ESC: Statin Therapy Reduces Perioperative Cardiac Events

By Ed Susman
MUNICH, 07 sept 2008-- Extended-release fluvastatin (Lescol) -- given to patients just before undergoing vascular surgery and continued for a month -- reduced the relative risk of suffering a heart attack by a significant 47%, Dutch researchers reported here. "Perioperative extended-release fluvastatin use might be recommended in vascular surgery patients," suggested Don Poldermans, M.D., of Erasmus University in Rotterdam, at the European Society of Cardiology meeting. Treatment was started at the outpatient clinic on the day of randomization, a median 37 days prior to the surgical procedure, and was continued at least during the first 30 days after surgery. The primary analysis was intention-to-treat and involved all patients who were randomly assigned to either fluvastatin or placebo. Directly after surgery, study treatment was temporarily discontinued in 115 (23%) patients for a median duration of two days because of the inability to take the study drug orally.
A total of 34 patients discontinued the study medication because of laboratory abnormalities, 16 (3.2%) because of alanine aminotransferase exceeding three times the upper limit of normal, 13 (2.6%) because of creatinine kinase exceeding 10 times theupper limit of normal, and five (1%) because of a combination of elevated alanine aminotransferase and CK.
Dr. Poldermans said that myocardial ischemia occurred in 10.6% of the 250 patients assigned to fluvastatin compared with 18.2% of the 247 patients who were randomly assigned to receive placebo in the study (OR 0.53, 95% CI 0.32 to 0.88, P=0.016). The number needed to treat to prevent one patient experiencing myocardial ischemia was 12.5 patients.
In addition, he said that after 30 days of the trial period, 12 (4.8%) of the patients on fluvastatin achieved the secondary endpoint of cardiovascular death and/or nonfatal myocardial infarction compared with 25 (10.1%) of patients on placebo (OR 0.48, 95% CI 0.24 to 0.95, P=0.039).
In reporting the results of the Dutch Echographic Cardiac Risk Evaluating Applying Stress Echo III (DECREASE) trial, Dr. Poldermans noted that the use of 80 mg of extended-release fluvastatin in the patients just prior to surgery and until 30 days after the vascular surgery was not accompanied by an increase in adverse side effects, liver dysfunction, or myopathy compared with placebo.
"This therapy was associated with improved postoperative cardiac outcome in high-risk patients undergoing elective vascular surgery," he said.
"The results of DECREASE are a good demonstration of the benefits of statins beyond their ability to reduce cholesterol," commented Timothy Gardner, M.D., director of the Heart and Valvular Institute for Christiana Care, Wilmington, Del., and president of the American Heart Association. He said the patients were undergoing aortic surgery or peripheral vascular surgery.
Dr. Gardner said fluvastatin is not used widely in the United States so he anticipated that other companies that make statins were likely to attempt to replicate the results of DECREASE.
Dr. Poldermans said his group employed fluvastatin in the trial not to reduce cholesterol, but to make use of the purported pleiotropic effects of statins -- in particular the drugs' known ability to reduce inflammatory responses that occur in surgical scenarios.
He noted that about 2% of patients undergoing noncardiac vascular surgery die from cardiac causes during the perioperative period. He said that causes of perioperative myocardial infarction are complex but one theory suggests that coronary plaque instability leading to plaque rupture and thrombosis is a significant problem. He said the trial aimed at assessing the cardioprotective effect of fluvastatin on top of beta-blocker therapy in vascular surgery patients.
"What we have learned from the DECREASE study," said Elliot Antman, M.D., of Harvard Medical School, Boston, and another spokesperson for the American Heart Association, "is that there may be additional medical benefits of starting the statins early."
Neither Dr. Gardner nor Dr. Poldermans had any disclosures. Dr. Antman disclosed relationships with Merck & Co., Inc., Bristol-Myers Squibb Pharmaceutical Research Institute, sanofi-aventis, Millennium Pharmaceuticals, Nuvelo Inc., AstraZenaca Pharmaceuticals LP, CV Therapeutics, Inotek Pharmaceuticals Corporation, Eli Lilly and Company, Schering-Plough Research Institute, Integrated Therapeutics Corporation, Bayer Healthcare LLC, Ortho-Clinical Diagnostics, Inc., Sanofi-Synthelabo Recherche, GlaxoSmithKline, Amgen Inc., Beckman Coulter, Inc., Biosite Incorporated, Roche Diagnostics Corporation, Roche Diagnostics GmbH, Pfizer, Inc., Accumetrics, Inc., the National Institutes of Health, and Novartis Pharmaceuticals.
Primary source: European Society of CardiologySource reference:Poldermans D, et al "Fluvastatin XL use is associated with improved cardiac outcome after major vascular surgery: Results form a randomizxed placebo controlled trial" ESC 2008.