Author Interviews, Clots - Coagulation, Stroke / 21.02.2016

MedicalResearch.com Interview with: Thorsten Steiner, MD, PhD Klinikum Frankfurt Hoechst and Heidelberg University Hospital Germany Medical Research: What is the background for this study? What are the main findings? Dr. Steiner: Background of the study is intracranial hemorrhage (ICH) related to vitamin-K antagonists. The mortality rate is about 60%. Main reason for the high mortality rate is hematoma expansion which occurs in about 50% during the acute phase right after the start of symptoms. We performed an investigator initiated randomized controlled trial (RCT) and found that a 4-factor prothrombin complex (PCC) is superior to fresh frozen plasma (FFP) in normalizing the international normalized ratio (INR) and prevents hematoma expansion. This let to more deaths within 48 hours in the FFP-group but had no clinical impact at 3 months - but our study was powered to detect INR normalization and not a clinical endpoint. (more…)
Author Interviews, BMJ, Clots - Coagulation, Heart Disease, Stroke / 06.02.2016

MedicalResearch.com Interview with: Dr. Deborah Cohen Associate Editor BMJ BMA House, Tavistock Square London Medical Research: What is the background for this study? What are the main findings? Dr. Cohen: Anyone familiar with warfarin understands the critical role of INR values in determining the proper dose for warfarin patients. The INR value in an individual patient is the most important piece of information a doctor considers when determining the warfarin dose. If the doctor gives too little warfarin then the patient may be at undue risk of stroke; if too much, the patient may be at undue risk of a major bleed. The BMJ investigation revealed that the INR device used to manage the ~7,000 warfarin patients in the ROCKET trial (which served as the basis for approval of the non-valvular atrial fibrillation indication) was defective. As such – doctors were relying upon a defective device in determining the dose of the warfarin patients – which has a direct influence on the stroke and bleeding risk in that patient. Since this was a comparative trial – any deficiency in the performance of the comparator arm (warfarin) would skew the results in favour of the study drug (rivaroxaban). Since INR directly influences strokes and bleeds – the primary efficacy and safety endpoints – it very much questions, if not undermines, the overall results of this trial. (more…)
Author Interviews, Clots - Coagulation, FDA, Heart Disease, JAMA, Johns Hopkins / 12.01.2016

MedicalResearch.com Interview with:
Victor Serebruany, MD, PhD
HeartDrug Research, Towson, Maryland
Department of Neurology Johns Hopkins University Baltimore, Maryland Medical Research: What is the background for this study? What are the main findings?

Dr. Serebruany: Missing data are common challenges to the validity of trial results, yet it is unclear how to characterize the extent of missing data.  We compared the published lost-to-follow-up rates to incomplete follow-up rates determined from subject records submitted to the FDA for major oral antithrombotic trials.  The 21 trials having both sets of rates included 270,089 patients followed for a median duration of 20 months.  The mean published lost-to-follow-up rates is 0.4% (median 0.3%, range 0.005% to 2%), consistently much lower than the FDA incomplete follow-up rates: mean 12% (median 13%, range 2% to 23%).  There is no correlation between the publication and FDA-calculated  rates (R 0.07, p = 0.76).   The FDA rates exceed greatly the endpoint rate differences: mean 1.3% (median 1,0%, range 0.2% to 3.0%). Medical Research: What should clinicians and patients take away from your report? Dr. Serebruany: That the FDA incomplete follow-up rates greatly exceed the endpoint rate differences raises questions of whether the endpoint differences may be due to differential follow-up rather than drug effect.  That they greatly exceed the measures routinely reported for trials, i.e., lost-to-follow-up rates, suggests that current trial reporting is inadequate.  Completeness of follow-up and other indicators of trial data quality should be considered when interpreting trial results. (more…)
Author Interviews, Blood Clots, Endocrinology, Hormone Therapy, Pharmacology / 07.01.2016

MedicalResearch.com Interview with: Ida Martinelli MD, PhD A Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Italy  Medical Research: What is the background for this study? What are the main findings? Dr. Martinelli: Hormonal therapies are associated with an increased risk of venous thromboembolism. Patients with acute deep-vein thrombosis or pulmonary embolism require anticoagulation, but women of childbearing potential require also an adequate contraception, as oral anticoagulants cross the placenta potentially leading to embryopathy or fetal bleeding. This study was aimed to evaluate the safety of hormonal therapies together with anticoagulant therapies in terms of recurrent venous thrombosis and uterine bleeding. We demonstrated for the first time that women who take oral anticoagulants can safely use hormonal therapies, as their risk of recurrent venous thromboembolism or uterine bleeding is not increased. (more…)
Author Interviews, Cancer Research, Clots - Coagulation, Sloan Kettering / 16.12.2015

