Author Interviews, Heart Disease, JAMA, Stroke / 14.03.2017

MedicalResearch.com Interview with: Dr. Ying Xian MD PhD Department of Neurology, Duke Clinical Research Institute Duke University Medical Center Durham, North Carolina MedicalResearch.com: What is the background for this study? Response: Atrial fibrillation (AF) is the most common arrhythmia. AF increases the risk for stroke and accounts for 10% to 15% of all ischemic strokes. While the burden of AF-related stroke is high, AF is a potentially treatable risk factor. Numerous studies have demonstrated that vitamin K antagonists, such as warfarin, or non-vitamin K antagonist oral anticoagulants (NOACs), reduce the risk of ischemic stroke. Based on these data, current guidelines recommend adjusted-dose warfarin or NOACs over aspirin for stroke prevention in high-risk patients with Atrial fibrillation. (more…)
Alzheimer's - Dementia, Author Interviews, Brigham & Women's - Harvard, Geriatrics, Heart Disease, Stroke / 26.02.2017

MedicalResearch.com Interview with: Ariela Orkaby, MD, MPH Geriatrics & Preventive Cardiology Associate Epidemiologist Division of Aging, Brigham and Women's Hospital Instructor in Medicine, Harvard Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: Atrial Fibrillation is a common heart rhythm that affects 1 in 25 adults over age 60 and 1 in 10 adults over age 80. The feared consequence of atrial fibrillation is stroke, leading to the prescription of blood thinning medications (anticoagulants such as warfarin) to prevent strokes. However, there is an underutilization of these life-saving medications in older adults, and particularly in those who have dementia. In part, this is due to a lack of research and inclusion of older adults with dementia in prior studies. In this study, we used clinical Veterans Administration data, linked to Medicare, to follow 2,572 individuals over age 65 who had atrial fibrillation and until a diagnosis of dementia. The average age was 80 years, and 99% were male. We found that only 16% remained on warfarin. We used statistical methods to account for reasons why a patient would or would not be treated with warfarin and found that those who continued to take warfarin had a significantly lower risk of stroke (HR 0.74, 95% Confidence interval 0.54- 0.99, p=0.47) and death (HR 0.72, 95% CI 0.60-0.87, p<0.01) compared to those who did not continue to take warfarin, without an increased risk of bleeding. (more…)
Author Interviews, Heart Disease, JAMA / 25.02.2017

MedicalResearch.com Interview with: MedicalResearch.com: What is the background for this study? What are the main findings? Response: The incidence of subdural hematoma (SDH; a bleed located within the skull, but outside the brain) has been reported to be on the increase. Previous studies have shown an association between use of antithrombotic drugs and SDH. However, studies with updated estimates of this risk and with focus on current more complex and aggressive regimens of antithrombotic treatment are scarce. We therefore performed this study, where we identified 10,010 patients aged 20-89 years that were admitted with SDH in Denmark in 2000 through 2015. Preadmission use of antithrombotic drugs (low-dose aspirin, clopidogrel, vitamin K antagonist, e.g. warfarin, and direct oral anticoagulants) of these cases was compared to that of 400,380 individuals from the general population with no history of SDH (controls). We found that use of antithrombotic drugs was associated with an increased risk of subdural hematoma . The magnitude of this risk varied by type of antithrombotic, and was, e.g., low for use of low-dose aspirin, and highest for warfarin. Further, with a single exception (low-dose aspirin and dipyridamole), concurrent use of more than one antithrombotic drug was associated with higher risk of SDH, particularly if warfarin was taken along with an antiplatelet drug, e.g., low-dose aspirin or clopidogrel. Increasing use of antithrombotic drugs was observed in the study period. The incidence of subdural hematomas in the Danish population also increased markedly in the years 2000-2015, particularly among those aged 75+ years. Our study indicates that this increased incidence, can, at least partly, be explained by increased use of antithrombotic drugs. (more…)
Author Interviews, Heart Disease, JAMA, Stroke / 25.02.2017

