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Trial Supports Early, Aggressive Statin Use After Heart Attack

Trial Supports Early, Aggressive Statin Use After Heart Attack
Trial Supports Early, Aggressive Statin Use After Heart Attack


Duke Health News Duke Health News

DURHAM, NC -- Patients suffering from acute coronary syndromes should be treated with cholesterol-lowering drugs known as statins early and aggressively, according to the results of an international clinical trial led by a team of investigators at the Duke Clinical Research Institute, the University of Texas Southwestern Medical Center and the Brigham and Women's Hospital.

The benefits of statins in reducing the risk of heart attacks have been demonstrated in patients with stable coronary artery disease or those at risk for a future heart attack. However, the current trial was one of the first to examine the benefits of giving patients statins in the hospital shortly after treatment for their heart attack symptoms.

In the past, physicians have traditionally taken a patient approach to cholesterol lowering in their heart patients after discharge from the hospital, researchers said. Typically, physicians have tried to lower cholesterol levels by beginning with dietary approaches and then slowly adding or increasing the use of statins, they said.

"The results of the current trial, as well as two previous trials, suggest that an early and aggressive use of statins can reduce the long-term incidence of heart attacks, death from heart attack, stroke or readmission to the hospital for a cardiac event," said Duke cardiologist Michael Blazing, MD.

He presented the results of the trial Aug. 30, 2004, at the annual scientific sessions of the European Society of Cardiology meeting in Munich. Joining Blazer was co-investigator James de Lemos, MD, from The University of Texas, Southwestern Medical Center, Dallas.

Based on the results of previous clinical trials, the National Cholesterol Education Program in July issued new guidelines calling for a more aggressive approach to lowering levels of LDL cholesterol -- the so-called bad form of cholesterol -- in heart patients, especially those at high risk.

The current trial, which was conducted in two parts, was dubbed "A to Z" (Aggrastat to Zocor). The "A" portion, which was completed two years ago, compared the effectiveness of two different forms of heparin -- enoxaparin or unfractionated heparin -- in preventing complications after a first heart attack.

The "Z" portion of the trial compared two approaches -- a delayed, lower-dose approach and an early, aggressive approach to using the statin simvastatin (trade name Zocor). Like other statins, simvastatin works by lowering the levels of LDL cholesterol.

A total of 4,497 patients who arrived at the hospital with chest pain were enrolled at 322 sites in 41 countries, with about 20 percent of the patients enrolled in the U.S. After treatment, the patients randomized to the early, aggressive arm of the trial received 40 mg of simvastatin for 30 days, followed by 80 mg a day. The other half of the patients received a placebo for four months, followed by 20 mg of simvastatin a day. Patients were followed for at least six months and up to 24 months.

"After two years, we found that 14.4 percent of those treated early and aggressively had had a heart attack, stroke, cardiovascular death or readmission, compared to a 16.7 percent rate in the conservative arm," Blazing said, adding that while each of the individual endpoints were lower in the aggressively treated group, the differences fell just short of achieving statistical significance.

Statistical significance was achieved, however, in the difference between patients developing congestive heart failure -- 3.7 percent in the aggressively treated group compared to 5 percent in the conservatively treated group. There were also strong trends favoring the aggressive simvastatin arm for the endpoint of cardiovascular death.

Interestingly, there were no differences in endpoints between the two groups during the first four months of the trial, with the benefits from the higher doses becoming evident longer term, said Blazing.

One important side effect of statin usage is muscle pain. In the current trial, the researchers found that the aggressively treated patients experienced a slightly higher incidence of muscle disorders known as myopathies (0.4 percent). However, the researchers added, the levels of side effects were consistent with the known rates of myopathy with the drugs used in the study, and no cases of myopathy were found with dosages of simvastatin below 80 mg.

Specifically, 1.8 percent of those in the aggressively treated arm had to discontinue the drug for muscle-related symptoms, compared to 1.5 percent for the conservative arm. Nine patients treated aggressively had actual myopathies, compared to one in the conservative arm.

"Physicians should be aware that these higher doses of statins are associated with a higher incidence of myopathy than is seen at lower doses," de Lemos said. "However, the small risk appears to be outweighed by the benefits of the more aggressive cholesterol-lowering strategy in reducing death and major complications such as second heart attacks and the development of heart muscle weakness."

A to Z was sponsored by Merck & Co., Whitehouse Station, NJ, the maker of simvastatin. Blazing has received honoraria as a speaker for Merck.

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