MedicalResearch.com Interview with: Luke V. Selby, MD Research Fellow, Department of Surgery Vivian E. Strong, MD FACS Associate Attending Surgeon, Department of Surgery Memorial Sloan Kettering Cancer Center Medical Research: What is the background for this study? What are the main findings? Response: There was strong concern at our institution about the safety of providing pre-operative Venous Thromboembolism (VTE) chemoprophylaxis (in addition to our standard peri and post-operative prophylaxis) was unsafe.  To answer this question we administered a single dose of either low molecular weight heparin or unfractionated heparin to all eligible surgical patients at our institution over a six month period. When compared to identically selected patients operated on during the preceding 18 months, patients who received the pre-operative VTE chemoprophylaxis did not have higher rates of bleeding complications and had lower rates of DVT and pulmonary embolism (PE). (more…)
Author Interviews, Clots - Coagulation, Infections / 19.11.2015

MedicalResearch.com Interview with: Professor Adam Cunningham PhD Institute of Immunology and Immunotherapy MRC Centre for Immune Regulation University of Birmingham Medical Research: What is the background for this study? Dr. Cunningham: Our original question was “Why do people die from Salmonella infections that spread beyond the gut”. Some reasons are known but these do not account for all. In particular infants in sub-Saharan Africa seem particularly prone to Salmonella infections that in the West do no more than cause a self-limiting gastroenteritis. A puzzling feature of many of infections in such infants is that they do not have many bacteria in the blood, probably <10 / ml of blood, yet this low density is a strong predictor of death. Therefore, we thought that it may be the host response to the infection that complicates its control and contributes. (more…)
Author Interviews, Blood Clots, Orthopedics, PLoS / 16.11.2015

MedicalResearch.com Interview with: Banne Nemeth, MD and  Suzanne C. Cannegieter MD PhD Leiden University Medical Center The Einthoven Laboratory for Experimental Vascular Medicine Clinical Department of Epidemiology and Orthopedic Surgery Medical Research: What is the background for this study? What are the main findings? Dr. Nemeth: Clinicians cannot currently accurately predict who will develop venous thrombosis, but it would be very helpful to be able to identify individuals at high risk for venous thrombosis because the condition can be prevented by giving anticoagulants before a clot forms (thromboprophylaxis). The ability to predict venous thrombosis would be particularly useful in patients who have had a lower limb immobilized in a cast after, for example, breaking a bone. These patients have an increased risk of venous thrombosis compared to patients without cast immobilization. We developed and validated a prediction model to identify patients with plaster cast of the lower extremity who are at high risk to develop venous thrombosis. A clinical risk score named, L-TRIP(cast) score (Leiden Thrombosis Risk Prediction for patients with cast immobilization score), was developed containing 14 clinical risk factors such as age, sex, BMI, use of oral contraceptives and location of plaster cast. Patients that score 9 points or higher are classified as being at high risk for venous thrombosis. Clinicians may decide to prescribe thromboprophylaxis therapy for these patients. (more…)
Author Interviews, Clots - Coagulation, Heart Disease, Stroke, University of Michigan / 10.11.2015

MedicalResearch.com Interview with: Geoffrey Barnes, MD, MSc Clinical Lecturer Cardiovascular Medicine and Vascular Medicine University of Michigan Health System Medical Research: What is the background for this study? Dr. Barnes: Although warfarin has been the primary anticoagulant used for stroke prevention in atrial fibrillation for over 60 years, four new direct oral anticoagulants (DOACs) have been introduced into the market since 2010. Dabigatran, which directly inhibits thrombin, was found to have better prevention of ischemic stroke and a significant reduction in hemorrhagic stroke (bleeding strokes) for patients with atrial fibrillation at intermediate and high risk of stroke.  Prior cost-effectiveness studies have shown that dabigatran is cost-effective from both the societal and payer (usually Medicare) perspectives.  However, none of those studies looked at the patient’s out-of-pocket costs and the impact of prescription drug coverage Medical Research: What are the main findings? Dr. Barnes: We found that patients with prescription drug coverage (Medicare Part D) had significant cost savings when choosing dabigatran over warfarin.  This is primarily because of the reduction in both types of stroke as well not needing to have frequent blood draws, as are required by warfarin.  However, when patients do not have prescription drug coverage, the costs for dabigatran are quite high.  (more…)
Author Interviews, Clots - Coagulation, Heart Disease, JACC / 24.10.2015

H.A. (Hendrika) van den Ham PharmD Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University The Netherlands.MedicalResearch.com Interview with: H.A. (Hendrika) van den Ham PharmD Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences Utrecht University The Netherlands. Medical Research: What is the background for this study? What are the main findings? Dr. van den Ham: Atrial fibrillation (AF) is associated with a substantial risk of ischemic stroke and thromboembolism. The CHADS2 and the CHA2DS2-VASc risk scores are developed to guide the decision to prescribe anticoagulants. Recently a new clinically-based risk score, the ATRIA study risk score, was developed. We compared the predictive ability of the ATRIA risk score with the CHADS2 and CHA2DS2-VASc risk scores in a large, independent, community-based cohort of Atrial fibrillation patients in the United Kingdom. We found that the ATRIA score more accurately identified low risk patients that the CHA2DS2-VASc score assigned to higher risk categories.  Such reclassification of stroke risk could prevent overuse of anticoagulants in very low stroke risk patients with Atrial fibrillation. (more…)
Author Interviews, Clots - Coagulation / 19.10.2015

