In patients undergoing vascular surgery, peri-operative fluvastatin therapy was associated with an improvement in postoperative cardiac outcome, according to the DECREASE III trial published Sept. 3 in the New England Journal of Medicine.
In double-blind, placebo-controlled DECREASE (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography), the researchers sought to evaluate whether peri-operative statin therapy would improve postoperative outcomes.
Olaf Schouten, MD, PhD, from the Erasmus Medical Center in Rotterdam, the Netherlands, and colleagues randomly assigned patients who had not previously been treated with a statin to receive, in addition to a beta-blocker, either 80 mg of extended-release fluvastatin (Lescol from the Basel, Switzerland-based Novartis) or placebo once daily before undergoing vascular surgery. They measured lipid, interleukin-6 and C-reactive protein levels at the time of randomization and before surgery.
The authors wrote that the primary endpoint was the occurrence of myocardial ischemia, defined as transient electrocardiographic abnormalities, release of troponin T, or both, within 30 days after surgery. The secondary endpoint was the composite of death from cardiovascular causes and MI.
The researchers assigned 250 patients to fluvastatin and 247 to placebo, a median of 37 days before vascular surgery. Levels of total cholesterol, low-density lipoprotein cholesterol, interleukin-6 and C-reactive protein were “significantly decreased in the fluvastatin group but were unchanged in the placebo group,” they wrote.
Schouten and colleagues found that postoperative MI occurred in 10.8 percent of patients in the fluvastatin group and in 19 percent in the placebo group. Death from cardiovascular causes or MI occurred in 4.8 percent of patients in the fluvastatin group and 10.1 of patients in the placebo group. The researchers noted that fluvastatin therapy was not associated with a significant increase in the rate of adverse events.
One concern with peri-operative statin treatment is the necessity of treatment interruption when oral administration is not feasible during the early postoperative period, the authors said. “Such interruption is potentially hazardous, as sudden withdrawal of statins in the nonsurgical setting has been associated with a diminished benefit,” they wrote.
The present study found that fluvastatin had to be interrupted in approximately a quarter of the patients for a median of two days. However, when the analysis was corrected for baseline characteristics and type of surgery, Schouten and colleagues did not find a significant increase in the rate of adverse outcomes among patients in whom fluvastatin was interrupted as compared with those who continued to receive the drug. “These findings support the hypothesis that treatment with extended-release fluvastatin is robust to a gap in therapy of one to two days after surgery, when oral intake is not yet feasible,” the researchers concluded.
The study was supported by unrestricted research grants from Novartis, the Netherlands Organization for Health Research and Development, Erasmus Medical Center, Stichting Lijfen Leven and the Netherlands Heart Foundation.