Corticosteroids Stem Atrial Fibrillation After Cardiac Surgery

KUOPIO, Finland, April 10 -- Intravenous hydrocortisone after cardiac surgery had a 37% lower relative risk of post-op atrial fibrillation compared with placebo, researchers here reported.

The rate of atrial fibrillation after cardiac surgery, with its increased likelihood of stroke, fell from 48% to 30%, a reduced relative risk of 37%, when 241 patients were randomized to receive 100-mg hydrocortisone or matching placebo on the evening of the operative day, and then one dose every eight hours for three days.

Afib occurrence generally ranges from 20% to 40% after a coronary artery bypass graft and is even higher after valve and combined valve and bypass surgery, Jari Halonen, M.D., of Kuopio University Hospital, and colleagues reported in the April 11 issue of Journal of the American Medical Association.

The findings emerged from a double-blind, placebo-controlled, randomized multicenter trial at three university hospitals in Finland, with patients enrolled from August 2005 to June 2006.

The study included 241 consecutive patients without prior afib or flutter and scheduled to undergo a first on-pump CABG, aortic valve replacement, or combined CABG and valve replacement.

In addition to the hydrocortisone or matching placebo, patients received oral metoprolol (50 to 150 mg/d) titrated to heart rate.

The occurrence of post-op afib during the first 84 hours after surgery was significantly lower in the hydrocortisone group (36/120 [30%] versus 58/121 [48%]; adjusted hazard ratio, 0.54; 95% CI, 0.36-0.82, P<.01, the number needed to treat 5.6). The relative risk reduction was 37%.

The rate of in-hospital afib was also significantly lower in the hydrocortisone group (risk ratio, 0.74, CI, 0.56-0.97, P=.02).

One patient in the hydrocortisone group died of cardiac failure during the study period, and one placebo patient died on the ninth post-op day of multiorgan failure.

Compared with the placebo patients, the steroid patients did not have higher rates of post-op infections or other complications such as mediastinitis, stroke, myocardial infarction, conduction disturbances, or re-sternotomy caused by bleeding. Also, no psychotic disorders occurred in either group.

After adjusting for a variety of confounding factors, such as age, sex, left-ventricular ejection fraction, type of operation, unstable angina, chronic obstructive pulmonary disease, the treatment remained a significant independent predictor of lack of post-op afib, the researchers reported.

The researchers also noted that a meta-analysis that combined results of this trial with two other similar trials and included a total of 621 patients confirmed the beneficial effect of corticosteroid treatment over placebo for this use.

The method by which corticosteroids prevent postoperative afib is not entirely clear, although reducing a high inflammatory response may be partly responsible, the researchers suggested.

Markers of increased inflammatory reaction are higher in patients with post-op afib, and corticosteroids have anti-inflammatory activity. Concentrations of C-reactive protein were significantly lower in patients given steroid therapy, they said.

In addition, they wrote, the drugs reduced post-operative nausea, vomiting, and anorexia, possibly improving the absorption of oral medications, such as beta-blockers.

An important limitation of the study, the researchers noted, was that although IV hydrocortisone therapy was well tolerated, the study was underpowered to assess the safety of corticosteroid therapy, and a much larger trial is needed to demonstrate the noninferiority of corticosteroid treatment compared with placebo.

Another important limitation, they pointed out, is that patients having mitral valve surgery were excluded.

Earlier studies have reported that IV metoprolol, amiodarone, bi-atrial pacing, and magnesium reduce afib after cardiac surgery, the researchers said. Thus further studies are needed, they added, to clarify whether combining corticosteroids with other preventive measures would further reduce the afib risk.

"We conclude that intravenous administration of hydrocortisone is efficacious and well tolerated in the prevention of atrial fibrillation after cardiac surgery," Dr. Halonen wrote. "Larger trials will be needed to confirm our findings and determine short- and long-term safety of corticosteroids to prevent postoperative atrial fibrillation and other arrhythmias."