MedicalResearch.com Interview with: Karl Minges, MPH PhD Candidate Yale Graduate School of Arts & Sciences Yale School of Nursing Research Associate | Yale-New Haven Hospital Center for Outcomes Research & Evaluation (CORE) McDougal Graduate Career Fellow | Yale Office of Career Strategy   Medical Research: What is the background for this study? What are the main findings? Response: Pulmonary embolism, caused by a sudden blockage in the lung artery, is thought to be among the most treatable and preventable causes of death. This has been precipitated by several recent diagnostic and therapeutic advancements that have broadened the range of options for diagnosis, treatment, and management for pulmonary embolism in the past decade. In fact, the public health burden of pulmonary embolism is so great that the U.S. Surgeon General issued a Call to Action to prevent venous thromboembolism, comprising deep vein thrombosis and pulmonary embolism in 2008. Despite recent diagnostic and therapeutic advances in pulmonary embolism treatment and prevention, little is known regarding the national trends of pulmonary embolism among older adults – a population that is adversely at risk. In this study, we identified the recent trends in pulmonary embolism hospitalizations and outcomes, such as in-hospital, 30-day and 6-month mortality using a 100% sample of Medicare beneficiaries from 1999 to 2010. We examined instances where pulmonary embolism was the primary or most serious reason for which the patient was in the hospital. Trends by age, sex, and race cohorts were also examined. (more…)
Author Interviews, Brigham & Women's - Harvard, Clots - Coagulation, Heart Disease, JACC / 16.10.2015

Laura Mauri, MD, MSc Division of Cardiovascular Medicine, Department of Medicine Brigham and Women’s Hospital Boston, MA 02115MedicalResearch.com Interview with: Laura Mauri, MD, MSc Division of Cardiovascular Medicine, Department of Medicine Brigham and Women’s Hospital Boston, MA 02115  Medical Research: What is the background for this study? What are the main findings? Dr. Mauri: The Dual Antiplatelet Therapy (DAPT) Study, the largest randomized controlled trial to date comparing different durations of dual antiplatelet therapy (thienopyridine plus aspirin) after coronary stenting, found that patients who were free from major ischemic or bleeding events at 1 year after coronary stenting (either drug-eluting [DES] or bare metal [BMS]), and who were compliant with their antiplatelet therapy, experienced significant reductions in stent thrombosis and myocardial infarction (MI) but increases in moderate or severe bleeding when treated with 30 months of thienopyridine plus aspirin, as compared with 12 months. We analyzed these outcomes in a post hoc analysis of the subset of patients who received everolimus-eluting stents (EES) in the DAPT Study, because EES were the most frequently used stent in the study, and because data suggest that EES may have lower rates of stent thrombosis when compared with paclitaxel-eluting stents. We found that 30 months of dual antiplatelet therapy after coronary stenting (compared to 12 months) was associated with reduced rates of stent thrombosis and MI, no difference in a composite outcome of death, MI and stroke, and increased rates of moderate or severe bleeding. As found in the primary analysis of the DAPT Study, 30 months of dual antiplatelet therapy was associated with increased all-cause mortality, largely due to increased non-cardiovascular mortality. Bleeding-related deaths accounted for a minority of these deaths, where as cancer-related deaths in patients with pre-existing cancer diagnoses accounted for the majority of the mortality difference. (more…)
Author Interviews, Clots - Coagulation, CT Scanning, Emergency Care, Geriatrics / 24.09.2015

MedicalResearch.com Interview with: Dr Lim Beng Leong MBBS, MRCS (A&E), FAMS Jurong Health Services Emergency Department, Singapore  Medical Research: What is the background for this study? What are the main findings? Dr. Leong: It is common in the emergency department to see patients with warfarin who suffer a minor head injury (HI) with GCS >13. It is standard practice according to international guidelines to perform a plain CT scan of the head. What is contentious in the literature is the subsequent management of those patients with a normal initial CT scan. Practice is heterogeneous and includes a mandatory second CT scan at 24 hours mark or observation and repeat CT scan at the discretion of the attending doctor. We have found in our study that the "observe and repeat CT scan for symptomatic cases" approach only was safe as abnormal second CT scans were rare (1 in 295 cases). We traced the patients' course 2 weeks post discharge and none of the patients were re-admitted for reasons of delayed intra-cranial hemorrhage (ICH). However, the cohort of patients consist largely of geriatric patients with falls. More than 50% of these patients were hospitalized for more than 3 days; the longest of 2-3 weeks. They were likely to have various reasons that required longer hospitalizations apart from observation for delayed ICH, such as assessing for risk, etc. (more…)
Author Interviews, Clots - Coagulation, Heart Disease, JACC / 21.09.2015

