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CLINICAL RESEARCH: ACUTE MYOCARDIAL INFARCTION

Effect of activated protein C on plasma plasminogen activator inhibitor activity in patients with acute myocardial infarction treated with alteplase

Comparison with unfractionated heparin

Tomohiro Sakamoto, MD^*,*, Hisao Ogawa, MD^*, Keiji Takazoe, MD^*, Michihiro Yoshimura, MD^*, Hideki Shimomura, MD, Yasushi Moriyama, MD, Hidekazu Arai, MD and Kenji Okajima, MD

^* Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
Laboratory Medicine, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
Division of Cardiology, Fukuoka Tokushukai Hospital, Kasuga, Japan

Manuscript received October 6, 2002; revised manuscript received June 18, 2003, accepted June 24, 2003.

^* Reprint requests and correspondence: Dr. Tomohiro Sakamoto, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan.
tom{at}kumamoto-u.ac.jp

OBJECTIVES: We examined whether activated protein C (APC) is an effective conjunctive therapy to thrombolysis in patients with ST-segment–elevated acute myocardial infarction (AMl).

BACKGROUND: Activated protein C possesses both systemic anticoagulant and anti-inflammatory properties. It has been also shown to enhance fibrinolysis by inhibiting plasminogen activator inhibitor (PAI) activity in vitro.

METHODS: After successful thrombolysis with alteplase, study patients were assigned to receive one of the two conjunctive therapies for 48 h intravenously: human plasma-derived APC at 0.06 mg/kg per day (APC group, n = 9) or unfractionated heparin at 100 to 400 U/kg per day, adjusted to maintain an activated partial thromboplastin time at 1.5 to 2 times of the control level (heparin group, n = 10).

RESULTS: Adverse events, including reocclusion of the recanalized infarct-related coronary artery and major or minor hemorrhagic complications, occurred more frequently in the heparin group (4 of 10 cases) than in the APC group (none of 9 cases) (p = 0.033). In the heparin group, plasma PAI activity (IU/ml, median value [range]) was increased continuously from 8 to 24 h after thrombolysis and peaked at 24 h (30.9 [11.3 to 38.5]); on the other hand, it was not increased in the APC group at 24 h after thrombolysis (11.3 [0.0 to 31.0], p < 0.01 vs. heparin group).

CONCLUSIONS: Administration of APC suppressed increasing of plasma PAI activity observed after thrombolysis in patients with AMI. The effect of APC could be more eligible, compared with heparin, as a conjunctive regimen to thrombolysis in AMI patients.

Abbreviations and Acronyms   AMI = acute myocardial infarction   anti-PC MAb = anti-human protein C monoclonal antibody   APC = activated protein C   aPTT = activated partial thromboplastin time   BSA = bovine serum albumin   CAG = coronary angiography   ECG = electrocardiogram/electrocardiographic   PAI-1 = type 1 plasminogen activator inhibitor   TBS = tris buffered saline   TNF = tumor necrosis factor   t-PA = tissue-type plasminogen activator