Appropriate Anticoagulation Underutilized in Atrial fibrillation

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.

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Stopping Warfarin in Dementia Patients with Atrial Fib Associated With Increased Risk of Stroke and Death

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

Dr. Ariela Orkaby

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.

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Increase In Subdural Hematomas Associated With Increase Use of Antithrombotic Drugs


MedicalResearch.com Interview with:

David Gaist, MD, PhD</strong> Department of Neurology Odense University Hospital University of Southern Denmark Odense, Denmark

Dr. David Gaist

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.

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Which AFib Patients Should Resume Warfarin After Intracranial Hemorrhage?

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.

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Only High Risk Patients May Require Anticoagulation After Arthroscopic Knee Surgery

MedicalResearch.com Interview with:

Suzanne C. Cannegieter, M.D., Ph.D. Einthoven Laboratory  Leiden University Medical Center  The Netherlands

Dr. Suzanne Cannegieter,

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.

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Idarucizumab For Dabigatran Reversal: Updated Results Of The Re-verse Ad Study

MedicalResearch.com Interview with:

Dr. Charles Pollack MD Professor of Emergency Medicine Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia.

Dr. Charles Pollack

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.

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Laser-Assisted Technology Allows Easier Removal of IVC Filters

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

Dr. William T. Kuo

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.

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Use of Oral Anticoagulation at Time of PCI Surgery Linked To Increase in Adverse Events

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

Dr. Eric A. Secemsky

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.

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The GLORIA-AF Registry: Two Year Follow Up of Dabigatran for Non-Valvular A Fib Reported

MedicalResearch.com Interview with:

Menno Huisman, MD, PhD Associate professor Department of Medicine Leiden University Medical Center The Netherlands

Dr. Menno Huisman

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.

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Complex Stent Procedures May Require Longer Period of Antiplatelet Therapies

MedicalResearch.com Interview with:

Gennaro Giustino MD Resident Physician - Department of Medicine The Icahn School of Medicine at Mount Sinai

Dr. Gennaro Giustino

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.

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Many Atrial Fibrillation Patients At Risk of Stroke Receive Aspirin Instead of Appropriate Anticoagulation

MedicalResearch.com Interview with:

Jonathan Hsu, MD, MAS, FACC, FAHA, FHRS Assistant Professor Cardiac Electrophysiology, Division of Cardiology University of California, San Diego (UCSD)

Dr. Jonathan Hsu

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.

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Even on Anticoagulation Atrial Fibrillation Contributes to Dementia Risk

MedicalResearch.com Interview with:

T. Jared Bunch, MD Director of Heart Rhythm Research Medical Director for Heart Rhythm Services Intermountain Healthcare system

Dr. T. Jared Bunch

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.

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Idarucizumab– PRAXBIND Reverses Anticoagulant Effects of Dabigatran

MedicalResearch.com Interview with:

Dr. Charles Pollack MD MA Thomas Jefferson University Philadelphia, PA 19107

Dr. Charles Pollack

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.

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Physician Anticoagulant Strategies during PCI for Heart Attack Vary

MedicalResearch.com Interview with:

Eric Alexander Secemsky, M.D Research Fellow in Medicine Massachusetts General Hospital

Dr. Eric Secemsky

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.

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Does Metabolizer Status Matter in Acute Coronary Syndromes Treated With Prasugrel vs Clopidogrel?

MedicalResearch.com Interview with:

Professor Keith AA Fox Duke of Edinburgh Professor of Cardiology University of Edinburgh

Prof. Keith Fox

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).

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What Normalizes Bleeding Time Best After Coumadin Related Brain Bleed?

MedicalResearch.com Interview with:

Thorsten Steiner, MD, PhD Klinikum Frankfurt Hoechst and Heidelberg University Hospital Germany

Dr. Thorsten Steiner

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.
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Is the Evidence for the Anticoagulant Rivaroxaban Valid?

MedicalResearch.com Interview with:

Dr. Deborah Cohen

Dr. Deborah Cohen

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.

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History of Bleeding Helps Predict Risk of Bleeding from Anticoagulants

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

Prof. De Caterina

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.

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Study Finds Women Who Take Anticoagulants Can Use Hormonal Therapy

Ida Martinelli MD, PhD A Bianchi Bonomi Hemophilia and Thrombosis Center Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milan, Italy

Dr. Martinelli

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.

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For Medicare Patients, Dabigatran Offers Significant Cost Savings Over Warfarin

Geoffrey Barnes, MD, MSc Clinical Lecturer Cardiovascular Medicine and Vascular Medicine University of Michigan Health System

Dr. 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?

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.  Continue reading

Study Compares Anticoagulation Risk Scores in Atrial Fibrillation

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 CHADSand 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.