MedicalResearch.com Interview with: Renato Valenti, MD David Antoniucci, MD Cardiology Department; Careggi Hospital Florence; Italy Medical Research: What is the background for this study? Response: Previous data have shown that high residual platelet reactivity in patients receiving clopidogrel is associated with high risk of ischemic events and cardiac death after PCI at short-  and long-term follow-up. Clopidogrel nonresponders patients of  the  REsponsiveness to CLOpidogrel and StEnt thrombosis (RECLOSE-2) ACS study received an increased dose of clopidogrel or switched to ticlopidine under light transmittance aggregometry (LTA) adenosine diphosphate  (ADP) test guidance. Despite some decrease of ADP test after treatment adjustment, there was no improvement on clinical outcome. Currently no evidence exists that the achievement of an optimal platelet aggregation inhibition in clopidogrel nonresponders  modifies  the risk profile of  these patients. The RECLOSE-3  study invesigated if a new antiplatet therapy with prasugrel in clopidogrel nonresponders can modify the risk profile of these patients and improve the outcome in term of cardiac mortality. From the RECLOSE-3 registry we identified  302 consecutive  patients who were clopidogrel nonresponders.  Nonresponders  switched to prasugrel therapy.  Due to the nonrandomized study design the clinical outcome of clopidogrel nonresponders switched to prasugrel (from RECLOSE-3 study) was compared with the historical cohort of clopidogrel nonresponders of the RECLOSE-2 ACS (248 patients)  study. The primary endpoint of the study was cardiac mortality. The 2-year cardiac mortality rate was  4.0% in the RECLOSE-3 group and 9.7% in the RECLOSE-2 group (p=0.007). The difference in 2-year cardiac mortality remained also considering exclusively patients  with ACS on admission: 3.2% and 9.7%, respectively, p=0.023.At the final model of multivariable analysis, prasugrel treatment was inversely related to the risk of  2-year cardiac death (HR 0.32; p=0.036)  after adjusting for ACS and other well known covariates related to the outcome. Medical Research: What are the main findings? Response: The main finding of the RECLOSE-3 study is that nonresponsiveness to clopidogrel may be a “modifiable risk factor” for cardiac death after PCI. Prasugrel treatment overcomes nonresponsiveness to clopidogrel and results in thrombotic risk similar to the one of clopidogrel responders. (more…)
AHA Journals, Author Interviews, Blood Clots, Brigham & Women's - Harvard, Medical Imaging / 17.09.2015

Peter Caravan, PhD Co-Director, Institute for Innovation in Imaging (I3) Martinos Center for Biomedical Imaging Massachusetts General Hospital Associate Professor of Radiology Harvard Medical SchoolMedicalResearch.com Interview with: Peter Caravan, PhD Co-Director, Institute for Innovation in Imaging (I3) Martinos Center for Biomedical Imaging Massachusetts General Hospital Associate Professor of Radiology Harvard Medical School Medical Research: What is the background for this study? What are the main findings? Dr. Caravan: The motivation for this work was to develop a technique that would allow the detection of thrombus (clot) anywhere in the body after injection of a molecular probe called 64Cu-FBP8.  Current techniques for thrombus detection are limited to specific vascular territories.  In instances where the location of the thrombus is unknown or if there is suspicion of multiple thrombi, then multiple imaging tests must be performed.  We sought to develop a test that could be used to find clots anywhere:  brain, thorax, abdomen, legs and in arteries, veins, or the cardiac chambers.  In addition to whole body thrombus detection, we sought a technique that could address some of the limitations with current thrombus imaging techniques.  For example computed tomography (CT), which is used to detect pulmonary emboli, requires a contrast agent that cannot be used in patients with poor kidney function.  Transesophageal echocardiography used to identify thrombus in the chambers of the heart requires that the patient be sedated. Our approach is to use a small peptide that recognizes the protein fibrin, which is a key component of blood clots.  We tagged the peptide with an isotope of copper, Cu-64, that allows the peptide to be detected by positron emission tomography (PET). 64Cu-FBP8 binds specifically to fibrin but not to other proteins in the blood and this means that the uptake in the clot is high while background signal is very low.  We combined PET imaging which finds the clot with CT imaging or magnetic resonance imaging (MRI).  By overlaying the PET image with the CT or MRI image, we could precisely localize the clot within the We were interested to see if the age of the clot impacted our ability to detect it.  We imaged animals with a total of 42 arterial or venous clots and then the images were analyzed by two reviewers who had no prior knowledge of the location of the clot.  Overall the accuracy was 98% for detection. Another key finding was that the uptake of 64Cu-FBP8 strongly correlated with the amount of fibrin in the clot and that younger, fresher clots had more fibrin than older clots.  This could be very useful in distinguishing newer clots which may be the source of cardiovascular events from older, clots that may pose less risk. We also showed using combined PET-MRI that we could detect multiple blood clots in the animal in a single whole body scan.  The procedure involves a single intravenous administration of 64Cu-FBP8 and clots in the deep veins of the legs or in the carotid arteries were readily detected. (more…)
Author Interviews, Heart Disease, JAMA, Thromboembolism / 01.09.2015

