Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation : a randomised, open-label, non-inferiority trial

Background: Vitamin K antagonists, the current standard treatment for prophylaxis against stroke and systemic embolism in patients with atrial fibrillation, require regular monitoring and dose adjustment; an unmonitored, fixed-dose anticoagulant regimen would be preferable. The aim of this randomised, open-label non-inferiority trial was to compare the efficacy and safety of idraparinux with vitamin K antagonists. Methods: Patients with atrial fibrillation at risk for thromboembolism were randomly assigned to receive either subcutaneous idraparinux (2\ub75 mg weekly) or adjusted-dose vitamin K antagonists (target of an international normalised ratio of 2-3). Assessment of outcome was done blinded to treatment. The primary efficacy outcome was the cumulative incidence of all stroke and systemic embolism. The principal safety outcome was clinically relevant bleeding. Analyses were done by intention to treat; the non-inferiority hazard ratio was set at 1\ub75. This trial is registered with ClinicalTrials.gov, number NCT00070655. Findings: The trial was stopped after randomisation of 4576 patients (2283 to receive idraparinux, 2293 to receive vitamin K antagonists) and a mean follow-up period of 10\ub77 (SD 5\ub74) months because of excess clinically relevant bleeding with idraparinux (346 cases vs 226 cases; 19\ub77 vs 11\ub73 per 100 patient-years; p<0\ub70001). There were 21 instances of intracranial bleeding with idraparinux and nine with vitamin K antagonists (1\ub71 vs 0\ub74 per 100 patient-years; p=0\ub7014); elderly patients and those with renal impairment were at greater risk of such complications. There were 18 cases of thromboembolism with idraparinux and 27 cases with vitamin K antagonists (0\ub79 vs 1\ub73 per 100 patient-years; hazard ratio 0\ub771, 95% CI 0\ub739-1\ub730; p=0\ub7007), satisfying the non-inferiority criterion. There were 62 deaths with idraparinux and 61 with vitamin K anatagonists (3\ub72 vs 2\ub79 per 100 patient-years; p=0\ub749). Interpretation: In patients with atrial fibrillation at risk for thromboembolism, long-term treatment with idraparinux was no worse than vitamin K antagonists in terms of efficacy, but caused significantly more bleeding

Guinea pigs experimentally infected with vaccinia virus replicate and shed, but do not transmit the virus Cobaias infectadas experimentalmente com vírus vaccínia replicam e excretam, porém não transmitem o vírus

The origin of vaccinia viruses (VACV) associated with vesicular disease in cattle and humans in Southeast Brazil remains uncertain, yet the role of wild species in virus transmission has been suggested. This study investigated the susceptibility and transmission potential by guinea pigs (Cavia porcellus) - phylogenetically close to an abundant Brazilian rodent (Cavia aperea) - to two VACV strains (P1V and P2V) isolated from an outbreak of cutaneous disease in horses in Southern Brazil. Eight guinea pigs inoculated intranasally with P1V and P2V (10(6) TCID50.ml-1) did not develop clinical signs, but six animals shed virus in nasal secretions (day 1 to 9 post-inoculation - pi), developed viremia (between days 1 and 10 pi) and seroconverted to VACV. In spite of virus replication and shedding, the virus was not transmitted to sentinel animals by direct or indirect contact (aerosols) or through food and water contaminated with virus. These results demonstrate that, in spite of replicating and shedding the virus, guinea pigs do not transmit the virus upon experimental inoculation. This finding makes unlikely a possible participation of related species in VACV maintenance and transmission in nature.<br>A origem dos vírus vaccínia (VACV), envolvidos em surtos de doença vesicular em bovinos e humanos no Sudeste do Brasil, permanece desconhecida, e a participação de espécies silvestres na manutenção e transmissão do vírus tem sido sugerida. O objetivo deste trabalho foi investigar a susceptibilidade e o potencial de transmissão por cobaias (Cavia porcellus) - filogeneticamente relacionada a uma espécie de roedor, conhecido por preá (Cavia aperea), bastante abundante no país - a duas cepas de VACV (P1V e P2V) isoladas de um surto de doença cutânea em equinos no Rio Grande do Sul. Oito cobaias inoculadas pela via intranasal com uma mistura das amostras P1V e P2V (10(6) DICC50.ml-1) não apresentaram sinais clínicos, porém seis animais excretaram o vírus nas secreções nasais (1 a 9 dias pós-inoculação - pi), desenvolveram viremia (1 a 10 dias pi) e soroconverteram ao VACV. Apesar da replicação e excreção viral, o vírus não foi transmitido a sentinelas por contato direto, indireto (aerossóis) ou por água e alimentos contaminados com fezes deliberadamente contaminadas com o vírus. Esses resultados demonstram que, apesar de replicar e excretar o vírus, as cobaias não transmitem o VACV nas condições estudadas. Esses achados tornam pouco provável a participação de espécies relacionadas na manutenção e transmissão do VACV na natureza