MedicalResearch.com Interview with: Peter Brønnum Nielsen MD PhD Aalborg Thrombosis Research Unit Department of Clinical Medicine Faculty of Health Department of Cardiology, Atrial Fibrillation Study Group Aalborg University Hospital Aalborg, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients who sustain an intracranial hemorrhage (ICH) event are often excluded from randomized trials investigating stroke prevention in atrial fibrillation (AF) by use of oral anticoagulant treatment. (more…)
Author Interviews, NEJM, Orthopedics, Surgical Research, Thromboembolism / 06.12.2016

MedicalResearch.com Interview with: Suzanne C. Cannegieter, M.D., Ph.D. Einthoven Laboratory Leiden University Medical Center The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Patients who undergo arthroscopic knee surgery and patients who are treated with casting of the lower leg are at increased risk for venous thromboembolism (VTE). It is uncertain whether thromboprophylaxis is effective in these situations to prevent VTE. For both indications, several trials have been performed to evaluate the effectiveness of anticoagulant prophylaxis. However, an overall risk–benefit balance could not be established because of methodologic shortcomings; hence, there has been reluctance to establish international guidelines regarding the use of anticoagulant therapy for either of these indications. (more…)
Author Interviews, Pharmacology / 02.12.2016

MedicalResearch.com Interview with: Dr. Charles Pollack MD Professor of Emergency Medicine Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia. MedicalResearch.com: What is the background for this study? What are the main findings? Response: RE-VERSE AD™ is a multinational, open-label cohort Phase III trial studying the safety and efficacy of idarucizumab (PRAXBIND) to reverse the anticoagulant effects of dabigatran (PRADAXA) in patients with life-threatening or uncontrolled bleeding, or those who require emergency procedures. It is the largest patient study investigating a reversal agent for a novel oral anticoagulant (NOAC) in real world emergency settings. At the American Heart Association’s Scientific Sessions 2016, we presented updated results from 494 patients participating in the ongoing study, showing that administration of 5g of idarucizumab immediately reversed the anticoagulant effect of dabigatran. (more…)
Author Interviews, CHEST, Clots - Coagulation, Surgical Research / 02.11.2016

MedicalResearch.com Interview with: William T. Kuo, MD, FSIR, FCCP, FSVM Director, Stanford IVC Filter Clinic Director, IR Fellowship Program Founding Director, IR-DR Residency Program Associate Professor, Interventional Radiology Stanford University Medical Center Stanford, CA MedicalResearch.com: What is the background for this study? What are the main findings? Response: In the USA, over 250,000 IVC filters are now implanted each year, and rising filter use has led to an increase in filter-related morbidity and recognition of the potential complications from indwelling IVC filters. Consequently, the FDA has issued two safety communications alerting all physicians caring for patients with IVC filters to consider removing the filter as soon as protection from pulmonary embolism is no longer needed: http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm221676.htm http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm396377.htm?so urce=govdelivery&utm_medium=email&utm_source=govdelivery Despite heightened awareness, up to 40-60% of IVC filters cannot be easily removed using standard methods alone, after the filter becomes firmly embedded. Additionally, many patients have undergone prior placement of a permanent-type filter not even designed for retrieval, leaving them with few options for safe device removal. Although all of these patients can develop filter-related morbidity especially after chronic implantation, there is currently no routine option for removing embedded IVC filters refractory to standard retrieval methods. Our 5-year first-in-human study of a novel procedure—laser-assisted filter removal— demonstrates the safety and efficacy of this technique to treat such patients. In a cohort refractory to standard retrieval methods and high force, endovascular laser-assisted retrieval was overall safe and successful in removing a variety of filter types including permanent filters, regardless of dwell time and without the need for open surgery. (more…)
AHA Journals, Author Interviews, Beth Israel Deaconess, Brigham & Women's - Harvard, Clots - Coagulation, Heart Disease / 18.10.2016