Line Melgaard MSc. Industrial Medicine, PhD student AALBORG Univerity Hospital Thrombosis Research Center Aalborg Aalborg Hospital Science and Innovation Center Aalborg DenmarkMedicalResearch.com Interview with: Line Melgaard MSc. Industrial Medicine, PhD student AALBORG Univerity Hospital Thrombosis Research Center Aalborg Aalborg Hospital Science and Innovation Center Aalborg Denmark Medical Research: What is the background for this study? What are the main findings? Response: In recent years, use of the CHA2DS2-VASc score in predicting ischemic stroke, thromboembolism, and death has extended beyond the original disease state (atrial fibrillation) for which it was proposed. In addition, it is recognized that the cluster of multiple stroke risk factors included within the CHA2DS2-VASc score increases the risk of ischemic stroke, thromboembolism, and death, whether or not atrial fibrillation is present. Thus, there is a need to study the extent to which concomitant atrial fibrillation modifies the pattern of the association between CHA2DS2-VASc score and the risk of ischemic stroke, thromboembolism, and death in patients with heart failure.
  • Our principal findings were that patients with heart failure had a high risk of ischemic stroke, thromboembolism, and death, whether or not atrial fibrillation was present.
  • Second, the CHA2DS2-VASc score was able to modestly predict these endpoints, and had a moderately high negative predictive value at 1-year follow-up.
  • Third, at high CHA2DS2-VASc scores (≥4), patients with heart failure without atrial fibrillation had high absolute risk of ischemic stroke, thromboembolism, and death, and the absolute risk increased in a comparable manner in patients with heart failure with and without atrial fibrillation, exhibiting a clear dose-response relationship. Indeed, the absolute risk of thromboembolic complications was higher among patients without atrial fibrillation compared to patients with concomitant atrial fibrillation at high CHA2DS2-VASc score (≥4).
(more…)
Author Interviews, Clots - Coagulation, Duke, Heart Disease, JACC / 09.08.2015

Connie N. Hess, MD, MHS Duke Clinical Research Institute Duke University Durham, North CarolinaMedicalResearch.com Interview with: Connie N. Hess, MD, MHS Duke Clinical Research Institute Duke University Durham, North Carolina Medical Research: What is the background for this study? What are the main findings? Dr. Hess: Guidelines recommend the use of anticoagulation for thromboembolic prophylaxis in atrial fibrillation and also recommend use of dual antiplatelet therapy to reduce cardiovascular events after myocardial infarction and percutaneous coronary intervention.  The use of triple therapy in patients with indications for DAPT and anticoagulation is challenging due to the increased bleeding risk associated with this regimen.  The optimal antithrombotic regimen in this population has not yet been defined. This study specifically focused on older patients, a population that is at greater risk for Atrial Fibrillation-related stroke and recurrent events after MI but also higher risk for bleeding. Despite a growing population of older patients with indications for triple therapy, these patients have been underrepresented in clinical trials and are therefore understudied. We found that relative to DAPT, patients on triple therapy had a similar risk of 2-year major adverse cardiac events but a significantly increased risk of bleeding requiring hospitalization, including greater risk of intracranial hemorrhage. (more…)
AHA Journals, Author Interviews, Clots - Coagulation, Outcomes & Safety, Surgical Research / 27.07.2015

Riyaz Bashir MD, FACC, RVTProfessor of Medicine Director, Vascular and Endovascular Medicine Department of Medicine Division of Cardiovascular Diseases Temple University Hospital Philadelphia, PA 19140MedicalResearch.com Interview with: Riyaz Bashir MD, FACC, RVT Professor of Medicine Director, Vascular and Endovascular Medicine Department of Medicine Division of Cardiovascular Diseases Temple University Hospital Philadelphia, PA 19140 Medical Research: What is the background for this study? Dr. Bashir: Catheter-based thrombus removal also known as Catheter Directed Thrombolysis (CDT) is a minimally invasive therapeutic intervention that has evolved over the past two decades to reduce the incidence of post thrombotic syndrome (PTS), a very frequent and disabling complication of proximal deep vein thrombosis (DVT). Catheter-based thrombus removal has been shown to reduce this lifestyle limiting complication of DVT and as a result we have observed a significant increase in the utilization rates of CDT across United States. Recent nationwide observational data suggests that higher adverse events such as intracranial hemorrhage rates and need for blood transfusions are seen with CDT use. Nonetheless specific reasons for these findings have not been explored prior to this study. Thread veins, also known as spider veins, are small veins which can appear on your face, thighs or calves and are an issue that many patients want help with. However, they are a cosmetic issue rather than a medical problem. People who suffer from the spider veins often feel that they affect their appearance and confidence and question why do we get thread veins? Medical Research: What are the main findings? Dr. Bashir: This study showed a significant inverse relationship between the institutional Catheter-based thrombus removal volumes and safety outcomes like death and intracranial hemorrhage. The institutions with higher volume of CDT cases annually (greater than or equal to 6 cases) were associated with lower in-hospital mortality rates and lower intracranial hemorrhage rates as compared to institutions, which performed less than 6 cases annually. This study also showed that at high volume institutions there was no difference in terms of death or intracranial bleeding rates between CDT plus anticoagulation versus anticoagulation alone. (more…)
Author Interviews, Clots - Coagulation, Heart Disease, JACC / 17.07.2015

