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Lung Cancer: Amiodarone Prevents Atrial Fibrillation after Surgery; Statin Also Shows Promise

Laino, Charlene

doi: 10.1097/01.COT.0000413200.46728.4c
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FORT LAUDERDALE—Postoperative administration of the antiarrhythmic agent amiodarone after lung cancer resection surgery significantly diminishes the occurrence of atrial fibrillation, according to results of a controlled, randomized, double-blind trial reported here at the Society of Thoracic Surgeons Annual Meeting.

The study, the J. Maxwell Chamberlain Memorial Paper for General Thoracic Surgery, was presented by Lars P. Riber, MD, PhD, consultant physician in the Department of Cardiothoracic and Vascular Surgery at Aarhus University Hospital in Denmark.

The study included 242 patients undergoing lobectomy, 11 of whom (9%) who received amiodarone had atrial fibrillation versus 38 (32%) who received placebo. This corresponds to a significant, 71% reduction in relative risk with use of the antiarrhythmic drug, he said.

Also at the meeting, researchers reported preliminary data showing that preoperative treatment with atorvastatin reduced postoperative atrial fibrillation by 44%. However, the trend did not achieve significance, probably due to a small sample size, said David Amar, MD, Director of Thoracic Anesthesia at Memorial Sloan-Kettering Cancer Center.

Atrial fibrillation is “not uncommon” among patients undergoing lung cancer resection surgery, with a rate of 30% most often quoted, according to the study's Discussant, Kemp H. Kernstine, MD, PhD, Chairman of Thoracic Surgery at the University of Texas Southwestern Medical Center.

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Patients who develop atrial fibrillation are at greater risk for stroke, myocardial infarction, and other acute morbidities related to hemodynamic instability, and postoperative atrial fibrillation is the second most common reason for delay of discharge from the hospital. In the Danish study, the typical patient spent about two days in the intensive care unit and nearly another five days on the ward, whereas in academic or high-volume institutions, the stay might be no more than five days, he noted.

“Many medical oncologists don't think atrial fib is a big deal, but I stress its importance. There are a number of patients who go into chronic afib and do not come out and then have to be on warfarin, with a lot of associated morbidity. It can complicate giving adjuvant chemotherapy and care if a patient is on warfarin.”

Riber noted that amiodarone has been shown to be effective for the management of atrial fibrillation not related to surgery. It has also been widely studied for the prevention of atrial fibrillation after cardiac surgery, but its role after noncardiac thoracic surgery is less well defined.

Kernstine cited a prospective trial in 1994 that was terminated after amiodarone was associated with an increase in pulmonary adverse events (Van Mieghem et al:Chest 1994;105:1642-1645). However, he added, in a 2009 study, amiodarone prophylaxis significantly reduced the incidence of atrial fibrillation after anatomic pulmonary resection and was associated with a significant reduction in the length of stay in the intensive care unit (Tisdale et al:Ann Thorac Surg 2009;88:886-895).

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Study Details

In the new study, 122 patients were given a 300-mg intravenous bolus infusion of amiodarone and 120 were given placebo, administered over 20 minutes shortly after transfer to the ICU. Patients were then given 600 mg of oral amiodarone or placebo twice a day, at 8 am and 6 pm, for the first five postoperative days.

Patients also received standard-of-care medications. Thirty-three patients received preoperative treatment with a beta blocker, 17 patients in the amiodarone arm and 16 in the placebo arm. Beta blockers can have an additive effect in preventing atrial fibrillation, Riber said.

Prophylactic use of amiodarone was not associated with an improvement in mortality rates or length of stay, but that could be due to the study being underpowered—that is, too few patients and too short a follow-up period, he said.

Adverse events were observed in 10 patients, and were equally distributed between the two arms, he noted. “Serious adverse events could therefore not be related to the prophylactic regime in this study.”

Unlike in the 1994 study, there was no increase in pulmonary complications with amiodarone. In the 2009 study that did show a benefit for amiodarone, the treatment group received 1,050 mg of amiodarone by continuous intravenous infusion over 24 hours, initiated at the time of anesthesia induction, followed by 400 mg orally twice daily until hospital discharge or for a maximum of six days.

“The importance of the current study is it used a lower [IV] dose and still there was over a 70% relative risk reduction in atrial fibrillation with amiodarone. That's huge, a dramatic improvement in the care of patients,” he said. “Amiodarone should be used routinely in this setting,” he said.

Riber said that while his team has shown that the prophylactic use of amiodarone in bypass surgery patients is cost-effective, it has yet to be studied in the setting of lobectomy.

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Statin Treatment

In the statin late-breaking study, Amar said that postoperative atrial fibrillation has been linked to inflammatory and oxidative mechanisms and that his team has previously shown that chronic statin therapy reduces postoperative atrial -fibrillation after thoracic surgery (Chest 2005;128:3421-3427).

The new interim analysis involved 87 patients without previous statin treatment undergoing major anatomic lung resection. Half received 40 mg/day of atorvastatin and the rest received placebo, starting seven days before and continued for seven days after surgery.

DAVID AMAR, MD: “Preoperative treatment with atorvastatin reduced postoperative atrial fibrillation by 44%

DAVID AMAR, MD: “Preoperative treatment with atorvastatin reduced postoperative atrial fibrillation by 44%

Postoperative atrial fibrillation occurred in six of 43 patients (14%) in the ator-vastatin arm versus 11 of 44 (25%) in the placebo arm. This corresponded to a 44% reduction in postoperative atrial fibrillation in patients taking the statin, but did not achieve significance, Amar said.

One week of atorvastatin pretreatment also did not lower systemic inflammatory markers. “It is likely local tissue inflammatory and oxidative mechanisms and not systemic inflammation that contributes to postoperative atrial fibrillation.”

He said he hopes to see the difference in postoperative atrial fibrillation rates reach significance once all patients are analyzed. He and his co-researchers hypothesized that a sample size of 276 patients is needed to reduce postoperative atrial fibrillation from 27% to 13%, with 80% power.

“The mechanism by which atorvastatin may prevent postoperative atrial fibrillation also requires further study,” he said.

And in response to questions from the audience, he said that only clinically significant cases of atrial fibrillation that required treatment were picked up and that use of steroids was not allowed.

© 2012 Lippincott Williams & Wilkins, Inc.
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