Nov 11 2008
Giving interferon to heart failure patients with evidence of a chronic viral infection safely eliminated two viruses from their systems and reduced levels of a third virus.
Additionally, there were trends toward improved cardiac function and quality of life, but these did not reach significance at 24 weeks, researchers reported at the American Heart Association's Scientific Sessions 2008. Results from the Effect of Subcutaneous Treatment with Interferon-Beta-1b over 24 weeks on Safety, Virus Elimination and Clinical Outcome in Patients with Chronic Viral Cardiomyopathy study were presented as a late-breaking clinical trial.
"These results from our randomized trial provide the first evidence that interferon beta-1b (IFNB-1b) treatment eliminates cardiotropic viruses and may improve the clinical outcomes of patients with chronic enteroviral and adenoviral heart disease," said Heinz Peter Schultheiss, M.D., the lead author of the study and a professor of medicine in the Department of Cardiology and Pneumology at Charite - University Medicine of Berlin, Campus Benjamin Franklin in Berlin, Germany.
The double-blind Phase II study included 143 patients at 31 medical centers in seven European countries.
Investigators also found a reduction in the viral load for parvovirus, but not evidence for elimination.
Researchers found that patients infected with adenovirus, enterovirus and/or parvovirus B19 who received IFNB-1b were about twice as likely to have improved symptoms 12 weeks after treatment ended. They found that 38.6 percent of the interferon patients had an improved New York Heart Association (NYHA) functional classification as compared to 18.6 percent of those in the placebo group at 12 weeks. However, by the 24th week, the placebo group had improved slightly and the difference between groups was not statistically significant.
The quality of life score, as measured by the Minnesota Living with Heart Failure Questionnaire, improved continuously during treatment, and was more pronounced in the enterovirus/adenovirus subgroup than in the subgroup with parvovirus. Those findings also fell short of statistical significance when compared with placebo.
Researchers reported no safety issues. The study tested two different dosages of interferon. Because both dosages appeared equally effective in viral elimination, the researchers combined the results for both interferon groups into one group for comparison with the placebo group.
The 143 patients randomized to interferon or placebo all had chronic heart failure and the presence of one of three viruses -- adenovirus, enterovirus and parvovirus B19 -- as shown by specimens obtained by heart biopsy. A total of 131 patients completed the study, which required a second heart biopsy to determine viral load after treatment.
The researchers divided the participants into one of three treatment arms: the first two groups got one of two doses of interferon and the third received a placebo, an inactive medication indistinguishable from the interventional drug given subcutaneously (under the skin) every other day for 24 weeks.
The primary endpoint was the absence of adenovirus, enterovirus and parvovirus in biopsies taken an average of 12 weeks after treatment ended. For the parvovirus group, virus elimination was assessed with a quantitative assay. Schultheiss said IFNB-1b resulted in clearance of all enteroviruses and adenoviruses, but noted that parvovirus persisted in some of the double infected patients.
According to the definition of the primary endpoint, only patients with complete clearance of both viruses were calculated as responders. This resulted in clearance rates of 40 percent and 50 percent in the chronic adenovirus-enterovirus group, depending on the dose, and clearance or reduction rates of 31.8 percent to 35.7 percent in the parvovirus group, Schultheiss said.
Secondary endpoints included change in NYHA functional class; performance on a six-minute walk test; individual clinical symptoms; quality of life and echocardiographic left ventricular ejection fraction (LVEF) -- a measure of the heart's ability to pump blood -- both at rest and on exertion; and several other measures of heart function and inflammation. No significant changes in these were reported at 24 weeks after treatment, although there were trends toward improvement.
Co-authors are: Cornelia Piper, M.D., Ph.D.; Olaf Sowade, M.D.; Kristjan Karason, M.D., Ph.D.; Joachim-Friedrich Kapp, M.D., Ph.D.; Karl Wegscheider, Ph.D., M.Sc.; Georg Groetzbach, M.D.; Finn Waagstein, M.D., Ph.D.; Eloisa Arbustini, M.D.; Harald Siedentop, Ph.D.; and Uwe Kuehl, M.D., Ph.D. Individual author disclosures can be found on the abstract.
The study was funded by Bayer Health Care.
Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The association makes no representation or warranty as to their accuracy or reliability. The association receives funding primarily from individuals; foundations and corporations (including pharmaceutical, device manufacturers and other companies) also make donations and fund specific association programs and events. The association has strict policies to prevent these relationships from influencing the science content. Revenues from pharmaceutical and device corporations are available at http://www.americanheart.org/corporatefunding.
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