nuisance bleeding
Secondary Endpoints:
Troponin elevation >2 x upper limit of normal at 24 hours
Death, MI, stroke, revascularization, bailout glycoprotein IIb/IIIa inhibitor use, or stent thrombosis at 24 hours
Death, MI, stroke, or revascularization at 4 months
Death, MI, stroke, revascularization, or stent thrombosis at 4 months
Patient Population:
Patients undergoing nonurgent PCI of at least one coronary lesion

Number of enrollees: 616
Duration of follow-up: 4 months
Mean patient age: median 61 years
Percentage female: 22%
Exclusions:
Anemia/thrombocytopenia
Recent trauma/bleeding
Stroke or transient ischemic attack within the last 5 years
Clopidogrel load within the last 7 days
Use of thrombolytics, anticoagulates, or fondaparinux
Age >75 years
Weight <55 kg
Creatinine clearance <45 cc/min
Allergy to study medication
References:

Presented by Dr. Sunil Rao at the European Society of Cardiology Congress, Stockholm, Sweden, August 2010.