MedicalResearch.com Interview with: Eric A. Secemsky, MD MSc Interventional Cardiology Fellow Massachusetts General Hospital Harvard Medical School Fellow, Smith Center for Outcomes Research in Cardiology Beth Israel Deaconess Medical Center MedicalResearch.com: What is the background for this study? Response: Use of oral anticoagulant (OAC) therapy prior to coronary stenting is a significant predictor of post-procedural bleeding events. Previous studies have estimated that the frequency of chronic OAC use among patients undergoing percutaneous coronary intervention (PCI) is between 3% to 7%. Yet many of these analyses examined select patient populations, such as those admitted with acute myocardial infarction or atrial fibrillation, and preceded the market approval of non-vitamin K antagonist oral anticoagulants (NOACs). As such, the contemporary prevalence of OAC use among all-comers undergoing PCI, as well as associated risks of adverse events, are currently unknown. Therefore, we used PCI data from a large, integrated healthcare system to determine current use of oral anticoagulant use among all-comers undergoing coronary stenting and the related short- and long-term risks of therapy. (more…)
Author Interviews, Clots - Coagulation, Heart Disease, Stroke / 13.09.2016

MedicalResearch.com Interview with: Menno Huisman, MD, PhD Associate professor Department of Medicine Leiden University Medical Center The Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: GLORIA™-AF is one of the largest ongoing global registry programs examining the use of oral antithrombotic agents in real-world clinical practice. The program is designed to characterize the population of newly diagnosed patients with non-valvular atrial fibrillation (NVAF) at risk for stroke, and to study patterns, predictors and outcomes of different regimens for stroke prevention. At the ESC Congress 2016, we presented the first Phase II results of GLORIA-AF from approximately 3,000 NVAF patients, which showed that treatment with PRADAXA was associated with low incidences of stroke, major bleeding and life threatening bleeding. Less than 1% of PRADAXA-treated patients experienced a stroke over two years (0.63%). Major bleeding occurred in 1.12% of PRADAXA-treated patients and 0.54% experienced a life-threatening bleed. (more…)
Author Interviews, Clots - Coagulation, Heart Disease, JACC, Surgical Research / 30.08.2016

MedicalResearch.com Interview with: Gennaro Giustino MD Resident Physician - Department of Medicine The Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Response: A period of dual antiplatelet therapy (DAPT) is required after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). The pathophysiological rationale for DAPT after DES-PCI is predicated on the need to prevent stent-related thrombotic complications while vascular healing and platform endothelialization are ongoing, a process that seems to last between 1 and 6 months with new-generation DES. Whether to extend DAPT after this mandatory period in order to provide a broader atherothrombotic risk protection (for stent-related and non-stent-related atherothrombotic events) is currently a matter of debate. Current guidelines recommend at least 6 months of DAPT after PCI in patients with stable coronary artery disease (CAD) and at least 12 months of DAPT in patients presenting with acute coronary syndrome (ACS). While, several risk scores have been developed to guide clinical decision making for DAPT intensity and duration (namely the DAPT score and the PARIS risk scores) little attention has been payed so far to PCI complexity and the extent of CAD to guide duration of DAPT. In fact irrespective of clinical presentation, patients undergoing more complex PCI procedure (likely due to greater coronary atherosclerotic burden) may remain at greater risk for ischemic events and therefore may benefit of prolonged, or more intense, DAPT. (more…)
Author Interviews, Heart Disease, JACC, UCSD / 22.06.2016

MedicalResearch.com Interview with: Jonathan Hsu, MD, MAS, FACC, FAHA, FHRS Assistant Professor Cardiac Electrophysiology, Division of Cardiology University of California, San Diego (UCSD) MedicalResearch.com: What is the background for this study? Response: Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide and imparts significant stroke risk. In patients with AF determined to be at intermediate to high risk for thromboembolism, anticoagulation with warfarin (a vitamin K antagonist) or the newer non-vitamin K antagonist oral anticoagulants clearly reduces morbidity and mortality compared to aspirin. We sought to evaluate practice patterns of cardiovascular specialists in the United states to determine how often AF patients at risk for stroke are prescribed aspirin over oral anticoagulation, and predictors of this practice. (more…)
Alzheimer's - Dementia, Author Interviews, Heart Disease / 06.05.2016

