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Circulation. 2004;109:e9039-e9040
doi: 10.1161/01.CIR.0000131446.36265.86
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(Circulation. 2004;109:e9039-e9040.)
© 2004 American Heart Association, Inc.

Cardiovascular News

Ruth SoRelle, MPH

Circulation Newswriter

Refecoxib Use Increases Acute Myocardial Infarction Risk

Use of refecoxib was associated with a higher relative risk of acute myocardial infarction among elderly subjects than was the use of celecoxib in a study reported in this week’s issue of the journal Circulation ( Circulation. 2004;109:2068–2073[Abstract/Free Full Text]). However, the risk was elevated only in the first 90 days of use, said the researchers led by Daniel H. Solomon, MD, MPH, of the Brigham and Women’s Hospital and Harvard Medical School in Boston, Mass.

Both drugs are common versions of cyclooxygenase-2 inhibitors developed as substitutes for nonsteroidal antiinflammatory medications. The cyclooxygenase-2 inhibitors appear to have a less deleterious effect on the gastrointestinal lining than do the nonsteroidal antiinflammatory drugs known as NSAIDs. Dr Solomon and his colleagues said that there have been concerns about the cardiovascular safety of the use of such drugs in older patients. For that reason, they decided to look at risk of acute myocardial infarction in Medicare patients who used celecoxib, rofecoxib, and NSAIDs. The subjects all had a comprehensive drug benefit that indicated use of the prescribed medications.

The matched case-control study involved 54 475 patients who received medications through 2 state-sponsored drug benefit programs. A total of 10 895 acute myocardial infarctions were identified and then matched to controls. The researchers attempted to assess the relative risk of myocardial infarction in patients who used rofecoxib compared with those who took no NSAID, those who took celecoxib, and those who took NSAIDs.

They found that current use of refecoxib was associated with an elevated relative risk of myocardial infarction compared with taking celecoxib (odds ratio of 1.24) and taking no NSAID (odds ratio 1.14). Celecoxib was not associated with an increased relative risk of acute myocardial infarction.

The researchers advised: "Because of the important potential public health implications, our findings should be followed up by additional clinical and mechanistic studies, several of which are ongoing."

Probable Loci for Familial Abdominal Aortic Aneurysm Identified
A genome scan and genotyping has identified 2 susceptibility loci for familial abdominal aortic aneurysm on chromosomes 19q13 and 4131, according to researchers from Wayne State University School of Medicine in Detroit, Mich, in a report in this week’s issue of Circulation (Circulation. 2004;109: 2103–2108).

In a study led by Hidenori Shibamura, MD, PhD, the researchers performed a whole-genome scan using affected-relative-pair linkage analysis. The technique allows for genetic heterogeneity. This search found evidence of linkage near a marker on chromosome 19 in studies of 36 families. Genotyping of 83 more families for the same and additional markers increased the probability that the chromosome 19 linkage is valid and located the second locus on chromosome 14.

The researchers wrote, "It is likely that additional AAA [abdominal aortic aneurysm] loci will be identified by testing other possible covariates, such as smoking, hypertension, and coronary artery disease, which was not possible in this study because these risk factors are so common both in the general population and in patients with AAA that the relatively small number of families in this study did not provide enough power to study them."

Another Drug for Heart Failure
The drug tolvaptan may be an important addition to current standard treatment for heart failure, said researchers in the April 27, 2004, issue of the Journal of the American Medical Association ( JAMA. 2004;291:1963–1971[Abstract/Free Full Text]). The researchers, led by Mihai Gheorghiade, MD, of Northwestern University Feinberg School of Medicine in Chicago, Ill, noted that the drug is thought to relieve the symptoms of heart failure without affecting electrolytes adversely or damaging kidneys.

The study, called Acute and Chronic Therapeutic Impact of a Vasopressin Antagonist in Congestive Heart Failure (ACTIV in CHF), enrolled 319 patients at 45 centers in the United States and Argentina. All patients had serious heart failure despite standard therapy.

The patients were admitted to the hospital and assigned to receive 30, 60, or 90 mg of tolvaptan, an oral medication, or placebo in addition to the standard medications. They continued on the study drug for as long as 60 days.

Tolvaptan along with the standard treatment, which included diuretics, increased the loss of fluid. As a result, body weight was decreased more effectively than with standard treatment alone. However, the drug did not reduce the risk of heart failure getting worse after discharge from the hospital, the researchers noted.

In an accompanying editorial (JAMA. 2004;291:2017–2018), Gary S. Francis, MD, and W.H. Wilson Tang, MD, both of the Cleveland Clinic Foundation, noted that the lack of a clinical effect could be problematic, particularly when the drug is considered for reimbursement by government agencies or insurers. "Heart failure researchers are still struggling to identify a measure of improved clinical outcome in the setting of acute heart failure that is objective, quantitative, reproducible, relevant and reliable," they wrote.

Baby, It’s Cold Outside and Your Cholesterol is High
Cholesterol levels reach their peak in the winter months, said researchers in the April 26, 2004, issue of the Archives of Internal Medicine ( Arch Intern Med. 2004;164:863–870[Abstract/Free Full Text]). Actually, levels vary with the seasons, said the researchers led by Ira S. Ockene, MD, of the University of Massachusetts Medical Center in Worcester.

The researchers studied the variations in cholesterol among 517 healthy volunteers in a health maintenance organization. Data were collected every 3 months over a 12-month period. The information included diet, physical activity, exposure to light, general behavioral statistics, and cholesterol levels. The levels were measured at each data collection point.

The average cholesterol level was 222 mg/dL in men and 213 mg/dL in women. During the period, cholesterol levels increased by 3.9 mg/dL in men with a peak in December and by 5.4 mg/dL in women, peaking in January. Twenty-two percent more of those who participated had cholesterol levels that exceeded the threshold for hyperlipidemia during the winter months than during the summer.

The difference could not be explained by seasonal changes in dietary intake or in the total number of calories consumed, they wrote. However, they said, the changes appear to be related to differences in physical activity or temperature between winter and summer.

They advised further researcher to understand how these factors affect cholesterol levels.




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E. Fosslien
Cardiovascular Complications of Non-Steroidal Anti-Inflammatory Drugs
Ann. Clin. Lab. Sci., October 1, 2005; 35(4): 347 - 385.
[Abstract] [Full Text] [PDF]


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