Prof. Johan Bosmans Interventional cardiologist University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, BelgiumMedical Research Interview with: Prof. Johan Bosmans Interventional cardiologist University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium MedicalResearch: What is the background for this study? What are the main findings? Prof. Bosmans : Transcatheter aortic valve replacement (TAVR) has become standard of care for patients who cannot undergo surgery. With this, it is important to ensure that the risks associated with TAVR be fully understood, and if possible prevented. Even at this stage of the adoption of TAVR, large trials continue to provide information to the clinician about how to select the right patients to ensure the best possible outcomes. The ADVANCE Study is a prospective, multicenter study that evaluated the use of TAVR in 1015 patients at 44 experienced TAVR centers, which was designed to reflect routine clinical practice. We know that the risk of serious adverse events, such as stroke or transient ischemic attack (TIA), in post-TAVR patients can vary based on the timing before and after the procedure. A patient’s baseline demographics and medical history can affect their risk of procedure-related events as well as long-term outcomes. The manipulations required crossing the aortic valve and appropriately positioning any type of TAV has been thought to be related to procedural stroke events. Therefore, we performed a multivariable analysis looking for predictors of stroke – or stroke and TIA at 3 unique time periods (periprocedural, early and late) following TAVR. The most striking result from our analyses was that we were not able to identify any predictors of periprocedural (either during the procedure or on the day after) stroke, illustrating this very multifactorial etiology. We were able to show that being female, experiencing acute kidney injury or a major vascular complication positively predicted stroke during the early (2-30 days post procedure) time period. When we combined the outcome of stroke or TIA, we found that a history of prior atrial fibrillation (AF) was also a predictor. The only late predictor (day 31-730 post-procedure) of stroke was a history of coronary artery bypass grafting, which could reflect the patients’ risk of vascular disease. (more…)
Author Interviews, BMJ, Clots - Coagulation / 17.07.2015

MedicalResearch.com Interview with: Byung-Joo Park, MD, MPH, PhD Professor Department of Preventive Medicine Seoul National University College of Medicine Medical Research: What is the background for this study? What are the main findings? Response: Antidepressants and NSAIDs are each thought to increase the risk of abnormal bleeding.  However, previous studies found neither antidepressants nor NSAIDs alone to be associated with an increased risk of intracranial haemorrhage.  Our research found that combined use of NSADIs in antidepressant users showed the increased relative risk of intracranial haemorrhage risk within the initial 30-days of combined use. (more…)
Author Interviews, CHEST, Clots - Coagulation / 13.07.2015

MedicalResearch.com Interview with: David Jimenez PhD, FCCP Respiratory Department and Medicine Department Ramon y Cajal Hospital IRYCIS, and Alcala de Henares University Madrid Spain Medical Research: What is the background for this study? What are the main findings? Dr. Jimenez: Normotensive patients that have an estimated high-risk for pulmonary embolism (PE)-related complications (i.e., intermediate-risk PE) might benefit from surveillance in an intensive care setting or from the administration of specific advanced therapy. The Bova score was developed for identifying these patients. This study confirms the validity and reproducibility of the Bova score. (more…)
Author Interviews, Clots - Coagulation, JAMA, Surgical Research / 10.07.2015

Robert J. Lewandowski, MD FSIRAssociate Professor of Radiology Director of Interventional Oncology Department of Radiology Northwestern University Feinberg School of MedicineMedicalResearch.com Interview with: Robert J. Lewandowski, MD FSIR Associate Professor of Radiology Director of Interventional Oncology Department of Radiology Northwestern University Feinberg School of Medicine Medical Research: What is the background for this study? What are the main findings? Response: Retrievable inferior vena cava filters (rIVCF) were designed to provide temporary prevention from pulmonary embolism and then be removed when no longer needed. With permanent United States Food and Drug Administration (FDA) indication, these devices now account for the majority of IVC filters placed. Most rIVCFs placed are never removed because of poor clinical follow up, failed retrieval procedures, or patients not being offered the opportunity for filter removal secondary to prolonged dwell time; the latter has previously been correlated with retrieval failure. Retrievable IVCFs appear to be subject to greater device related complications (e.g., filter penetration of the IVC, filter migration, filter fracture) relative to permanent devices; furthermore, the rates of these complications appear to increase with filter dwell time. This prompted the FDA to issue a 2010 safety alert urging removal of rIVCFs once they are deemed no longer necessary. In the present study, we sought to determine whether rIVCF dwell time affects technical success of the retrieval procedure. Over a six-year period, 648 retrieval procedures were performed at our institution, with filter dwell times ranging from 0-108 months. We found that filter dwell time did not negatively impact IVC filter retrieval success nor did it increase our adverse events from the retrieval procedure. With advanced, adjunctive IVC filter retrieval techniques, rIVCFs can be safely and reliably removed despite long dwell times. (more…)
Author Interviews, Clots - Coagulation, NEJM / 23.06.2015

