Intracoronary KAI-9803 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction

被引：153

作者：

Roe, Matthew T. ^{[1
]}

Hartmann, F. ^{[2
]}

Lins, J. ^{[3
]}

Batchelor, W. ^{[4
]}

Ruzyllo, W. ^{[5
]}

Kochman, J. ^{[6
]}

Armstrong, B. ^{[7
]}

Buszman, P. ^{[8
,9
]}

Leisch, F. ^{[10
]}

Baran, K. ^{[11
]}

Roubin, G. ^{[12
]}

Zenni, M. ^{[13
]}

Bilodeau, L. ^{[14
]}

Caputo, R. ^{[15
]}

Chu, A. ^{[16
]}

Lombardi, W. ^{[17
]}

Adamus, J. ^{[18
]}

Hermiller, J. ^{[20
]}

Darius, H. ^{[19
]}

Krzeminska-Pakula, M. ^{[21
]}

Saucedo, J. ^{[22
]}

Simek, S. ^{[23
]}

Zmudka, K. ^{[24
]}

Farah, T. ^{[25
]}

Hauptmann, K. ^{[26
]}

Lee, D. ^{[27
]}

Lemos, P. ^{[28
]}

Rohrbeck, S. ^{[30
]}

Moshage, W. ^{[29
]}

Strasser, R. ^{[31
]}

Albirini, A. ^{[32
]}

Anderson, E. ^{[33
]}

Bode, C. ^{[34
]}

Caramori, P. ^{[35
]}

Eaton, G. ^{[36
]}

Hoffman, S. ^{[37
]}

Huber, K. ^{[38
]}

Khoury, S. ^{[39
]}

Miller, J. ^{[40
,42
]}

Peterson, J. ^{[41
]}

Porizka, V. ^{[43
]}

Rivera, E. ^{[44
]}

Roe, M. ^{[45
]}

Schuster, P. ^{[46
]}

Stasek, J. ^{[47
]}

Zago, A. ^{[48
]}

机构：

[1] Duke Clin Res Inst, Durham, NC 27705 USA

[2] Univ Klin Schleswig Holstein Campus, Lubeck, Germany

[3] Med Ctr, Beaver, PA USA

[4] Tallahassee Mem Hosp, Tallahassee, FL USA

[5] Inst Cardiol, Warsaw, Poland

[6] SP CSK, Warsaw, Poland

[7] Wellmont Holston Valley Med Ctr, Kingsport, TN USA

[8] Gornoslaskie Centrum Medezne, Biala, Poland

[9] Oddzial Ostrych Zespolow Weincowych, Katowice, Poland

[10] Krankenhaus Landeshauptstadt Linz, Linz, Austria

[11] United Hosp, Minneapolis, MN USA

[12] Lenox Hill Hosp, New York, NY USA

[13] Jacksonville Med Ctr, Jacksonville, FL USA

[14] Montreal Heart Inst, Montreal, PQ, Canada

[15] St Josephs Hlth Ctr, Syracuse, NY USA

[16] St Francis Med Ctr, Peoria, IL USA

[17] St Joseph Hosp, Bellingham, WA USA

[18] CSK WAM, Warsaw, Poland

[19] Vivantes Krakenhaus Neukolin, Berlin, Germany

[20] Heart Ctr Indiana, Indianapolis, IN USA

[21] Szpital Bieganskiego, Lodz, Poland

[22] Univ Oklahoma, Med Ctr, Oklahoma City, OK USA

[23] VFH Prague 2, Prague, Czech Republic

[24] Zaklad Hemodynamiki CM UJ, Krakow, Poland

[25] Allegheny Gen Hosp, Pittsburgh, PA USA

[26] Krakenhaus Barmherzigen Bruder, Trier, Germany

[27] Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA

[28] INCOR, Sao Paulo, Brazil

[29] Klin Traunstein, Traustein, Germany

[30] High Point Reg Med Ctr, High Point, NC USA

[31] Tech Univ Dresden, Dresden, Germany

[32] Genesis Hlth Care Syst, Zainesville, OH USA

[33] Sequoia Hosp, Redwood City, CA USA

[34] Univ Freiburg Klinikum, Freiburg, Germany

[35] Pontificia Univ Catolica Rio de Sul, Hosp Sao Lucas, Ctr Pesquisa Cardiovasc, Porto Alegre, RS, Brazil

[36] Med Ctr Mansfield, Mansfield, PA USA

[37] Vivantes Krankenhaus Friedrichshainm, Berlin, Germany

[38] Wilhelminenspital Stadt Wien, Vienna, Austria

[39] Univ Cincinnati, Med Ctr, Cincinnati, OH USA

[40] Johns Hopkins Univ Hosp, Baltimore, MD USA

[41] Beth Israel Deaconess Med Ctr, Spokane, WA USA

[42] Inst Expt Med, Prague, Czech Republic

[43] KRC Czech, Prague, Czech Republic

[44] NW Texas Healthcare Syst, Amarillo, TX USA

[45] Duke Univ Hosp, Durham, NC USA

[46] Kardiol, Siegen, Germany

[47] FN Hradec Kralove, Hradec Kralove, Czech Republic

[48] Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil

来源：

CIRCULATION | 2008年 / 117卷 / 07期

关键词：

myocardial infarction; angioplasty; pharmacology; protein kinase inhibitors; reperfusion;

D O I：

10.1161/CIRCULATIONAHA.107.759167

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background-KAI-9803, a delta-protein kinase C inhibitor, has been shown to ameliorate injury associated with ischemia and reperfusion in animal models of acute myocardial infarction (MI). Methods and Results-Direct Inhibition of delta-Protein Kinase C Enzyme to Limit Total Infarct Size in Acute Myocardial Infarction (DELTA MI) was a "first-in-human," dose-escalation study that evaluated the safety, tolerability, and activity of KAI-9803 for patients with acute anterior ST-segment elevation MI undergoing primary percutaneous coronary intervention. Patients who presented within 6 hours of symptom onset and had an occluded left anterior descending infarct artery on angiography were randomized in a 2: 1 fashion to receive 1 of 4 doses of KAI-9803 (cohort 1, 0.05 mg; cohort 2, 0.5 mg; cohort 3, 1.25 mg; cohort 4, 5.0 mg) versus blinded concurrent placebo delivered in 2 divided doses via intracoronary injection before and after reestablishment of antegrade epicardial flow with percutaneous coronary intervention. Safety and biomarker end points were assessed. Overall, 154 patients were randomized and treated with study drug (37 in cohort 1, 38 in cohort 2, 38 in cohort 3, 41 in cohort 4). The incidence of serious adverse events was similar between patients treated with KAI-9803 versus placebo. Other safety end points, including changes in QT intervals and standard laboratory values after study drug administration, were similar between treatment groups. Although the study was not powered to demonstrate efficacy with the biomarker end points assessed, signs of drug activity with KAI-9803 were suggested by trends for consistent, nonsignificant reductions in creatine kinase-MB area under the curve and ST-recovery area under the curve values across all dosing cohorts with KAI-9803 compared with concurrent placebo, and similar trends were demonstrated for improvements in (99m)technetium sestamibi infarct size values with active study drug in cohorts 1, 2, and 3. Conclusions-KAI-9803 had an acceptable safety and tolerability profile when delivered via intracoronary injection during primary percutaneous coronary intervention for ST-segment elevation MI. Signs of potential drug activity were demonstrated with biomarker end points in this small exploratory study, indicating that further testing of KAI-9803 as an adjunctive therapy for ST-segment elevation MI is warranted.

引用

页码：886 / 896

页数：11

共 24 条

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