MedicalResearch.com Interview with: T. Jared Bunch, MD Director of Heart Rhythm Research Medical Director for Heart Rhythm Services Intermountain Healthcare System MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Bunch: Approximately 6 years ago we found that patients with atrial fibrillation experienced higher rates of all forms of dementia, including Alzheimers disease. At the time we started to ask the questions of why this association existed. We know that atrial fibrillation patients experience higher rates of stroke. These patients are placed on blood thinners, most commonly warfarin, to lower risk of stroke which at the same time expose that patient to a higher risk of intracranial bleeding. One possibility to explain the association was that perhaps dementia in the manifestation of many small clots or bleeds in the brain that in total lead to cognitive decline. If this is the case, then the efficacy and use of anticoagulation is very important in atrial fibrillation patients. We conducted additional studies that showed this to be the case. In patients with no history of dementia, managed long-term with warfarin anticoagulation, those that had levels that were frequently too higher or too low that resulted in poor times in therapeutic range, experienced significantly higher rates of dementia. The risk was highest in younger atrial fibrillation patients that were less than 80 years of age. We then found that in atrial fibrillation patients that were frequently over anticoagulated and also use an antiplatelet agent, aspirin or plavix, the dementia rates nearly doubled. At this point we raised the question if atrial fibrillation increased the risk beyond anticoagulation, or does anticoagulation efficacy drive most of the risk. This question formed the background of the current study. (more…)
Author Interviews, Heart Disease / 15.04.2016

MedicalResearch.com Interview with: Dr. Charles Pollack MD MA Thomas Jefferson University Philadelphia, PA 19107 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Pollack:: We are continuing research on PRAXBIND in the ongoing global phase III patient study, RE-VERSE AD™. RE-VERSE AD includes two groups of dabigatran patients: those who had serious bleeding or those who required an urgent procedure. At ACC, we presented results from an updated interim analysis from 123 patients enrolled in RE-VERSE AD™, which showed a single 5g of PRAXBIND immediately reversed the anticoagulant effect of dabigatran in all patients evaluated. (more…)
Author Interviews, Heart Disease / 26.03.2016

MedicalResearch.com Interview with: Eric Alexander Secemsky, MD, MSc Fellow in Cardiovascular Medicine Massachusetts General Hospital Harvard Medical School Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center MedicalResearch.com: What is the background for this study? Dr. Secemsky: Strategies to reduce bleeding, such as the selective use of procedural anticoagulants, have become an integral component of current percutaneous coronary intervention (PCI) practice to decrease adverse outcomes. For instance, previous randomized clinical trials had demonstrated that use of bivalirudin, a direct thrombin inhibitor, reduces major bleeding events following PCI among patients presenting with acute myocardial infarction (AMI) compared with unfractionated heparin (UFH). These findings resulted in a major increase in bivalirudin use during PCI. However, more recent trials have contradicted these results and created uncertainty as to the relative safety and effectiveness of bivalirudin therapy. In addition, current United States guidelines do not endorse a primary antithrombotic strategy during PCI, leaving the choice of procedural anticoagulant to the discretion of the physician operator. As such, we wanted to determine how bivalirudin was currently being used among United States PCI operators and how usage may have changed in light of these trial findings. (more…)
Author Interviews, Clots - Coagulation, Genetic Research, Heart Disease, JACC / 23.02.2016

