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Statins are Associated with a Reduced Incidence of Perioperative Mortality in Patients Undergoing Major Noncardiac Vascular Surgery

Poldermans D, Bax JJ, Kertai MD, Krenning B, Westerhout CM, Schinkel AFL, Thomson IR, Lansberg PJ, Fleisher LA, Klein J, van Urk H, Roelandt JRTC, Boersma E. Circulation 2003; 107:1848-1851

Reviewer: Mark A. Chaney, MD

Chicago, IL

Abstract Excerpt

Due to underlying coronary artery disease, patients undergoing major vascular surgery are at increased risk of perioperative mortality. Statins (inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A) may reduce perioperative mortality through the improvement of lipid profile, but also through the stabilization of coronary plaques on the vascular wall. These investigators evaluated the association between statin use and perioperative mortality by performing a case-controlled study among almost three thousand patients who underwent major vascular surgery at a single center. "Case subjects" (patients who died during their hospital stay following surgery) were compared with two "control subjects" selected and stratified according to calendar year and type of surgery. For cases and controls, information was obtained regarding statin use before surgery, the presence of cardiac risk factors, and the use of other cardiovascular medication. Statin therapy was significantly less common in patients who died than in patients who did not die (8% versus 25%; P < 0.001). The adjusted odds ratio for perioperative mortality among statin users as compared with nonusers was 0.22 (95% confidence interval 0.10 to 0.47). Similar results were obtained in subgroups of patients according to the use of cardiovascular therapy and the presence of cardiac risk factors. Thus, this retrospective case-controlled investigation provides evidence that statin use may reduce perioperative mortality in patients undergoing major vascular surgery.

Reviewer's Comments

Patients undergoing major vascular surgery experience high mortality (approximately 5% at thirty days), with myocardial infarction being the most common fatal complication. Although the understanding of the pathophysiology is not entirely clear, there is evidence that coronary plaque rupture, which leads to thrombus formation and subsequent vessel occlusion, is the dominant causative mechanism behind such complications, similar to myocardial infarctions occurring in the nonoperative setting. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (statins) may have a beneficial influence because of a direct effect on vascular function, which results in coronary plaque stabilization. These investigators examined the association between statin therapy and perioperative mortality in patients undergoing major vascular surgery. They undertook a retrospective case-controlled study among 2816 patients undergoing major vascular surgery between 1991 and 2000 in a single institution in the Netherlands. 160 patients (5.8%) died during surgery or during the first thirty postoperative days. For each of these patients, two control subjects were identified and stratified according to calendar year and type of surgery. Intense statistical analysis was performed on a wide variety of perioperative variables. Statin use was significantly less common in patients who died (8%) than in controls (25%). The risk of perioperative mortality among statin users was reduced 4.5 times compared with nonusers. Of note, beta-blocker therapy was also significantly less common in patients who died (19%) than in controls (36%) and the risk of perioperative mortality among beta-blocker users was reduced 2.3 times compared with nonusers.

Patients with peripheral vascular disease often have extensive coronary artery disease, characterized by the presence of asymptomatic but vulnerable atherosclerotic plaques, which may rupture because of the stress of surgery. Therefore, a systemic medical therapy for plaque stability is an attractive option. Statins may provide such systemic effect because of their antiinflammatory action and reversal of endothelial dysfunction. All of these factors may induce a shift from pro-thrombosis and vasospasm to more stable thrombo-resistant conditions and vasodilation, thereby reducing perioperative myocardial ischemia. Besides the beneficial effects of statins, this investigation also confirmed the cardioprotective effects of beta-blockers. Furthermore, the effect of statins on perioperative mortality was similar in beta-blocker users and nonusers. Thus, beta-blockers may beneficially influence myocardial supply/demand mismatch whereas statins may beneficially influence coronary plaque stabilization. Obviously, many limitations are present in any study relying on retrospective data collection. However, the results of this intriguing investigation suggest that preoperative statin therapy may be associated with a reduction in perioperative mortality. Although possible mechanisms of the potential beneficial effects of statins remains speculative, further large-scale, randomized clinical trials investigating early treatment with statins in such patients is strongly recommended.

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