The low-molecular-weight heparin compound reviparin reduces risk of death or subsequent infarction when given to patients having an acute myocardial infarction, with earliest initiation associated with greatest benefit, according to an article in the January 26th issue of the Journal of the American Medical Association.

Approximately 15.5 million cardiovascular deaths occur every year, according to background information in the article. Of these, about half are likely to be due to acute myocardial infarction. Although reperfusion therapy, aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors reduce the risk of death when used early in patients with an acute myocardial infarction, the rate of death or subsequent morbidity remains high. No antithrombotic or newer antiplatelet drug has been shown to reduce the risk of death after an infarction.

Salim Yusuf, D.Phil., F.R.C.P.C., and his Canadian colleagues evaluated the effects of reviparin on the composite outcome of death, myocardial infarction, and stroke at 7 and 30 days. The randomized, double-blind, placebo-controlled trial (Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment Evaluation [CREATE]), included 15,570 patients with ST-segment elevation or new left bundle-branch block.

The patients presented within 12 hours of symptom onset at 341 hospitals in India and China from July 2001 through July 2004. Patients received reviparin (n = 7,780) or placebo (n = 7,790) subcutaneously twice daily for seven days.

The researchers found that the primary composite outcome was significantly reduced from 11.0 percent of placebo patients to 9.6 percent of reviparin patients, a 13-percent lowered risk. These benefits persisted at 30 days (13.6 percent vs. 11.8 percent) patients, still a 13-percent lowered risk.

There were significant reductions in the 30-day death rate (11.3 percent vs. 9.8 percent, 13-percent lower rate) and additional infarction (2.6 percent vs. 2.0 percent, a 23-percent lower rate). However, there were no significant differences in incidence of stroke (0.8 percent vs. 1.0 percent).

Reviparin treatment was significantly better in terms of 7-day outcome when it was initiated very early after symptom onset (less than 2 hours: 30-percent reduced risk; 30 of 1,000 events prevented; between 2 to 4 hours: 19-percent reduced risk; 21 of 1,000 events prevented; between 4 to 8 hours: 15-percent reduced risk; 16 of 1,000 events prevented; and greater than 8 hours: 6-percent increased risk).

There was an increase in life-threatening hemorrhage at 7 days with reviparin (17 [0.2 percent] vs. 7 [0.1 percent]), but the absolute excess was small (1 more event per 1,000) compared with the reductions in the primary outcome (18 fewer per 1,000) or mortality (15 fewer per 1,000).

“Reviparin is considerably less expensive than other antithrombotic agents, such as bivalirudin, … and can be given subcutaneously. Its use is relatively straightforward and can be used in both developed and developing countries. Therefore, the benefits of reviparin represents a moderate but important globally applicable advance in the management of patients with acute myocardial infarction,” the authors concluded.