Drug reviparin reduces the risk of death after heart attack

Jan 26 2005

The drug reviparin (a low molecular weight heparin anticoagulant), when administered to patients with a heart attack, is effective in reducing the risk of death and the risk of a subsequent heart attack, according to a study in the January 26 issue of JAMA.

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 (MI, [heart attack]). Although reperfusion therapy (restoration of blood flow), aspirin, beta-blockers, and angiotensin-converting enzyme (ACE) inhibitors reduce the risk of death when used early in patients after a heart attack, the rate of death and illness remains high. No antithrombotic or newer antiplatelet drug has been shown to reduce the risk of death after a heart attack.

Salim Yusuf, D.Phil., F.R.C.P.C., of Hamilton General Hospital and McMaster University, Ontario, Hamilton, Canada, and colleagues evaluated the effects of reviparin on the composite outcome of death, heart attack, 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 (a specific finding on the electrocardiogram ) or new left bundle-branch block (a slowing in the flow of electrical pulses that drive the heart beat). 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 patients in the placebo group to 9.6 percent in the reviparin group, a 13 percent lowered risk. These benefits persisted at 30 days (13.6 percent vs. 11.8 percent) patients, a 13 percent lowered risk; with significant reductions in the 30-day death rate (11.3 percent vs. 9.8 percent), 13 percent lower rate; and additional heart attack (2.6 percent vs. 2.0 percent), a 23 percent lower rate; and no significant differences in strokes (0.8 percent vs. 1.0 percent).

Reviparin treatment was significantly better when it was initiated very early after symptom onset at 7 days (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 bleeding at 7 days with reviparin and placebo (17 [0.2 percent] vs. 7 [0.1 percent], respectively); 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 MI," the authors conclude.

In a related study in this week's JAMA, a widely applicable, inexpensive therapy was found to have no effect on death rates when treating patients who had an acute ST-segment elevation myocardial infarction (STEMI), a heart attack with a specific finding on the electrocardiogram.

Shamir R. Mehta, M.D., M.Sc., of McMaster University and Hamilton Health Sciences, Hamilton, Ontario, Canada, and colleagues evaluated the effects of high-dose glucose-insulin-potassium (GIK) infusion on patients with acute STEMI. GIK is a low-cost therapy that has been speculated to improve mortality in heart attack patients.

The study (a merger of CREATE and Estudios Cardiologicas Latin America Study Group, ECLA [CREATE-ECLA]) was conducted in 470 centers worldwide among 20,201 patients with STEMI who presented within 12 hours of symptom onset. The average age of patients was 58.6 years, and evidence-based therapies were commonly used. Patients were randomly assigned to receive GIK intravenous infusion for 24 hours plus usual care (n = 10,091) or to receive usual care alone (controls; n = 10,110).

The researchers found: "The CREATE-ECLA trial demonstrated that high-dose GIK solution given for 24 hours in patients presenting with acute STEMI has a neutral effect on mortality, cardiac arrest, and cardiogenic shock. The goal of our study was to reliably assess the effects of high-dose GIK in preventing mortality and major cardiovascular events in patients with STEMI. Given that there were more than 1,900 deaths in the study, it was well powered to detect even a moderate effect on mortality," the authors write. "The very high adherence to the protocol and the excellent 30-day follow-up (99.85 percent) provide confidence in the validity of our findings and suggest that it is very unlikely that the current regimen of high-dose GIK is of any material benefit in reducing mortality in patients with STEMI."