Fluvastatin XL use is associated with improved cardiac outcome after major vascular surgery. Results from a randomized placebo controlled trial: DECREASE III.
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 Presenter report:
Poldermans, Don (Netherlands)
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Annually approximately 40 million people undergo noncardiac surgery in the European Union. Of these patients, approximately 400,000 (1%) will suffer a perioperative myocardial infarction (PMI) while approximately 133,000 (0.3%) die because of cardiac complications. In particular, in patients undergoing noncardiac vascular surgery, the incidence of perioperative cardiac complications is high, with cardiac mortality rates exceeding 2%. Indeed perioperative cardiac events are the major cause of adverse outcome in vascular surgery patients. |
Recent retrospective studies suggested a potential beneficial role of statins in the prevention of PMI, in particular by “stabilizing” coronary plaques due to their pleiotropic, anti-inflammatory effects.
Between June 2004 and April 2008, 497 statin-naive patients scheduled for vascular surgery were included in the trial at Erasmus MC Rotterdam, the Netherlands. Patients were randomized to receive either placebo or fluvastatin extended release at a dose of 80 mg once daily.
Myocardial ischemia was detected in 74 (14.9%) patients within 30 days of the initial vascular surgical procedure. A total of 27/250 (10.9%) patients allocated to fluvastatin reached the primary endpoint compared to 47/247 (18.9%) patients allocated to placebo treatment (OR 0.53; 95% CI 0.32-0.88). Hence, the number needed to treat (NNT) to prevent one patient experiencing myocardial ischemia was 12.5 patients. A total of 18 (3.6%) patients died within 30 days after surgery of which 12 (2.4%) were attributable to cardiovascular causes. Additionally, 25 (5.0%) patients experienced a nonfatal myocardial infarction within 30 days after surgery. The combined endpoint of cardiovascular death and nonfatal myocardial infarction was reached in 37/497 (7.4%) patients. A total of 12/250 (4.8%) patients allocated to fluvastatin therapy reached the combined endpoint, compared to 25/247 (10.1%) allocated to placebo. Hence, fluvastatin therapy was associated with a 52% relative reduction in the incidence of cardiovascular death or MI (OR 0.48; 95% CI 0.24-0.95). The NNT for the composite endpoint of cardiovascular death or nonfatal MI is 18.9 patients.
Conclusion:
Fluvastatin XL therapy was associated with improved postoperative cardiac outcome in high-risk patients undergoing elective vascular surgery.
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 Discussant report:
Shelton, Marc (United States of America)
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This study is clean, well thought out, clinically important, and academically interesting. I don't have anything of substance to quibble about concerning how it was run. In several previous studies of the perioperative use of statins in patients undergoing major peripheral procedures, there were signals that statin treated patients might have improved outcomes, but these studies were retrospective and observational in nature and hence potentially confounded by selection bias.
 Slides available
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The results in DECREASE III show significant reduction in myocardial ischemia and the combined endpoint of cardiovascular death and non-fatal myocardial infarction in patients treated with fluvastatin XL vs placebo before and after major vascular surgery. Like many good clinical studies, several academically interesting questions are raised:
First, one wonders if the beneficial effect noted in this study is unique to fluvastatin, or is a general effect of statins.
Second, is there a systemic inflammatory effect caused by cross-clamp injury or a hemodynamic injury or some combination of both and was this ameliorated by a pleiotropic effect of the fluvastatin? One wonders if there is a correlation between the amount of endothelial activation and clinical outcomes? Is there a difference in open vs percutaneous procedures?
Third, are there genetically determined differences in the patients? Are there "responders vs non-responders"?
Finally, are there clinically important "co-triggers" such as diabetes, obesity, smoking, sleep apnea, or platelet reactivity?
It also might be interesting to compare the fluvastatin group to outcomes in the excluded patients who were already on statins long-term to help address the question of whether the fluvastatin benefit was related to reduction in cholesterol pools vs a pleiotropic effect. Is there a correlation between statin intolerance and poor outcomes? How did the excluded patients fare?