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MUNICH -- Treating patients with extended-release fluvastatin before and after they underwent elective major peripheral vascular surgery halved the postsurgical rate of cardiac death and myocardial infarctions in a randomized, controlled study including about 500 patients.

The 80-mg/day dosage of fluvastatin XL used in the study was "completely safe" and led to reductions in inflammatory markers, suggesting that the treatment's benefit was because of coronary-plaque stabilization and prevention of plaque rupture following the stress of surgery, Dr. Don Poldermans said in his presentation at the annual meeting of the European Society of Cardiology.

Fluvastatin XL is the only extended-release statin formulation currently marketed, and the drug was chosen to give patients ongoing drug coverage during and immediately after surgery when they would be otherwise unable to receive an oral statin, said Dr. Poldermans, who is a professor of anesthesiology at Erasmus University Medical Centre in Rotterdam, the Netherlands.

"This is important new information that was validated by a randomized, controlled trial. It's a very good study," commented Dr. Timothy Gardner, who is a cardiothoracic surgeon and the medical director of the Center for Heart and Vascular Health at Christiana Care in Wilmington, Del.

"The results will require us to look at the issue of preoperative statins in vascular surgery patients and maybe change our guidelines," he added. Current guidelines from the American College of Cardiology and American Heart Association rate statin use in vascular surgery patients as a IIB indication; the new data "may allow it to be bumped up to IIA," Dr. Gardner said in an interview.

In a previous report, Dr. Poldermans and his colleagues showed that statin discontinuation around surgery was associated with an increased risk for postoperative troponin release (hazard ratio 4.6) and the combination of myocardial infarction and cardiovascular death (hazard ratio 7.5) (Am. J. Cardiol. 2007;100:316-20). In that study, they reported that the use of fluvastatin appeared to provide a protective effect, prompting further investigation.

The Dutch Echographic Cardiac Risk Evaluation Applying Stress Echo (DECREASE) III trial randomized patients who already were on optimal medical treatment that did not include statin therapy to either fluvastatin XL or placebo starting an average of 37 days before their scheduled surgery.

Treatment continued until at least 30 days following surgery but was interrupted for as long as patients were unable to take an oral pill during and after surgery.

Fluvastatin treatment led to modest, average drops of about 20% in both total and LDL cholesterol levels, but these reductions were significantly greater than were the average 3%-4% reductions in the placebo patients.

The patients on active treatment also had an average 21% decline in their serum level of C-reactive protein, and an average 33% fall in their serum level of interleukin-6, significantly greater changes than in patients on placebo.

During the first 30 days following surgery, the incidence of myocardial ischemia, the study's primary end point, was 19% among the 247 placebo patients and 11% in the 250 fluvastatin XL-treated patients, a statistically significant difference.

The study's secondary end point, the combined rate of myocardial infarction and cardiac death, occurred in 10% of placebo patients and 5% of those on fluvastatin XL, also a statistically significant difference.

Additional analysis showed that treating 19 patients with fluvastatin XL avoided one episode of either cardiac death or myocardial infarction (see chart).

The fluvastatin XL regimen was not associated with an increased incidence of any side effects compared with the placebo patients, including no excess episodes of liver dysfunction or myopathy, Dr. Poldermans reported.

The findings also raise the question of whether the results are a class effect for all statins or specific to fluvastatin XL because of its extended serum half-life.

Fluvastatin XL is not commonly prescribed in the United States, Dr. Gardner noted, although the drug has been available since its Food and Drug Administration approval in 2000.

Fluvastatin XL (Lescol XL) is marketed by Novartis. Dr. Poldermans's study, done entirely at Erasmus University, had no funding from Novartis. Dr. Poldermans reported receiving educational grants from Novartis as well as other drug companies.

"The risk profile of the treatment is so benign that we may need to consider changing the guidelines" for patients undergoing elective vascular surgery, commented Dr. Marc E. Shelton, who is the medical director of the Prairie Diagnostic Center at the Prairie Heart Institute in Springfield, Ill.