Increased warfarin requirements in a patient with chronic hepatitis C infection receiving sofosbuvir and ribavirin.

PURPOSE: A case of increased warfarin requirements during treatment with sofosbuvir and ribavirin for chronic hepatitis C virus (HCV) infection is reported. SUMMARY: A 63-year-old white man receiving long-term anticoagulation with warfarin for atrial fibrillation and a history of cardioembolic stroke was initiated in September 2014 on a 12-week course of sofosbuvir 400 mg orally daily and weight-based ribavirin 600 mg orally twice daily for HCV genotype 2 infection. Before starting this treatment regimen, the patient had been stable on warfarin 52.5 mg weekly, with therapeutic International Normalized Ratio (INR) values. During the 12-week course of sofosbuvir and ribavirin, the patient's dose of warfarin progressively increased from 52.5 to 77.5 mg weekly due to subtherapeutic INRs, with the first adjustment in the warfarin dose occurring 9 days after initiation of HCV treatment. Three weeks after completion of the sofosbuvir and ribavirin regimen, the patient's INR was 3.06, and his warfarin dose was then decreased to 70 mg weekly. The patient continued with this warfarin dosage until 18 weeks after completion of his HCV regimen. The dosage was then decreased to 65 mg weekly after an INR of 3.86. Three weeks later, his INR was 2.19, and warfarin 65 mg weekly was continued. As of June 2016, the patient has continued to require warfarin 62.5-65 mg weekly to maintain a therapeutic INR. CONCLUSION: A 63-year-old man on a stable dose of warfarin experienced a decrease in INR values after the initiation of a 12-week course of sofosbuvir and ribavirin for the treatment of chronic HCV infection.

Double dose vs. standard dose influenza vaccination in patients with heart failure: a pilot study.

AIMS: Influenza infection leads to increased morbidity and mortality in those with heart failure, and individuals with heart failure exhibit reduced antibody responses to influenza vaccine. We hypothesized that patients with heart failure randomized to double dose (DD) influenza vaccine will mount more vigorous humoral immune responses compared with those given standard dose (SD) vaccine. METHODS AND RESULTS: We randomized 28 heart failure patients to DD (30 µg/strain) or SD (15 µg/strain) influenza vaccine. We assessed antibody production by haemagglutination inhibition assay (reported as log haemagglutination units) prior to, at 2-4 weeks and at 4-6 months following vaccination. Baseline antibody titres between DD (n = 12, mean age 64 ± 10 years) and SD (n = 16, mean age 63 ± 9 years) did not differ significantly. At 2-4 weeks, DD haemagglutination unit changes were significantly higher than those of SD (3.3 vs. 1.6 for A/H3N2, P < 0.001; 1.9 and 1.1 for A/H1N1, P = 0.009; and 1.7 and 1 for B-type, P = 0.02). At 4-6 weeks, there were no differences in titres in any of the virus types between treatment groups and, although titres decreased, levels remained above the seroprotective threshold. CONCLUSIONS: Higher influenza vaccine doses may elicit increased antibody-mediated responses in patients with heart failure; further studies should assess whether clinical outcomes are improved with this strategy.