NR 98-4836 (Circ/Van Belle)
DALLAS, Jan. 13 -- A new study raises the surprising possibility that physicians may not be treating the aftermath of their patients' heart attacks aggressively enough. The findings appear in today's Circulation: Journal of the American Heart Association.
French researchers peering into diseased segments of the blood vessels of people who've had heart attacks found that fatty growths called plaques, which have ruptured and produced blood clots that cause heart attacks, remain dangerously unstable for a longer time after the heart attack than was previously realized.
Unstable plaques are like unhealed sores which continue to stimulate blood clot formation that can once again obstruct the vessel, restricting blood flow to the heart to cause additional heart damage.
It had been thought that these ruptured plaques healed within days or few weeks after the heart attack. But often, an individual can have an active disease state continue for weeks even when no symptoms are present, the study showed. The discovery could lead doctors to consider extending their therapy for recovering patients to include at least a month and possibly longer.
"This is a very significant finding," says Richard W. Smalling, M.D., Ph.D, cardiologist and researcher at the University of Texas Medical School at Houston. "It will make us look hard at the treatment procedures currently in use for recovering heart attack patients."
Plaques have been known to be unstable, with blood clots sticking to their surface during the first few hours after a heart attack, notes Smalling, author of a Circulation: Journal of the American Heart Association commentary on the new study. The finding that the plaques remain active for up to 30 days, despite "intense" anti-clot therapy including aspirin and the blood-thinner heparin, "is quite interesting and unsettling," writes Smalling, professor of medicine at the UT-Houston Medical School and chief of cardiology at Hermann Hospital.
This study says that these patients are at risk for at least 30 days and probably longer, he says. Thus, 12-hour anti-platelet therapy is not enough. "Aggressive platelet blockade ought to be tested for at least a month and perhaps as long as six months" after a heart attack, "since we don't know how long it will take for that plaque to pacify itself and heal." Platelets are disc-shaped blood elements that the body summons to the site of an injury to clump into clots and halt bleeding. In this instance, however, the process creates a vessel blockage.
Investigators at the Hopital Cardiologique in Lille, France, led by Eric Van Belle, M.D., Ph.D., examined diseased arteries in 56 heart attack patients, most of them men, with an average age 55. Forty of the patients were initially treated with a clot-busting drug. Using a sophisticated device called an angioscope, researchers could to see inside vessels and inspect the surface of plaques at the site of blockages that had caused heart attacks. Riding through arteries on a thin wire, the angioscope records them on videotape. Images of patients' target artery segments that were taken up to four weeks after their heart attacks showed:
- In 77 percent of the patients, blood clots were visibly protruding from blood vessel walls;
- More than half of the plaques (54 percent) were irregular in shape with jagged edges rather than a smooth surface that would signal healing, and a third (36 percent) were ulcerated;
- More than three-fourths of plaques (79 percent) were yellow -- a color associated with heightened biologic activity and a higher incidence of recurring blockages.
Despite this high incidence of ominous signs of disease activity, only seven percent of the patients had "unstable" angina -- the severest type of heart pain that occurs even while the patient is at rest. The French team says the results of their study show that angioscopic evidence of plaque instability lasts during the month after a heart attack "even in asymptomatic patients and in patients initially treated with thrombolysis [clot-busting drugs]."
While the researchers found less evidence of clotting in patients who had received clot-busting drugs, clots that were present in those patients were more likely to be ulcerated.
Smalling says the persistence of clotty, unstable plaques points to the need for more effective anti-platelet therapy, including use of a new family of drugs called glycoprotein IIb/IIIa receptor antagonists, which work via a different biologic pathway to interfere with platelet activity at the site of a ruptured plaque. That's where raw exposure to blood remains after conventional clot-busting drugs have dissolved the original clot.
"Blocking the IIb/IIIa receptor is key," he says. "Even though the thrombolytic agent dissolved the clot that cause the initial event, cholesterol and other tissue elements are still lying there exposed to the blood flowing past the ruptured plaque which makes it still intensely thrombogenic [clot-prone]."
Additional techniques to calm unstable plaques may include balloon angioplasty and the installation of metal mesh tubes called stents to keep vessels propped open, Smalling points out.
Another result of the new findings, he says, is a realization that faster-acting clot-busters may be less effective, overall, than previously thought. Since the new study shows that plaques remain active long after administration of the quick-acting types of drugs, "the early advantage of a faster [drug] may have been lost" if the plaque is not stabilized.
Van Belle and his colleagues say their discovery of delayed healing inside a plaque-laden artery after a first rupture provides a possible explanation for the "unique behavior" of those plaques that are more prone to rupture again. They note that other studies have shown that the "unfavorable" features they've documented in their patients' arteries are associated with higher rates of vessel blockages and increased risk of additional heart attacks and death.
Co-authors of the study are Jean-Marc Lablanche, M.D.; Christophe Bauters, M.D.; Nathalie Renaud, M.D.; Eugene P. McFadden, M.R.C.P.I, and Michel E. Bertrand, M.D.
Media advisory: Drs. Van Belle or Bertrand can be reached in France by calling 33-3-20-44-53-02. Fax 33-3-20-53-58-74. Dr. Smalling may be reached in Houston by calling (713) 500-6559.