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Triple Anticoagulation Therapy Raises Bleeding Risk in Elderly Patients with AFib and Heart Attack

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.

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Oral Anticoagulation Medications Have Led To More Patients Treated For Atrial Fibrillation

Dr-Geoffrey-BarnesMedicalResearch.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.

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Duration of Anticoagulation After Primary Pulmonary Embolism Clarified

Professor Francis Couturaud, MD, PhD Department of Internal Medicine and Chest Diseases University Hospital Center of Brest Brest, FranceMedicalResearch.com Interview with:
Professor Francis Couturaud, MD, PhD
Department of Internal Medicine and Chest Diseases
University Hospital Center of Brest
Brest, France

Medical Research: What is the background for this study? What are the main findings?

Dr. Couturaud: Patients who have completed 3 to 6 months of anticoagulation for a first episode of pulmonary embolism that was not provoked by a major transient risk factor, such as surgery or prolonged immobilization, have a high risk of recurrent venous thromboembolism after stopping anticoagulation. In this high-risk population, extending anticoagulation beyond 3 to 6 months is associated with a major reduction in recurrences as long as the treatment is continued. However, whether this benefit is maintained thereafter remains uncertain, as in most previous studies, patients were not followed after treatment discontinuation. In addition, while extending anticoagulation is very effective in preventing recurrent venous thromboembolism, anticoagulation is also associated with an increased risk of bleeding. Therefore, in patients with a first episode of unprovoked pulmonary embolism, the optimal duration of anticoagulation remains uncertain.

In the PADIS-PE multicenter, double-blind, randomized trial that included 371 patients with a first episode of unprovoked pulmonary embolism initially treated during 6 months, we aimed to evaluate the benefit and risk of an additional 18 months of warfarin therapy versus placebo during the 18-month study treatment period and during an additional 2 years of follow-up after study treatment discontinuation.

The main findings are the followings: during the study treatment period, we found a 80% reduction in the relative risk of recurrent venous thromboembolism or major bleeding, mainly driven by the 90% risk reduction of recurrences; however, during the post-treatment follow-up period of two years, the benefit was lost, and the risks of recurrent venous thromboembolism and major bleeding were not different between the 2 groups. In addition, recurrent venous thromboembolism occurred as pulmonary embolism in 80% of cases (8% were fatal) and were unprovoked in 90% of cases.

Medical Research: What should clinicians and patients take away from your report?

Dr. Couturaud: Our study provides convincing result that extended but limited duration of anticoagulation does not improve the long-term prognosis of a first episode of unprovoked pulmonary.

The consequences for clinicians are the followings:

First, only two options of management should be discussed: either a conventional duration of 3 to 6 months or an indefinite duration of anticoagulation.

Second, more than ever, the individual risk factors of recurrent VTE if anticoagulation is stopped and risk factors of bleeding if anticoagulation is continued should be carefully identified and weighted in order to propose the most adequate long-term secondary prevention (long-term anticoagulation or specific prophylactic counseling in high-risk situations). This evaluation should also included patient’s preference.

Third, the benefit risk ratio of indefinite anticoagulation should be serially evaluated in these patients not only if indefinite anticoagulation is decided but also if anticoagulation is stopped as patient’s profile will change over the time (age, additional comorbidities, etc.) and in order to determine if anticoagulation should be stopped or started again.

For the patients, once the first episode of unprovoked pulmonary embolism, they should be informed about their high risk of recurrent venous thromboembolism if anticoagulation is stopped and their risk of bleeding if anticoagulation is continued. They also should be informed that recurrent venous thromboembolism occurs more often as pulmonary embolism; in this setting, patients should be informed about clinical symptoms of pulmonary embolism but also of deep vein thrombosis and the links between these two entities. This will help people to express their preferences.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Couturaud: : The first issue is to identify, among patients with unprovoked venous thromboembolism, those who have a lower risk of recurrence that may not justify indefinite anticoagulation. Several predictive scores, combining clinical variables such at gender, age, and tests such as D-dimer have been derived but prospective validation is not yet available.
The second issue is to explore long-term secondary thrombo-prophylaxis strategies with a lower risk of bleeding and a similar efficacy. This is currently the case with aspirin and low dose of Direct Oral Anticoagulants. However, additional studies are needed to determine if such strategies have a better benefit risk ratio than conventional anticoagulation.

Citation:

Professor Francis Couturaud, MD, PhD, & Department of Internal Medicine and Chest Diseases (2015). Duration of Anticoagulation After Primary Pulmonary Embolism Clarified 

RE-VERSE AD: Anticoagulant Effect of Dabigatran Reversed By New Drug

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.

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