American College of Cardiology

**Estrogen-receptor modulator may improve cardiovascular risk factors in postmenopausal women

(ORLANDO, FLA.)—Past studies have found that estrogen replacement therapy can reduce blood cholesterol levels but does not prevent—and may even increase—cardiac risk in postmenopausal women. The possible cardiovascular effects of raloxifene, a selective estrogen-receptor modulator, have not been as widely studied.

Now, a large, placebo-controlled study of raloxifene, primarily a test of its effect on osteoporosis, has found that the drug also can improve serum cholesterol and other laboratory markers of cardiovascular risk in postmenopausal women. During the three years of follow up in the "Multiple Outcomes of Raloxifene Evaluation" (MORE) trial, raloxifene therapy was associated with neither an increase nor a decrease in the risk of clinical events, such as heart attack or stroke.

Dr. Elizabeth Barrett-Connor, professor of epidemiology in the Department of Family and Preventive Medicine, University of California, San Diego, is scheduled to present the MORE results at 8:30 a.m. on Wednesday, March 21, at the American College of Cardiology 50th Annual Scientific Session in Orlando, Fla.

Because the potential for increased event risk with estrogen replacement therapy was observed in earlier studies during the first year of treatment, the encouraging three-year MORE results open the door for further research of raloxifene for the prevention of heart disease in postmenopausal women.

Low-molecular-weight heparin helps streptokinase restore and maintain coronary flow in patients with heart attack

(ORLANDO, FLA.)—Enoxaparin, a recently introduced blood thinner, can enhance the ability of streptokinase thrombolytic therapy to restore and maintain coronary flow in patients with evolving heart attacks, according to a randomized, placebo-controlled trial.

Thrombolytic agents dissolve the blood clots that block coronary artery flow and trigger heart attacks, but reblockage is a frequent problem. Heparin, the standard intravenous blood thinner, can help keep the arteries open but it is not always used and treatment guidelines do not require it.

In the "Acute Myocardial Infarction-Streptokinase" (AMI-SK) trial, enoxaparin—a chemical variant of heparin that is easier and more predictable to use—seemed highly effective at preserving coronary flow in patients with heart attacks treated with streptokinase.

The study suggests that "the use of enoxaparin with streptokinase can improve patients' clinical outcome by producing better reperfusion, better infarct-related artery patency, and less reocclusion than streptokinase alone," said Dr. Angeles Alonso, chief of the coronary care unit at Clinica Puerta de Hierro, Madrid, Spain.

Dr. Alonso is scheduled to present safety and efficacy results and 30-day clinical outcomes from the AMI-SK trial on Wednesday, March 21, at 8:45 a.m. at the American College of Cardiology 50th Annual Scientific Session in Orlando, Fla.

**Statin appears to reduce inflammatory markers in patients with cardiovascular risk factors

(ORLANDO, FLA.)—Statin drugs, now widely given to people with elevated blood cholesterol to reduce their risk of heart attacks and stroke, seem to work by reducing arterial inflammation as well as lowering cholesterol. But most of the evidence suggesting that the anti-inflammatory effects of statins play a role in their benefits has been inconclusive.

Now, for the first time, a randomized trial has shown prospectively that treatment with a statin agent, pravastatin, significantly reduces blood levels of C-reactive protein (CRP), an indicator of inflammation, in persons at risk for cardiovascular disease. The findings, according to Dr. Paul M. Ridker, have immense implications for the treatment of millions of Americans who have elevated CRP levels but apparently normal cholesterol levels.

Elevated CRP levels reflect the presence of ongoing inflammation, which is known to play a role in the development of heart disease. Retrospective analyses have strongly suggested that pravastatin, and perhaps other statin drugs, have an anti-inflammatory effect indicated by reductions in CRP levels.

But the placebo-controlled "Pravastatin Inflammation/CRP Evaluation" (PRINCE) trial was intentionally designed to show whether pravastatin can reduce CRP levels. Not only does the drug have that effect, according to the PRINCE findings, but it does so independently of its well-recognized cholesterol-lowering effects, said Dr. Ridker, of Brigham and Women's Hospital, Boston.

Dr. Ridker is scheduled to present the results of the PRINCE trial at 9 a.m. on Wednesday, March 21, at the American College of Cardiology 50th Annual Scientific Session in Orlando, Fla.

