Giving Novartis’ long-acting cholesterol reducer Lescol XR (fluvastatin sodium extended-release tablets) to people undergoing blood vessel surgery can significantly reduce their risk of cardiac complications after the operation, a Dutch study suggests.

The results of the DECREASE (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography) III study, which Novartis said was the largest randomised, double-blind, placebo-controlled statin study in high-risk patients undergoing vascular surgery to date, were published in the 3 September issue of the New England Journal of Medicine.

As the study’s lead author, Professor Don Poldermans of the Erasmus Medical Centre in Rotterdam, pointed out, perioperative cardiac events are the major cause of adverse outcomes in high-risk vascular surgery patients, “and we need to make greater efforts to reduce them”.

The trial, which ran from June 2004 to April 2008 and was partially funded by Novartis, involved 497 patients scheduled for elective non-cardiac vascular surgery, including abdominal aortic aneurysm repair, distal aortoiliac reconstruction, lower-limb arterial reconstruction and carotid-artery endarterectomy.

The participants, who had not previously received statin treatment, were randomised to either Lescol XL 80mg daily and a beta-blocker (250 patients) or to placebo and a beta-blocker (247). Treatment was started a median of 37 days before surgery and was continued for 30 days after the procedure.

The primary endpoint was occurrence of myocardial ischaemia, defined as transient electrocardiographic abnormalities, release of troponin T or both, within 30 days of surgery. The secondary endpoint was a composite of death from cardiovascular causes and myocardial infarction.

The results showed that 27 (10.8%) of the patients given Lescol XL developed myocardial infarction within 30 days of the initial surgical procedure, compared with 47 (19.0%) of patients on placebo. This amounted to a 45% risk reduction with Lescol XL versus placebo.

Over the same time period, 12 or 4.8% of the patients treated with Lescol XL either died from cardiovascular causes or had a non-fatal myocardial infarction, compared with 25 or 10.1% of patients on placebo – a risk reduction of 53%. There were no significant differences in adverse events between Lescol XL and placebo, the researchers reported.

According to Novartis, some seven million adults in Europe undergo major non-cardiac surgery each year. It is estimated that 150,000 to 250,000 (2.0%-3.5%) of these patients will suffer a major cardiac complication. The risk of perioperative cardiac complications is particularly high, with a more than 5% chance of myocardial infarction or cardiac death, the company noted.

Professor Poldermans suggested that the improved cardiac outcomes seen with Lescol XL in the DECREASE III study might be at least partly due to non-lipid or pleiotropic and anti-inflammatory statin effects preventing plaque rupture and subsequent myocardial infarction during the perioperative period.

He said the study was the first to demonstrate conclusively that a statin could improve post-operative cardiac outcomes in vascular surgery patients. It also supported the Class I recommendation in new guidelines from the European Society of Cardiology that doctors should initiate and perioperatively treat high-risk non-cardiac surgery patients with a statin, Poldermans added.