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ROTTERDAM, The Netherlands, May 8 — High dose corticosteroid therapy may increase the risk of atrial fibrillation, researchers here reported.

A daily dose of at least 7.5 mg of prednisone equivalents was associated with a six-fold increase in risk of new onset atrial fibrillation, Cornelis S. van der Hooft, M.D., and colleagues, of Erasmus University Medical Center reported in the May 9 issue of the Archives of Internal Medicine.

Moreover, the increased risk was "found in patients with and without asthma/COPD", the authors wrote.

There was, however, no observed increase in the risk of atrial fibrillation among patients treated with low or intermediate doses of corticosteroids.

These data emerged from a nested case-control study within the Rotterdam Study, an ongoing population-based cohort study of 7,893 residents of Ommoord, a Rotterdam suburb.

All participants were 55 or older at baseline in 1990. Participants underwent follow-up examinations every four to five years. Corticosteroid use was tracked by computerized pharmacy records. The study endpoint was atrial fibrillation, death, or the end of the study period, which was Jan. 1, 2000).

During the follow-up the researchers identified 385 patients with new onset atrial fibrillation, which were included in the analysis. Those cases were compared with 6,365 controls.

High-dose corticosteroid use was associated with an odds ratio of 6.07 for atrial fibrillation (95% CI, 3.90-9.42) whereas low-intermediate-dose use was not (OR, 1.42; 95% CI, 0.72-2.82).

Because patients taking high-dose corticosteroids had other risk factors for atrial fibrillation, the authors performed two additional analyses.

"In an age-and sex-adjusted analysis including the sum score as a continuous variable, the measures of association became stronger," they found. "For the high-dose group, the OR became 6.43 (95% CI, 4.38-9.45), while it was 6.07 (95% CI, 3.90-9.42) in the multivariate analysis. For the high-dose asthma/COPD group, the OR became 4.33 (95% CI, 2.27-8.27), while it was 4.02 (95% CI, 2.07-7.81) in the multivariate analysis. For the high dose in other disease group, the OR became 9.88 (95% CI, 5.72-17.07), while it was 7.90 (95% CI, 4.47-13.98) in the multivariate analysis."

They then divided the cases into two groups--those with zero to two risk factors for atrial fibrillation and those with three or more risk factors. Then they analyzed the data again. Using that risk stratified model, they found that among patients with zero to two risk factors who took high-dose corticosteroids the OR was 7.09 (95% CI, 3.62-13.90), while in those with three or more atrial fibrillation risk factors the OR was 6.09 (95% CI, 3.81-9.76).

The study findings triggered an immediate response from the American Heart Association, which issued a statement warning that patients taking corticosteroids should "not immediately stop taking them," said Kenneth Ellenbogen, M.D., an AHA spokesperson, of the Virginia Commonwealth University in Richmond. He warned that abrupt cessation of corticosteroid therapy can trigger adrenal crisis.

That said, Dr. Ellenbogen said the Dutch study was important because corticosteroids are first-line therapy for many conditions, including asthma/COPD as well as rheumatoid arthritis. "The results of this study now provide physicians with an added tool to balance the benefit to risk ratio as to which patients these medications are best for," he said. "Prescribing them remains an individual decision between each patient and doctor."

Dr. van der Hooft and colleagues concluded that patients on high-dose corticosteroid therapy should be closely monitored with both clinical examination and ECG before and after high-dose (pulse) therapy. Such monitoring, they wrote, "could increase the chance to diagnose and treat this serious arrhythmia as early as possible."

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