Arrhythmias During Pegylated Interferon Alfa-2b (Peg-Intron) and Ribavirin Therapy: Observations from the WIN-R Trial

Interferon has been associated with cardiac arrhythmias. Ribavirin (RBV) causes a dose-dependent hemolytic anemia that may exacerbate underlying cardiac disease.

The objective of the present study was to assess the frequency and clinical presentation of arrhythmias occurring during hepatitis C (HCV) therapy with pegylated interferon (PEGIFN) and RBV.

Using data from the WIN-R Trial, a US multi-center study comparing fixed (800 mg) vs. weight based (800-1400 mg) RBV dosing with peginterferon alfa-2b (Peg-Intron) 1.5 mcg/kg/week, researchers identified patients with arrhythmias reported as serious adverse events (SAE).

Results

4900 patients received at least 1 dose of PEGIFN and RBV. Nine patients had arrhythmias occurring between 2 and 48 weeks of therapy (1 patient was at followup week 2): atrial fibrillation 6, multi-focal atrial tachycardia 1, atrial flutter 1, non-sustained ventricular tachycardia and SVT 1.

Four patients were male, all were Caucasian (mean age 57). Six patients started therapy on 1000-1200 mg of RBV; 3 started on 800 mg. Two patients had RBV dose reduction before the SAE.

Five patients had a prior history of cardiac disease (atrial fibrillation 2, 1st degree AV block 2, surgery to repair Tetrology of Fallot 1).

Based on TSH levels, 8 patients were euthyroid and 1 who developed atrial fibrillation was hyperthyroid.

The mean hemoglobin (Hb) at the time of the SAE was 12.5 gm/dl (n=8). Compared with baseline Hb, there was a mean decrease of 2.7 gm/dl at the time of the SAE. One patient with a history of alcohol abuse was newly diagnosed with cardiomyopathy with an ejection fraction of 20%.

Five patients were treated with medications, 2 were treated with medications and electrical cardioversion, the arrhythmia spontaneously resolved in 1, and the treatment data are not available for 1.

Anti-HCV therapy was discontinued in 3 patients, continued in 2, held for 2 weeks in 1, and therapy was dose reduced in 1.

In 1 patient the SAE was at treatment week 48 and 1 had completed therapy 2 weeks before the SAE.

Conclusions

(1)     Arrhythmias reported as SAEs occurred at a frequency of 0.2% during PEGIFN and RBV therapy in this study;

(2)     Approximately half of patients with arrhythmias during anti-HCV therapy had a history of conduction abnormalities or atrial fibrillation;

(3)     Arrhythmias were not related to severe anemia (Hb <10) in this series; and

(4)     Although one patient with atrial fibrillation had PEGIFN-induced hyperthyroidism, hyperthyroidism does not appear to be the cause of arrhythmias in the majority of these patients.

06/07/04

Reference
F Ahmed and others. Arrhythmias During Pegylated Interferon and Ribavirin Therapy for Chronic Hepatitis C: Observations from the WIN-R Trial. Abstract 1226 (poster). Digestive Disease Week. May 15-20, 2004. New Orleans, LA.