On the go: Clot buster-blood thinner ambulance combo may jump-start heart attack treatment

American Heart Association
Tuesday, 8 July 2003

Combining a clot buster with a form of the blood thinner heparin can be safely initiated for heart attack victims enroute to the hospital – an approach that reduces the time to treatment and could significantly improve survival, according to a rapid track study in today's Circulation: Journal of the American Heart Association.

Rapid track articles are released online early because they have major clinical or population impact or represent important basic science discoveries.

Researchers for the international study – the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-3 PLUS – tested the clot-busting drug tenecteplase with two different blood thinners. They recruited 1,639 patients who had ST-elevation heart attack. This refers to the ECG results that identify the patient as one who needs arterial blood flow restored rapidly.

Patients were randomly assigned to one of two treatment regimes. One consisted of tenecteplase plus one 30 milligram injection of enoxaparin enroute to the hospital followed by 1 milligram per kilogram of enoxaparin twice a day for up to seven days at the hospital. The other treatment was tenecteplase plus weight-adjusted unfractionated heparin infusion enroute to the hospital, followed by heparin infusions for up to 48 hours at the hospital.

"Paramedics make the diagnosis on the scene and they are in telephone contact with a physician. The paramedics electronically transmit results of an electrocardiogram (ECG) to the supervising physician. The accuracy of this diagnosis method is very high," says lead author Lars Wallentin, M.D., professor of cardiology, Uppsala University Hospital, Sweden.

In the study, once the diagnosis was made, paramedic gave a dose of tenecteplase and an injection of one of the blood-thinning agents before the patient reached the hospital.

"We performed the current trial to compare the efficacy and safety of the two antithrombin combination therapies with tenecteplase in the prehospital setting," says co-author Bertil Lindahl, M.D., Ph.D.

Each minute the heart is deprived of blood means more heart muscle is damaged. "What is so unique about this approach is that we are delivering treatment within about two hours of the heart attack, compared to a three-hour time to treatment with hospital-based therapy," Wallentin says.

The median time to treatment in the study was 115 minutes, and 53 percent of patients were treated in less than two hours.

Both 30-day death rates and second heart attacks or ischemic events during hospitalization were lower among patients treated with enoxaparin and unfractionated heparin, but this difference did not reach statistical significance. However, enoxaparin was associated with a significant increase in total stroke (2.90 percent versus 1.30 percent) and intracranial hemorrhage (2.20 percent versus 0.97 percent).

"This was most common in patients over age 75, which suggests the need to test lower doses of enoxaparin in older patients," he says.

Wallentin says a U.S. study will test the effect of a lower enoxaparin dose in the elderly using 75 percent of the dose used in this study. "We think this a good approach and 75 percent for patients 75 years old makes it easy to remember."

Because of the higher complication rate with enoxaparin, researchers say that tenecteplase and unfractionated heparin should be the routine treatment combination in the prehospital setting at the present time.

Other co-authors are P. Goldstein, M.D., Ph.D.; P.W. Armstrong, M.D., Ph.D.; C. B. Granger, M.D., Ph.D.; A.A.J. Adgey, M.D., Ph.D.; H.R. Arntz, M.D., Ph.D.; K. Bogaerts, MSC; T. Danays, M.D.; M. Mäkijävi, M.D., Ph.D.; F. Verheugt, M.D., Ph.D.; and F. Van de Werf, M.D., Ph.D.

For more information, or to contact American Heart Association, see their website at: www.americanheart.org