MedicalResearch.com Interview with: Professor Keith AA Fox Duke of Edinburgh Professor of Cardiology University of Edinburgh Medical Research: What is the background for this study? Prof. Fox: From previous reports, certain alleles of CYP2C19 are associated with reduced enzymatic function and reduced conversion of clopidogrel to the active metabolite. Patients carrying these reduced function alleles (reduced metabolizers) exhibit higher platelet reactivity when treated with clopidogrel, compared with patients without reduced-function alleles (extensive metabolizers). However, the relationship of CYP2C19 genotype and outcomes in medically managed patients with acute coronary syndromes (ACS) is not known. Medical Research: What are the main findings? Prof. Fox: There was no association between CYP2C19 metabolizer status (EM vs. RM) and the primary composite endpoint of cardiovascular death, myocardial infarction (MI), or stroke (hazard ratio [HR]: 0.86). EM and RM patients had similar rates of the primary endpoint whether treated with prasugrel (HR: 0.82) or clopidogrel (HR: 0.91; p for interaction non significant). (more…)
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, Heart Disease / 20.01.2016

More on Anticoagulants on MedicalResearch.com MedicalResearch.com Interview with: Prof. Raffaele De Caterina M.D., Ph.D University Cardiology Division G. d'Annunzio University Medical Research: What is the background for this study? What are the main findings? Dr. De Caterina: There is uncertainty on how to predict bleeding upon treatment with anticoagulants, because bleeding risk scores and thromboembolic risk score fare very similarly in predicting bleeding, making the net clinical benefit difficult to assess in the single patient. Here we find that a history of bleeding – even minor bleeding – has an important prognostic value on the risk of future bleeding – virtually all sorts of future bleeding, with the notable exception of intracranial hemorrhage. Some novel oral anticoagulants (NOACs), such as apixaban, studied here, reduce the risk of major bleeding, and appear to benefit independent of the bleeding history. (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, 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, Duke, Heart Disease, JACC / 09.08.2015

Connie N. Hess, MD, MHS Duke Clinical Research Institute Duke University Durham, North Carolina MedicalResearch.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…)
Author Interviews / 22.07.2015

Dr-Geoffrey-Barnes 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? What are the main findings? Dr. Barnes: While warfarin has been the primary oral anticoagulant used for over 60 years, a new class of anticoagulants known as ‘direct oral anticoagulants’ (including dabigatran, rivaroxaban and apixaban) have been introduced within the last 5 years. These newer medications were developed to be easier for patients and physicians to use. While early data suggested quick adoption of these medications, there had not been a nation-wide assessment of their use and how specific diseases influenced the use of specific oral anticoagulants. Using a national sample of office visits, we generated national estimates of oral anticoagulant use for patients between 2009 and 2014. The primary finding is that total number of office visits where an anticoagulant was used increased from 2.05 million to 2.83 million between 2009 and 2014, largely driven by a rapid increase in the use of the direct oral anticoagulant medications. Specifically among patient visits for atrial fibrillation, the total number of visits where an oral anticoagulant was used increased from 52% to 67%. This is important because there has long been concern about “under treatment” of atrial fibrillation and the risk of stroke for patients who do not receive anticoagulation. This study suggests that the direct oral anticoagulants may be helping to protect more patients with atrial fibrillation from strokes. (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, Heart Disease, Kidney Disease / 28.02.2015

Dr. Simonetta Genovesi MD Department of Health Science University of Milano-Bicocca, Monza Italy Nephrology Unit San Gerardo Hospital, Monza, Italy MedicalResearch.com Interview with: Dr. Simonetta Genovesi MD Department of Health Science University of Milano-Bicocca, Monza Italy Nephrology Unit San Gerardo Hospital, Monza, Italy MedicalResearch: What is the background for this study? Dr. Genovesi: The prevalence of atrial fibrillation (AF) in patients with end-stage renal disease (ESRD) on hemodialysis (HD) is high. The presence of atrial fibrillation increases the risk of thrombo-embolic stroke in the general population. The treatment of choice for reducing thrombo-embolic risk in AF patients is oral anticoagulant therapy (OAT) with warfarin. However, the use of warfarin in HD patients is controversial because of the high risk of bleeding and the fact that it is not demonstrated a clear protection against the risk of stroke in this population. The purpose of the study was to prospectively evaluate the effect of OAT on the risk of mortality, stroke and bleeding in HD population. MedicalResearch: What are the main findings? Dr. Genovesi: In our hemodialysis population oral anticoagulant therapy does not increase the risk of total mortality, while antiplatelet agents are associated with an increased risk of death of about 70%. The continuous use of warfarin tends to be associated with improved survival as compared with individuals who discontinued the medication during the follow-up, but the incidence of thrombo-embolic events is not different in OAT subjects as compared with those who do not take it. Moreover, bleeding events are more frequent in patients taking warfarin, although the maintenance over time of an INR in the therapeutic range wards against the risk of bleeding. (more…)
Author Interviews, Heart Disease, JAMA, Karolinski Institute / 18.02.2015