MedicalResearch.com Interview with: Dr. Charles Pollack Jr., MA, MD, FACEP Thomas Jefferson University Clinical Professor of Emergency Medicine Philadelphia, PA 19107 MedicalResearch: What is the background for this study? What are the main findings? Dr. Pollack: There are currently no approved specific reversal agents for non–vitamin K antagonist oral anticoagulants. Idarucizumab, an antibody fragment, was developed to specifically reverse the anticoagulant effects of the oral thrombin inhibitor, dabigatran. RE-VERSE AD is an ongoing, global Phase III patient study initiated in 2014 to investigate idarucizumab in emergency settings in patients taking dabigatran. We undertook this prospective cohort study to determine the safety of 5 g of intravenous idarucizumab and its capacity to reverse the anticoagulant effects of dabigatran in patients who either presented with serious bleeding (group A) or required an urgent invasive procedure (group B) which could not be delayed by eight hours. We intentionally designed the study with very broad inclusion criteria to reflect the types of patients who would require urgent anticoagulant reversal in real-world emergency settings. The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the determination at a central laboratory of the dilute thrombin time or ecarin clotting time. We also diligently collected clinical outcomes as secondary outcomes, being conscious that these may vary considerably due to the heterogeneity of the patients we included in the study. In our publication in the New England Journal of Medicine, we present the first results from the study, in an interim analysis of the data from the first 90 patients. The data showed that idarucizumab rapidly and completely reversed the anticoagulant effect of dabigatran in 88 to 98% of the patients who had had elevated clotting times at baseline. The reversal effect was evident within minutes. There were no safety concerns related to idarucizumab among the 90 patients involved in this study - including patients who were given idarucizumab on clinical grounds but were later found to have had normal results on clotting tests at baseline. This is consistent with the experience from the more than 200 volunteers who were administered idarucizumab in previous studies. (more…)
Author Interviews, Kaiser Permanente, Thromboembolism / 29.05.2015

MedicalResearch.com Interview with: Nathan Clark, PharmD Clinical pharmacy supervisor, anticoagulation and anemia management services and Thomas Delate, PhD Clinical research scientist Kaiser Permanente Colorado MedicalResearch: What is the background for this study? What are the main findings? Response: Patients with a history of blood clots are commonly prescribed warfarin, an anticoagulant, to decrease the body’s ability to form additional clots. Clinicians typically stop the use of warfarin in patients to reduce the risk of serious bleeding when invasive procedures, such as colonoscopy or orthopedic surgery are scheduled. However, when warfarin interruptions occur, patients are exposed to an increased risk of blood clots three to five days before and five or more days after invasive procedures. Bridge therapy with another, faster acting anticoagulant is often initiated in an attempt to reduce the patients’ risk for developing blood clots during that gap. Bridging has been a part of standard therapy for venous thromboembolism (VTE) patients undergoing invasive procedures for many years. But only limited data outlining the rates of bleeding and VTE recurrence were available to help clinicians analyze the risks and benefits of bridge therapy. We examined the electronic medical records of 1,178 patients with VTE who underwent 1,812 invasive diagnostic or surgical procedures between January 2006 and March 2012 that required the interruption of warfarin therapy. Study patients were categorized into three groups based on their annual risk of VTE recurrence without anticoagulant therapy. Within those groups, a total of 555 patients – 28.7 percent of low-risk, 33.6 percent of moderate-risk and 63.2 percent of high-risk patients – received bridging anticoagulant therapy. The 1,257 patients who did not receive bridge therapy interrupted their warfarin use and received no other anticoagulants during the perioperative period. The use of bridge therapy resulted in a 17-fold higher risk of bleeding without a significant difference in the rate of blood clot formation compared to patients who didn’t receive bridge therapy. In addition, there were no significant differences in the rates of blood clot occurrence or death between the bridged and non-bridged patient groups. (more…)
Author Interviews, BMJ, OBGYNE, Pharmacology, Thromboembolism / 27.05.2015

