Statins May Aid in Carotid Endarterectomy

WASHINGTON -- Perioperative statin use may reduce significantly the incidence of cerebrovascular events and mortality among patients undergoing carotid endarterectomy, Dr. Bruce A. Perler, reported at a conference for science reporters sponsored by the American Medical Association.

Dr. Perler and his associates conducted a retrospective analysis of 1,566 patients who underwent carotid endarterectomy (CEA) between 1994 and 2004 at Johns Hopkins Hospital. Those who had been taking a statin for at least 1 week prior to the procedure had a threefold reduction in stroke and fivefold reduction in death in the subsequent 30 days, compared with those not on a perioperative statin. The effects were independent of other risk factors, and both were highly significant.

"The results were quite remarkable to us, really eye-opening," said Dr. Perler, professor and chief of vascular surgery at Johns Hopkins University, Baltimore.

"Because this was a retrospective study and not designed to establish clinical practice, I can't make a blanket statement based on this research that everybody ought to be on a statin before they have a carotid endarterectomy. But one can certainly speculate that it's a reasonable thing to do," Dr. Perler said.

Results of the study, which was not industry funded, were published in November (J. Vasc. Surg. 2005;42:829-36).

Of the 1,566 patients, 92% underwent solitary CEA; the other 8% had simultaneous coronary artery bypass grafting (CABG). Mean age was 72 years, and 63% were male.

Indications for CEA were symptomatic disease in 42% (14% with a history of stroke and 28% with transient ischemic attacks) and asymptomatic stenosis in 58%.

A total of 42% of the patients had been using statins for at least 1 week prior to the procedure. The most commonly used statins were atorvastatin (51%) and simvastatin (29%), both at a mean dose of 20 mg/day.

Although the duration of statin therapy was unknown, most of the patients had been taking them for quite a bit longer, Dr. Perler noted.

At 30 days after CEA, the incidence of stroke among the 657 statin users was 1.2%, compared with 4.5% of the 909 not on statins. Mortality among patients on statins was just 0.3% versus 2.1% in patients not taking the agent.

Perioperative myocardial infarctions were also less frequent among the statin users (1.2% vs. 2.1%), but that difference did not reach statistical significance. Although overall statin use increased with time over the 10-year period, the protective effect is not due to the increase in people taking these agents from 10 years ago. The differences between statin users and nonusers remained significant throughout, he said.

After adjustment for all comorbidities found to be associated with stroke (presence of symptomatic carotid disease, chronic atrial fibrillation, hyperlipidemia, use of intraluminal shunt and patch grafting, and combined CEA/ CABG), statin use remained associated with a threefold reduction in the 30-day risk for stroke (odds ratio 0.29).

Similarly, after adjustment for the other factors that predicted perioperative mortality (percent carotid stenosis, hypertension, chronic atrial fibrillation, coronary artery disease, heart failure, chronic renal insufficiency, use of ?-blockers, and combined CEA/CABG), statin use was still associated with a fivefold reduction in death (OR 0.21).

Other factors that also remained independently associated with an increased risk of mortality were chronic atrial fibrillation, chronic renal insufficiency, and combined CEA/CABG, while use of ?-blockers remained predictive of a lower risk for death.

Although this study is the first ever to investigate the impact of statin use on CEA outcome, there have been several previous clinical trials supporting the use of statin therapy to reduce complications after other vascular procedures, including CABG (Circulation 2000;110[suppl. 2]: 1145-9 and Am. J. Cardiol. 2000;86:1128-30).

The fact that statins have been shown to reduce the risk of stroke in individuals with both normal and elevated cholesterol levels--and that the same effect has not been seen with nonstatin cholesterol-lowering agents--suggests that the mechanism is related to the statins' non-lipid-mediated actions.

These include stabilization of atherosclerotic plaques and improvement of endothelial function, along with antithrombotic, anti-inflammatory, and antioxidant effects.

"Statins have all these effects at the cellular level. They're not just for lowering cholesterol," Dr. Perler remarked.

Given their plaque-stabilizing potential, it would be reasonable to assume statins would have a similar protective effect as adjunctive therapy for patients undergoing carotid angioplasty and stenting, as well.

"It certainly ought to be considered--although that's pure speculation, because our study didn't address that," Dr. Perler said in responding to a reporter's question.

But what this study does point to, he noted, is a potential way to enhance the safety of CEA, the most commonly performed of all noncardiac vascular procedures.

Although still considered the "gold standard" for treating occlusive carotid disease, that status is now being challenged by data suggesting that the minimally invasive alternative of carotid stenting is not inferior with regard to outcomes (N. Engl. J. Med. 2004;351:1493-501).

But if these retrospective data are confirmed by prospective studies--which would also need to establish the minimal duration of statin use and dose needed to be effective--CEA could retain the upper hand. CEA "is a great operation and a safe operation. We're very excited about data we think will make a safe operation even safer," he said.