Karolina Szummer, MD, PhD Section of Cardiology, Department of Medicine Karolinska Institutet Karolinska University Hospital Stockholm, Sweden MedicalResearch.com Interview with: Karolina Szummer, MD, PhD Section of Cardiology, Department of Medicine Karolinska Institutet Karolinska University Hospital Stockholm, Sweden Please note: This work is comparing the anticoagulant fondaparinux with low-molecular-weight heparin (not heparin). Medical Research: What is the background for this study? What are the main findings? Dr. Szummer: Since the publication of the OASIS-5 trial in 2006, many hospitals chose to change their medical practice and start using fondaparinux instead of low-molecular-weight heparin in the treatment of myocardial infarctions. In this study from the nation-wide near-complete myocardial infarction registry we were able to follow how the use of fondaparinux instead of low-molecular-weight heparin translated in clinical life was associated to a reduction in bleeding events and death. It is a very satisfying study, that confirms that the randomized clinical trial results are transferred with improvements in outcome to the treated patients. (more…)
Author Interviews, Heart Disease / 16.12.2014

Winnie Nelson PharmD, MS, MBA Director, Health Economics & Outcomes Research Janssen Pharmaceuticals MedicalResearch.com Interview with: Winnie Nelson PharmD, MS, MBA Director, Health Economics & Outcomes Research Janssen Pharmaceuticals Medical Research: What is the background for this study? What are the main findings? Dr. Nelson: Although warfarin has long served as the standard of care for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), research has shown nearly one-third of international normalized ratio (INR) levels among stabilized patients on warfarin are out-of-range. Data recently published in the International Journal of Clinical Pharmacy underscores the potential complications of out-of-range INRs, with the aim of informing patient care. The analysis of a U.S. Veterans Health Administration dataset showed out-of-range INRs were associated with a significantly increased risk of adverse clinical outcomes, including stroke and major bleeding. Of particular interest, the study also showed the magnitude of risk of thromboembolic events – such as ischemic stroke – was several folds higher in sub-therapeutic INR levels (i.e., INR <2) than risk of bleeding events when INR measures were >3. In another words, the research found more risks to patients when INRs were too low than when INRs were too high. (more…)
Author Interviews, Heart Disease, Kidney Disease / 11.12.2014

Anders Nissen Bonde MBs Department of Cardiology Copenhagen University Hospital Gentofte, Gentofte, Denmark MedicalResearch.com Interview with: Anders Nissen Bonde MBs Department of Cardiology Copenhagen University Hospital Gentofte, Gentofte, Denmark Medical Research: What is the background for this study? What are the main findings? Response: Patients with severe chronic kidney disease have been excluded from randomized trials of antithrombotic therapy in atrial fibrillation.They represent a very fragile group as they are both at increased risk of stroke/thromboembolism and major bleedings, and previous observational studies have had conflicting conclusions regarding the safety and benefits of the treatment. A previous study from our department reported both increased risk of bleeding and reduced risk of stroke with warfarin. We wanted to assess the net clinical benefit of aspirin and warfarin in these patients, balancing stroke and major bleeding associated with the treatment. (more…)