MedicalResearch.com Interview with: Yana Vinogradova, Research Fellow Division of Primary Care School of Medicine University of Nottingham Medical Research: What is the background for this study? What are the main findings? Response: Combined oral contraceptives are an effective method of birth control but do have measurable side effects.  One – common to all combined contraceptives and sometimes fatal – is an increased risk of venous thromboembolism (VTE).  A number of earlier studies investigated VTE risks for different types of hormonal contraceptives, but all were performed some years ago or had insufficient data to analyse newer preparations, while some included only healthy users and others did not adequately control for lifestyle and health issues.  The data used for this study were representative of the UK population and covered all currently prescribed drugs, with results adjusted for the widest possible range of available relevant factors. We found that the venous thromboembolism risks of combined oral contraceptives appear to fall into two distinct groups.  Newer drugs containing gestodene, desogestrel, drospirenone or cyproterone were associated with risks of VTE between 1.5 and 1.8 times higher than both the older compositions containing norethisterone or levonorgestrel and the relatively newer norgestimate.  While our findings are statistical associations between different compositions and venous thromboembolism risks, they do represent more comprehensive and reliable information for doctors making evidence-based prescribing decisions. (more…)
Author Interviews, Clots - Coagulation, JAMA, Radiology / 12.05.2015

MedicalResearch.com Interview with: Dott. Michelangelo Sartori U.O. di Angiologia e Malattie della Coagulazione Azienda Ospedaliera di Bologna Policlinico Sant'Orsola Malpighi Bologna Medical Research: What is the background for this study? What are the main findings? Response: The safety of withholding anticoagulation only on the basis of ultrasound imaging has not been evaluated in patients with suspected (Upper Extremity Deep Vein Thromobsis) UEDVT. The purpose of this management study was to evaluate the failure rate of ultrasound testing for UEDVT diagnosis in outpatients. Our data show that, similarly to the lower extremity, a negative complete ultrasound assessment of the upper extremity can safely exclude DVT. We found a 3-month VTE rate of 0.6% after a negative ultrasound and such figure is not different from the 3-month VTE incidence in management studies for lower limb DVT.  Thus anticoagulant therapy can be withheld for clinically suspected UEDVT after negative ultrasound examination without further testing in the ambulatory office setting. (more…)
AHA Journals, Author Interviews, Clots - Coagulation, Erasmus, Stroke / 17.10.2014

MedicalResearch.com: Interview Invitation S. Akoudad, MD Msc PhD candidate Dep. Epidemiology, Radiology, Neurology Erasmus MC, Rotterdam , the Netherlands Medical Research: What are the main findings of the study? Dr.  Vernooij: We found that compared to never users, coumarin users had a higher prevalence of deep or infratentorial microbleeds and probably also a higher incidence of any microbleeds. A higher maximum international normalized ratio (INR) was associated with deep or infratentorial microbleeds, and among coumarin users, a greater variability in INR was associated with a higher prevalence of microbleeds. (more…)
Author Interviews, Cancer Research, Lancet, Thromboembolism / 08.10.2014

MedicalResearch.com Interview with: Prof Martin H Prins MD Maastricht University Medical Centre, Maastricht, Netherlands Medical Research: What are the main findings of the study? Dr. Prins: Patients with active cancer, i.e. a cancer that was diagnosed or treated within 6 months before the episode, that was recurrent or metastatic, or that was diagnosed during treatment, who had a symptomatic episode of venous thromboembolism, were included in this pooled subgroup analysis of the Einstein DVT and PE studies. The incidence of recurrent venous thromboembolism was similar between groups. It occurred in 16 (5%) of 354 patients allocated to rivaroxaban and 20 (7%) of 301 patients allocated to enoxaparin and vitamin K antagonist (hazard ratio [HR] 0•67, 95% CI 0•35 to 1•30). Clinically relevant bleeding was also similar and occurred in 48 (14%) of 353 patients receiving rivaroxaban and in 49 (16%) of 298 patients receiving standard therapy (HR 0•80, 95% CI 0•54 to1•20). However, major bleeding was less frequent among rivaroxaban recipients and occurred in eight (2%) of 353 patients receiving rivaroxaban and in 15 (5%) of 298 patients receiving standard therapy (HR 0•42, 95% CI 0•18 to 0•99). Mortality was also similar. (more…)
Author Interviews, JAMA, Thromboembolism / 17.09.2014

Dr. Marc Carrier, MD MSc Scientist, Clinical Epidemiology, Ottawa Hospital Research Institute Physician, Hematology (Thrombosis), The Ottawa Hospital Associate Professor, Department of Medicine, Faculty of Medicine, and Research Chair in Venous Thromboembolism and Cancer (Tier 2) at the University of OttawaMedicalResearch.com Interview with: Dr. Marc Carrier, MD MSc Scientist, Clinical Epidemiology, Ottawa Hospital Research Institute Physician, Hematology, The Ottawa Hospital Associate Professor, Department of Medicine, Faculty of Medicine, and Research Chair in Venous Thromboembolism and Cancer (Tier 2) at the University of Ottawa MedicalResearch.com: What are the main findings of this study? Dr. Carrier: Venous thromboembolism (VTE), comprised of deep vein thrombosis and pulmonary embolism, is the third leading cause of cardiovascular death. There are many anticoagulant treatments available but there is little guidance about which treatment is most effective and safe. This systematic review and network meta-analysis evaluated eight different treatment options for acute Venous thromboembolism.  Forty-five trials were included in the analysis and there were no significant differences in clinical or safety outcomes associated with most treatment options when compared to the combination of LMWH-VKA.. (more…)