Hirudin for Acute Coronary Syndromes
April 1, 1999 3 minutes read
Hirudin for Acute Coronary Syndromes
ABSTRACT & COMMENTARY
Synopsis: Hirudin is superior to heparin for preventing cardiac events in the first week after the onset of an acute coronary syndrome.
Source: Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) Investigators. Lancet 1999; 353:429-438.
The organisation to assess strategies for Ischemic Syndromes (OASIS) conducted a pilot trial of patients with unstable angina or non-Q-wave myocardial infarction (MI) and found that hirudin reduced cardiac events over seven days. Thus, a longer study was carried out that compared hirudin to heparin. All 10,141 patients took aspirin and were randomized to standard-dose heparin or medium-dose hirudin (0.4 mg/kg bolus, then 0.15 mg/kg/h infusion) for 72 hours. The primary end point was cardiovascular death or new MI within seven days. The primary end point occurred in 4.2% of the heparin group and 3.6% of the hirudin group (relative risk [RR], 0.84; P = 0.08). If refractory angina is combined with the primary end points, the event was 6.7% with heparin and 5.6% with hirudin (RR, 0.82; P = 0.02). These differences were largely observed during the 72-hour treatment period. More patients in the hirudin group vs. the heparin group had treatment stopped early due to excess bleeding or other adverse events (2.8% vs 1.3%; P < 0.001) and more had major bleeding episodes in general (1.2 vs 0.7%; P = 0.01). Almost all these were in the first 72 hours and due to gastrointestinal bleeding. The incidence of stroke was similar and there was only one hemorrhagic stroke, which occurred in the heparin group. The OASIS investigators conclude that hirudin is superior to heparin for preventing cardiac events in the first week after the onset of an acute coronary syndrome.
Comment by Michael H. Crawford, MD
Unstable angina/non-Q-wave MI remains a common cause for hospital admission, and, despite modern aggressive therapy, 10-15% suffer Q-wave MI or need urgent revascularization for refractory symptoms. Despite these undesirable outcomes, both the TIMI III and VANQWISH trials showed little benefit from an aggressive early revascularization approach. Thus, there has been considerable interest in new pharmacological approaches that more adequately attack the underlying pathophysiology. Platelet IIb/IIIa inhibitors have shown some promise, but the studies have shown inconsistent results vs. heparin therapy. However, the GUSTO IIb, TIMI 9B, and OASIS I studies have exhibited consistent moderate gains of hirudin over heparin therapy. Since most patients with unstable angina receive a cocktail of five or more drugs, the ability of any new drug to affect "standard therapy" is problematic. Remarkably, hirudin showed an approximately 20% decrease in ischemic events in this robust trial.
The rationale for the improved outcomes with hirudin is that it is a direct thrombin inhibitor, whereas heparin is an indirect inhibitor. The hirudin used in this study (lepirudin, Hoechst Marion Roussel, Germany) is a recombinant DNA product derived from the medicinal leech. It inhibits both clot-bound and circulating thrombin. Thus, it is probably not surprising that major and minor bleeding episodes were more common with hirudin, but there was no increase in life-threatening bleeds. Overall, the rate of major bleeding complications was low in this trial (< 2%). This is probably because the rate of percutaneous and surgical revascularization was low (6-7%). In a more aggressively managed patient group, bleeding complications could be more profound.
Cardiac events still occur beyond seven days from the onset of unstable angina despite aspirin and other therapies. For this reason, the investigators in OASIS II are conducting a substudy of long-term warfarin. Also, the issue of continuing hirudin for more than 72 hours, an oral IIb/IIIa agent, or subcutaneous low-molecular-weight heparin for more than seven days should be considered. Clearly, the optimal treatment of unstable angina is unknown, but the pharmacologic possibilities are widening and hirudin appears to be a strong contender to replace intravenous heparin.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content