News:Fluvastatin XL therapy may prevent adverse cardiac outcomes in patients undergoing major vascular surgery: Results from the DECREASE III trial

September 1, 2008 by Katherine Ogando [mailto:kogando@perfuse.org]

The DECREASE III trial enrolled 497 patients randomized to placebo or an 80 mg dose once daily of fluvastatin extended release (Novartis, Basel, Switzerland). The patients were not undergoing statin therapy and were scheduled to undergo vascular surgery at the time of inclusion. Treatment started at a median of 37 days prior to surgery and continued at least 30 days after surgery. Baseline inflammatory markers were assessed for both the placebo and fluvastatin group. Hs-CRP and IL-6 levels were significantly lower in the treatment group compared to placebo at the time of hospital admission (6.00 mg/L vs. 4.66 mg/L, p-0.030, and 8.45 pg/ml vs. 5.75 pg/ml, p=0.024, respectively).

All randomized patients were included in the primary analysis of intention-to-treat. 115 patients (23%) were discontinued from study treatment directly after surgery for a median of 2 days due to inability to administer the drug orally. 34 other patients were discontinued from the study medication because of abnormal lab results. In addition 16 patients (3.2%) were discontinued because of ALAT exceeding 3x the upper limit of normal, 13 patients (2.6%) discontinued due to CK exceeding 10x upper limit of normal, and 5 (1.0%) because of a combination of these two factors. Recruitment occurred at Erasmus MC Rotterdam, the Netherlands.

The primary endpoint of myocardial ischemia within 30 days of the initial vascular surgical procedure was identified in 74 patients (14.9%). 10.9 percent of fluvastatin patients (27/250) experienced this endpoint, compared to 18.9 percent (47/247) of patients in the placebo group (OR 0.53; 95% CI 0.32-0.88). The number needed to treat (NNT) was 12.5 patients.

The overall mortality within 30 days of the initial vascular procedure was 3.6% (18 patients), with 2.4% (12) of these due to cardiovascular causes. There were 25 cases (5.0%) of nonfatal MI, and 7.4% of patients (37/497) experienced a combined endpoint of cardiovascular death and nonfatal MI. Fluvastatin therapy was associated with a 52% relative reduction in the incidence of the secondary endpoint of cardiovascular death or MI as 4.8% (12/250) of patients in the fluvastatin group experienced the combined endpoint, compared to 10.1% (25/247) of placebo patients (OR 0.48; 95% CI 0.24-0.95). The NNT for the composite endpoint is 18.9 patients.

Both the fluvastatin group and the placebo group exhibited comparable shares of adverse events throughout trial duration. There was an increase in CK levels greater than 10 times the UL of normal of 4.1% vs. 3.0% in the fluvastatin group and placebo group, respectively. Similarly, median peak levels were 141 U/L vs. 113 U/L in fluvastatin vs. placebo, respectively (p=0.24). There was also an insignificant difference between both groups in increased ALAT levels of 3.1% in the fluvastatin group and 5.2% in the placebo group, with the median peak ALAT level at 23 U/L and 24 U/L in the fluvastatin group and placebo group, respectively.

The outcomes of the DECREASE III trial add to the recent findings of other retrospective studies that suggest a protective role of statins in the prevention of perioperative myocardial infarction (PMI). In patients undergoing elective vascular surgery, PMI and cardiac complications arising from PMI have been shown to be a significant cause of adverse outcomes. These results suggest the added value of fluvastatin XL therapy in improved outcomes for high risk patients undergoing vascular surgery.