Best early heart attack treatment is matter of time

American Heart Association
Tuesday, 18 November 2003

What is the best early treatment for heart attack? The answer is a question of time, according to an article in today's rapid access publication of Circulation: Journal of the American Heart Association.

The first randomized comparison of clot-busting drugs given en route to the hospital and balloon angioplasty upon arrival finds that clot-busting drugs (thrombolytic agents) seem preferable for patients treated within two hours of symptom onset. Patients treated two to six hours after their symptoms seem to do better with a percutaneous coronary intervention (PCI). PCI is the scientific name for the procedure in which a balloon-tipped catheter is threaded into the artery and the balloon is gently inflated to push back the blockage and reopen the vessel.

"Several studies have found PCI is associated with better outcomes compared to in-hospital thrombolysis," said Philippe Gabriel Steg, M.D., director of the coronary care unit and an interventional cardiologist at Hôpital Bichat in Paris, France.

However, the benefit of thrombolysis is time-dependent. Doctors speak of the "golden hours," the first two hours after symptoms begin, as the time when thrombolysis is most likely to succeed. Because patients spend some of that time on the way to the hospital, Steg wondered if pre-hospital thrombolysis would make a difference.

France is one of the few places in the world that offers pre-hospital thrombolysis. Emergency medical services (EMS) systems have resisted letting paramedics administer the drug because of the risks of hemorrhage and stroke, Steg said.

In contrast to the EMS systems common in the United States and most other nations, France's compact size and highly urbanized population allow its EMS to stabilize patients before transport to the nearest appropriate hospital, he said. France also has mobile intensive care units (MICUs) staffed by doctors. The MICUs are sent to patients who call "15" (the French version of 9-1-1) complaining of chest pain, he said.

Today's report is a subanalysis of the Comparison of Angioplasty and Pre-hospital

The Thrombolysis in Acute Myocardial Infarction (CAPTIM) study, which included 840 patients treated at 27 hospitals all over France, was coordinated in Lyon, France.

Using a composite endpoint of death, non-fatal second heart attack and non-fatal disabling stroke at 30 days, CAPTIM found results of the two therapies were not different. The average delay from symptom onset to treatment was 2 hours, 10 minutes in the thrombolysis group and 3 hours, 10 minutes in the PCI group. All patients were taken to hospitals that had PCI available and 70.4 percent of the thrombolysis patients underwent PCI within the next 30 days, Steg said.

The current study used data from CAPTIM to investigate the time issue: thrombolysis in two hours vs. PCI in three. It found a strong trend toward lower 30-day death rates in patients randomized to thrombolysis (2.2 percent for thrombolysis versus 5.7 percent for PCI), although it did not reach statistical significance. An often-fatal complication called cardiogenic shock — the heart's failure to pump due to sustained interruption of its blood supply — was much less frequent in the thrombolysis group (1.3 percent) than in the PCI group (5.3 percent) while rates were similar in patients randomized later, he said.

"The fact that we had virtually no shock in the pre-hospital thrombolytic group indicates that opening the vessel prior to hospital arrival is very important to saving the heart muscle," Steg said.

A lack of funding forced the CAPTIM study to recruit fewer patients than planned, which reduced its statistical power, the researchers wrote.

Eugene Braunwald, M.D., Distinguished Hersey Professor of Medicine at the Harvard Medical School, and chairman of the Thrombolysis and Myocardial Infarction (TIMI) Study Group at Brigham and Women's Hospital, commented on the study in an accompanying editorial.

"It is extremely important to get treated very rapidly. Delays in treatment limit the benefits of any of these therapies," Braunwald said. He said the study raises two important questions: "How can we most effectively increase the number of patients who present immediately after the onset of symptoms, and how can we provide pre-hospital fibrinolytic (thrombolysis) therapy in the United States to maximize the benefit of treatment during the golden hours?"

Steg's co-authors are Eric Bonnefoy, M.D.; Sylvie Chabaud, M.Sc.; Frederic Lapostolle, M.D.; Pierre-Yves Dubien, M.D.; Pascal Cristofini, M.D.; Alain Leizorovicz, M.D.; and Paul Touboul, M.D. Braunwald's co-author is Robert G. Giugliano, M.D., S.M.

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