Lepirudin may prevent heart attacks, death

New research shows that unstable angina patients who take lepirudin (Bridgewater, NJ-based Hoechst Marion Roussel’s Refludan) are less likely to have a heart attack, need invasive cardiac procedures, or die compared to patients treated with standard therapy. A study presented in August at the 20th congress of the European Society of Cardiology in Vienna showed that treating heart patients with lepirudin over a three-day period prevents seven additional deaths or heart attacks and 14 invasive interventions for every 1,000 people treated. The study evaluated the effects of lepirudin, a direct thrombin inhibitor, compared to standard heparin, an indirect thrombin inhibitor, in treating patients with unstable angina. More than 10,000 patients were randomly assigned to receive a 72-hour double-blind IV infusion of either heparin or lepirudin.

The combined rate of cardiovascular death and heart attack in the lepirudin group was reduced by 24% at the end of treatment. The rate of cardiovascular death, heart attack, and refractory angina was reduced by 22%. The benefits of lepirudin treatment were maintained throughout the 35-day follow-up period. After treatment was discontinued, deaths, heart attacks, and other events reflecting continued presence of clot in the coronary arteries occurred at the same rate in both groups. In particular, there was no evidence of clinical rebound following drug withdrawal, of concern in other trials of antithrombotic drugs for coronary events.

Lepirudin is a potent anticoagulant that inhibits the enzyme thrombin, which plays a pivotal role in the coagulation cascade leading to clot formation. Unlike heparin, which inhibits thrombin indirectly by activating a protein known as antithrombin III, lepirudin directly blocks the enzyme’s activity not only in the circulation but also in the clot itself.

Regulatory filings are currently in progress. In clinical studies of lepirudin, bleeding from puncture sites and wounds was the most common side effect. Concomitant use with thrombolytics can result in intracranial bleeding. Other events included anemia, hematoma, hematuria, fever, and abnormal liver function.