Recombinant hirudin in patients with chronic, stable coronary artery disease. Safety, half-life, and effect on coagulation parameters.
نویسندگان
چکیده
BACKGROUND Because the specific antithrombin hirudin prevents platelet-rich arterial thrombus and accelerates thrombolysis in a variety of animal models, it has promise as antithrombotic therapy. We therefore studied the half-life, effect on anticoagulant parameters, and safety of hirudin in patients with coronary artery disease. METHODS AND RESULTS Thirty-eight men and 1 woman (age [mean +/- SD], 60.4 +/- 6.9 years) with angiographic coronary disease were allocated in a single-blind ascending dosage study to a 6-hour i.v. infusion of recombinant hirudin (CGP 39,393) or matching placebo. The median terminal half-life for hirudin, measured by ELISA, was 2.7, 2.3, 2.9, 3.1, and 2.0 hours for the 0.02, 0.05, 0.1, 0.2, and 0.3 mg.kg-1 x h-1 groups, respectively. Activated partial thromboplastin times (aPTT) at 3, 4, and 6 hours were averaged into a plateau value. The aPTT plateau-to-baseline ratios were 1.5 +/- 0.1, 2.0 +/- 0.1, 2.3 +/- 0.1, 2.7 +/- 0.1, and 2.9 +/- 0.1, respectively, with hirudin infused at 0.02, 0.05, 0.1, 0.2, and 0.3 mg.kg-1 x h-1. From 62% to 77% of the aPTT plateau value was seen within 30 minutes of starting the infusions and was directly related to dose. The aPTT-to-baseline ratios correlated well with plasma hirudin levels (r = .88), whereas poor correlation and sensitivity were observed between plasma hirudin levels and activated coagulation time (ACT)-to-baseline ratios (r = .44). Plasma levels of hirudin and ACT in seconds correlated overall well (r = .80), but considerable overlap occurred between baseline ACT and ACT at plasma hirudin concentrations < 1000 ng/mL. Prothrombin times were significantly prolonged only at a dosage of > or = 0.05 mg.kg-1 x h-1 and were 11.8 +/- 0.5 (INR = 1.0), 12.3 +/- 0.7 (INR = 1.1), 13.3 +/- 1.2 (INR = 1.4), 14.2 +/- 0.4 (INR = 1.7), and 15.8 +/- 0.9 (INR = 2.3) seconds for each respective hirudin dosage. Thrombin times were beyond range (> 600 seconds) at 6 hours in all except 2 patients who received the lowest dosage. All parameters returned to baseline between 8 and 18 hours after the infusion. Bleeding times were not significantly prolonged. No side effects occurred. No antibodies to hirudin were detected 2 weeks after the infusion. CONCLUSIONS Recombinant hirudin has a terminal half-life of 2 to 3 hours. The aPTT correlates well with plasma levels of hirudin and allows close titration over a wide range of anticoagulation, while ACT and prothrombin time are relatively insensitive for monitoring hirudin administration. At anticoagulant levels effective in experimental thrombosis, a 6-hour infusion of hirudin is well tolerated and safe in a predominantly male group of patients with stable coronary atherosclerosis.
منابع مشابه
بررسی کیفیت زندگی بیماران نامزد جراحی بای پس عروق کرونر در شهر زنجان
Introduction and purpose: Coronary artery disease is a common chronic disease which has significant effects on various aspects of health including quality of life. The aim of this study was to assess quality of life among patients undergoing coronary artery bypass graft surgery. Materials and Methods: Tis descriptive cross-sectional study was done among 64 hospitalized patients suffering fro...
متن کاملThe Effect of Mindfulness-Based Stress Reduction on Anxiety and Stress in Patients with Coronary Heart Disease after Coronary Artery Bypass Graft Surgery: A Single-Subject Study
Background and objectives: Coronary artery disease (CAD) is associated with negative emotions of anger and stress, which are one of the nonclinical risk factors of the disease. Therefore, evaluation of the effective therapeutic models alleviating the patients’ negative emotions is of paramount importance. This study aimed to examine the effect of mindfulness-based stress reduction (MBSR) on ang...
متن کاملبررسی تأثیر خودمراقبتی معنوی به شیوه گروهی بر امید به زندگی در مبتلایان به بیماری عروق کرونر: یک کارآزمایی آموزشی
Background and Objective: Spiritual self-care is defined as a set of exercises based on spirituality to promote healing in times of sickness and health. Patients' perception of the role of spiritual self-care can lead to chronic disease management. Life expectancy is an important criterion to reflect the mortality impact on longevity and disease in a population. Studies have shown that patients...
متن کاملThe Relation between beliefs about medicines and treatment adherence among patient with Coronary artry disease
Objective: Adherence to drug treatment in patients with coronary artery disease is very important because of the need for long-term use of drugs and the consequences of non-adherence. Several factors may play a role in drug adherence. In this study, the effect of drug therapy-related beliefs on adherence to drug therapy in patients with coronary artery disease was investigated. Material and Met...
متن کاملChanges in Serum Levels of FABP4 and HsCRP after Administration of Omega-3 Fatty Acids Separately or + Vitamin E in Patients with Coronary Artery Disease
Background and purpose: Inflammatory markers of A-FABP and HsCRP play an important role in progression of cardiovascular disease. Anti-inflammatory and anti-platelet aggregation effects of omega-3 fatty acids are known. The aim of this study was to investigate the effects of omega-3 and omega-3+ vitamin E supplements on serum levels of these inflammatory markers. Materials and methods: This d...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Circulation
دوره 88 5 Pt 1 شماره
صفحات -
تاریخ انتشار 1993