Bivalirudin had beneficial effects that were similar or modestly better than heparin in small clinical trials in patients with acute coronary syndrome and those under¬going PCI, but superiority over heparin needs to be tested in large randomized trials. This agent binds reversibly to thrombin, which may explain the lower adverse effects compared with hirudin and heparin.
The plasma half-life of intravenous administration of bivalirudin is 24 minutes. This short half-life is an advantage over hirudin. Also, the drug is only partially excreted by the kidneys, and this allows a greater mea¬sure of safety. In a randomized clinical trial in patients undergoing PCI, bivalirudin reduced the risk of death or MI 30% at 50 days with 60% reduction in major bleeding.
Ximelagatran is the first in a new class of oral direct thrombin inhibitors under investigation for prevention and treatment of thromboembolic events. After oral adminis¬tration the drug is rapidly metabolized to its active form, melagatran, a direct thrombin inhibitor of soluble and fibrin bound thrombin.
In the ESTEEM trial, a placebo-controlled, double-blind randomized multinational study of 1883 patients with acute ST segment elevation or non-ST segment elevation MI was undertaken. The drug significantly reduced the risk for the primary end point (all-cause death, nonfatal infarction, and severe recurrent ischemia) compared with placebo from 16.2% to 12.7%, p ¼ 0.036. All patients received aspirin. No serious clinical adverse outcomes were observed but mild elevation of liver enzymes occurred rarely with ximelagatran administra¬tion. In the SPORTIF III trial alanine aminotransferase elevations reached greater than five times the upper limit of normal in 3.4% of patients, and caution is required. Patients should be carefully monitored for hepatotoxicity which limits general application of this drug. Similar acting agents should be sought (see chapter Atrial Fibrillation).

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