**Invasive management is more effective and no more costly than conservative care for acute coronary syndromes

(ORLANDO, FLA.)—Last year the TACTICS-TIMI-18 trial found that routine invasive management of patients with acute coronary syndromes, a limited form of heart attack, was more effective at preventing later cardiac events than a more conservative "wait-and-see" approach. Now, an economic analysis from the same trial has found that invasive care can provide those clinical benefits in a cost-effective way.

Whether acute coronary syndromes should be managed invasively—with early cardiac catheterization, including angioplasty as needed—or more conservatively—with catheterization only if symptoms recur or get worse-has long been debated. Investigators from the TACTICS-TIMI-18 study ("Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Strategy") previously reported that the risk of later clinical events, including death, was significantly lower with invasive management. The study was among the first of its kind to be performed using such contemporary treatments as coronary stents and platelet glycoprotein IIb/IIIa receptor inhibitors-drugs that discourage blood platelets from clumping to form clots.

The trial's economic analysis, according to Dr. William Weintraub of Emory University, Atlanta, "shows that the benefits of an invasive strategy in acute coronary syndromes can be achieved at essentially no increase in cost."

Dr. Weintraub is a professor of health policy and management at Emory and director of the university's Center for Outcomes Research. He is scheduled to present the economic analysis of TACTICS-TIMI-18 at 9:15 a.m. on Wednesday, March 21, at the American College of Cardiology 50th Annual Scientific Session in Orlando, Fla.

**Chelation therapy for coronary disease is tested in randomized trial

(ORLANDO, FLA.)—Chelation therapy, which can help rid the body of toxic heavy metals, is widely used in the alternative-medicine community for the treatment of many illnesses. Although some limited data suggests that the chelation agent EDTA may be effective against coronary artery disease, the treatment has never been tested in a randomized, controlled trial, until now.

EDTA, or ethylendiamine tetra acetic acid, has been used for more than 60 years for the treatment of heavy metal poisoning, such as by mercury or lead. Suggestions that it may also increase the body's elimination of calcium and other elements involved in atherosclerosis led to its widespread use as an alternative coronary disease treatment, observed Dr. Merril L. Knudtson, of Foothills Hospital, Calgary, Canada.

Whether EDTA can improve symptoms and other measures of well-being in patients with documented heart disease was the focus of the placebo-controlled "Program to Assess Alternative Treatment Strategies to Achieve Cardiac Health" (PATCH) trial. Outcomes in the 80 randomized patients were assessed by exercise stress testing, various measures of vascular function and a battery of tests designed to gauge changes in quality of life, said Dr. Knudtson.

The PATCH trial is scheduled to be presented by Dr. D. George Wyse of the University of Calgary, at 9:30 a.m. on Wednesday, March 21, at the American College of Cardiology 50th Annual Scientific Session in Orlando, Fla.

Endothelin-receptor blockade again shows no benefit as treatment for chronic heart failure

(ORLANDO, FLA.)—A class of drugs that blocks receptors for endothelin, one of the body's natural vasoconstricting agents, has once again proven ineffective for the treatment of chronic heart failure in a randomized trial.

Endothelin-receptor antagonists can relax the walls of blood vessels so they carry blood more freely, but their mode of action is different from that of such common heart failure drugs as angiotensin-converting enzyme inhibitors or beta blockers. They, therefore, have been viewed as a promising potential new addition to current medical therapies for patients with chronic heart failure, according to Dr. William T. Abraham, chief of cardiovascular medicine at the University of Kentucky, Lexington.

However, in a randomized study of patients with moderate heart failure who were followed for up to nine months, the addition of the endothelin-receptor antagonist enrasentan to standard medications provided no further treatment benefits. The findings, said Dr. Abraham, are consistent with earlier research on another nonselective endothelin-receptor antagonist, bosentan, in a similar patient group.

Although the two studies together "raise a cautionary flag regarding the use of nonselective endothelin antagonists, they suggest a need for ongoing investigation of more selective endothelin receptor blockers," which might be more effective as a heart failure therapy, said Dr. Abraham. He is scheduled to present the results of the enrasentan trial, called ENCORE, at 9:45 a.m. on Wednesday, March 21, at the American College of Cardiology 50th Annual Scientific Session in Orlando, Fla.

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