Heart Disease / 04.12.2014

MedicalResearch.com Interview with: Dr. Joanne van Ryn, PhD Department of CardioMetabolic Disease Research Boehringer Ingelheim GmbH & Co., Germany MedicalResearch: What is the background for this study? What are the main findings? Response: Idarucizumab is a humanized antibody fragment, or Fab, being investigated as a specific antidote to reverse the anticoagulant effect of dabigatran. Currently, there are no specific antidotes available for any of the newer oral anticoagulants, or NOACs, to complement the existing range of bleed management options during critical care situations. Idarucizumab is being developed to provide physicians with an additional therapeutic option they could consider should a patient require emergency intervention or if a patient experiences uncontrolled bleeding. Pre-clinical studies indicated idarucizumab binds specifically to and inhibits dabigatran. Phase I data with idarucizumab in healthy volunteers demonstrated the potential of idarucizumab to achieve immediate, complete and sustained reversal of dabigatran-induced anticoagulation. In that placebo-controlled study, idarucizumab did not cause any clinically relevant side effects. This phase I sub-study in 35 healthy volunteers showed that idarucizumab restores dabigatran-induced inhibition of fibrin formation at a small wound site. Fibrin, the main component of a blood clot, was assessed by measuring levels of fibrinopeptide A (FPA), a substance that is released when fibrin is formed. Fibrin formation was assessed after a small scratch, similar to a paper cut, was made. Measurements were conducted at baseline, after administration of dabigatran, and after subsequent administration of idarucizumab or placebo. The results showed that dabigatran almost completely inhibited the production of FPA at the wound site, and that idarucizumab restored FPA production:
  • At baseline, before the volunteers took dabigatran, the average level of FPA was 3981 ng/mL.
  • On day three, 2.5 hours after the volunteers took dabigatran, the average level of FPA was 208 ng/mL, an approximate 95 percent decrease compared to baseline.
  • On day four, 2.5 hours after the volunteers took dabigatran and 30 minutes after they were infused with 1 g, 2 g or 4 g of idarucizumab, FPA levels were 24 percent, 45 percent and 95 percent, respectively, of the average baseline level.
The restored fibrin production at the wound site after idarucizumab dosing with 2g or 4g also correlated with reversal of the dabigatran-anticoagulation activity in circulating blood. (more…)
Heart Disease / 04.12.2014

dr_John-Seeger MedicalResearch.com Interview with: Dr. John Seeger, PharmD, DrPH Department of Medicine, Brigham and Women’s Hospital Dr. Seeger: What is the background for this study? What are the main findings? Response: This study is part of an ongoing research program initiated in 2013 to assess prescribing patterns and real-world safety and effectiveness of oral anticoagulants, including dabigatran, for the reduction of stroke risk. The study program is expected to run through the end of 2016. Boehringer Ingelheim and Brigham and Women’s Hospital are aiming to gather data from more than 100,000 U.S. NVAF patients. Using a sequential matched cohort design, the safety and effectiveness of dabigatran compared to warfarin among patients with non-valvular atrial fibrillation (NVAF) receiving these medications in routine care settings can be assessed periodically. The interim findings at this stage come from 38,378 non-valvular atrial fibrillation patients in two health insurance databases, MarketScan (31,058 patients) and UnitedHealth (7,320 patients). The primary analysis follows patients from start of therapy until a switch or discontinuation of the anticoagulant, an outcome event, or disenrollment. The average follow-up was five months for patients in the dabigatran group and four months for those taking warfarin. The primary outcomes measured in the analysis are stroke and major hemorrhage. Interim findings from the combined databases showed a 25 percent reduction in the rate of major hemorrhage (hazard ratio [HR] 0.75, 95 percent confidence interval [CI] 0.65-0.87, 354 vs. 395 events) and a 23 percent reduction in strokes (HR 0.77, CI 0.54-1.09, 62 vs 69 events) for dabigatran compared to warfarin among these patients with NVAF. The database-specific results indicate a reduction in the rate of major hemorrhage with dabigatran (MarketScan: HR 0.78, CI 0.67- 0.91; UnitedHealth: HR 0.56, CI 0.36-0.86). In the larger MarketScan database, dabigatran reduced the stroke rate by 36 percent (HR 0.64, CI 0.44-0.95), while in the smaller UnitedHealth database, stroke rates were not different between the two anticoagulants, as there were only 26 strokes in total which led to wide confidence intervals (HR=1.62, CI 0.72-3.66). (more…)
Author Interviews, Clots - Coagulation, Genetic Research / 18.06.2014

MedicalResearch.com Interview with: David Ldr_david_l_brown . Brown, MD, FACC Professor of Medicine Cardiovascular Division Washington University School of Medicine St. Louis, MO 63110 MedicalResearch: What are the main findings of the study? Dr. Brown: This meta-analysis of randomized controlled trials showed that using a genotype-based warfarin dosing algorithm did not improve the process or outcomes of anticoagulation compared to using a clinical dosing algorithm. (more…)
Author Interviews, Clots - Coagulation, NEJM / 08.03.2013

 Author Interview: Sam Schulman M.D., FRCPC(C) Professor, Division of Hematology and Thromboembolism, Department of Medicine Associate Professor, Medicine, Karolinska Institute, Stockholm, Sweden Director, Clinical Thromboembolism Program Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario MedicalResearch.com Author Interview: Sam Schulman M.D., FRCPC(C) Professor, Division of Hematology and Thromboembolism, Department of Medicine Associate Professor, Medicine, Karolinska Institute, Stockholm, Sweden Director, Clinical Thromboembolism Program Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario MedicalResearch.com: What are the main findings of the study? Response: Similar effect of dabigatran as warfarin, 92% risk reduction compared to placebo. The risk of bleeding is reduced by almost 50% compared to warfarin but in comparison with placebo there is an increased risk of minor bleeding. No routine coagulation monitoring or dose adjustments are required, making the treatment convenient for patients and physicians. (more…)