Dual Antiplatelet Therapy Found Beneficial Over Aspirin Alone Following CABG Surgery

MedicalResearch.com Interview with:

Nayan Agarwal MD Intervention Cardiology Fellow, University of Florida, Gainesville, FL

Dr. Agarwal

Nayan Agarwal MD
Intervention Cardiology Fellow
University of Florida,
Gainesville, FL

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Optimal antiplatelet strategy post CABG remains controversial with guidelines still evolving. Though aspirin monotherapy is the therapy of choice, but some studies have suggested a benefit of dual antiplatelet (DAPT). Question also remains if choice of antiplatelet therapy strategy is influenced by clinical presentation (acute coronary syndrome [ACS] versus non ACS) or CABG technique ( off pump versus on pump).

The current meta-analysis of 8 randomized control trials and 9 observational studies with a total of 11,135 patients demonstrated that at a mean follow up of 23 months, major adverse cardiac events (MACE) (10.3% versus 12.1%, RR 0.84, confidence interval (CI) 0.71-0.99); all-cause mortality (5.7% versus 7.0%, RR 0.67, CI 0.48-0.94) and graft occlusion (11.3% versus 14.2%, RR- 0.79, CI- 0.63- 0.98) were less with DAPT compared with aspirin monotherapy. There was no difference in myocardial infarction, stroke, or major bleeding between the 2 groups. Subgroup analysis demonstrated that benefit of DAPT was independent of clinical presentation (ACS versus non ACS) or CABG technique (off pump versus on pump).

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Anticoagulant Warfarin May Lower Cancer Risk

MedicalResearch.com Interview with:
Gry Haaland, MD

James Lorens PhD, Professor
The Department of Biomedicine
University of Bergen

 MedicalResearch.com: What is the background for this study?

Response: Antitumor activity of the common blood thinner warfarin has been reported in several experimental cancer model systems. We therefore considered whether warfarin is cancer protective.

Using the comprehensive national health registries in Norway, we examined cancer incidence among a large number of people taking warfarin (92,942) and compared to those not taking warfarin (more than 1.1 million).

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Chewing Loading-Dose of Ticagrelor Enhanced Platelet Inhibition in Heart Attack Patients

MedicalResearch.com Interview with:

Elad Asher, M.D, M.H.A Interventional Cardiologist, Director Intensive Cardiac Care Unit Deputy Director Heart Institute Assuta Ashdod Medical Cent

Dr. Asher

Elad Asher, M.D, M.H.A
Interventional Cardiologist,
Director Intensive Cardiac Care Unit
Deputy Director Heart Institute
Assuta Ashdod Medical Center

MedicalResearch.com: What is the background for this study?

Response: Dual antiplatelet therapy represents the standard care for treating ST elevation myocardial infarction (STEMI) patients. Given the higher risk of peri-procedural thrombotic events in patients undergoing primary percutaneous coronary intervention (PPCI), there is a need to achieve inhibition of platelet aggregation (IPA) more promptly. Although chewing ticagrelor has been shown to be more efficient for IPA in stable coronary disease and in patients with acute coronary syndrome (ACS)/non-ST elevation myocardial infarction (NSETMI), there are no studies that have specifically assessed the efficacy and safety of chewing ticagrelor in STEMI patients. Therefore, the aim of our study was to investigate whether chewing ticagrelor (180mg) loading dose is associated with more favorable platelet inhibitory effects compared with the conventional way of swallowing whole tablets loading dose in STEMI patients undergoing PPCI.

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Dementia Incidence Lower For Atrial Fibrillation Patients Treated With Anticoagulation

MedicalResearch.com Interview with:

Dr. Leif Friberg MD, PhD Associate professor in cardiology Karolinska Institute Friberg Resarch Stockholm, Sweden 

Dr. Leif Friberg

Dr. Leif Friberg MD, PhD
Associate professor in cardiology
Karolinska Institute
Friberg Resarch
Stockholm, Sweden 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: I have been doing research on atrial fibrillation and stroke risk for many years and knew that the very common heart arrhythmia is associated with a 40% increased risk of dementia. Considering that that 12-15% of 75 years olds have this arrhythmia, and even more at higher ages, the problem is significant to say the least.

The mechanism behind stroke in atrial fibrillation is that blood clots are formed in the heart. When these are dislodged they travel with the blood stream and may get stuck in the narrow vessels of the brain where they stop blood flow causing brain infarction or stroke. Oral anticoagulant drugs like warfarin or the newer so called NOAC (new oral anticoagulant) drugs are highly efficient in preventing formation of these large blood clots and offer at least 70% risk reduction. Now, blood clots come in different sizes. There are also microscopic clots that do not cause symptoms of stroke but all the same eat away at the brain at a slow but steady pace. Imaging studies shows this after only a few months or even weeks of atrial fibrillation. Our hypothesis was therefore: If anticoagulants are so effective in protecting against large clots, will they not help against the small ones too?

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Genetic Testing Reduces Risk Of Side Effects From Anticoagulation After Surgery

MedicalResearch.com Interview with:

Anne R. Bass, MD Associate Professor of Clinical Medicine Weill Cornell Medical College Rheumatology Fellowship Program Director Hospital for Special Surgery New York, NY 10021

Dr. Bass

Anne R. Bass, MD
Associate Professor of Clinical Medicine
Weill Cornell Medical College
Rheumatology Fellowship Program Director
Hospital for Special Surgery
New York, NY 10021

MedicalResearch.com: What is the background for this study?

Response: Blood thinners are used after orthopedic surgery to prevent blood clots from forming in the legs and traveling to the lungs. They are also used in patients with certain heart diseases to prevent strokes. Blood thinners, like warfarin, are effective but can be associated with serious bleeding complications, especially if the wrong dose is given. Genetic testing can help doctors predict the right warfarin dose to use in an individual patient.

In this trial, ≈1600 elderly patients undergoing hip or knee replacement were randomly assigned to receive warfarin dosing based on genetics plus clinical factors (like height, weight and gender), or based on clinical factors alone. The specific genes tested wereVKORC1, CYP2C9, and CYP4F2 which influence warfarin metabolism and the body’s ability to produce clotting factors.

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Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation 

MedicalResearch.com Interview with:

Professor Christopher P. Cannon MD Executive Director, Cardiometabolic Trials, Baim Institute Cardiologist Brigham and Women's Hospital Baim Institute for Clinical Research Columbia University College of Physicians and Surgeons

Dr. Cannon

Professor Christopher P. Cannon MD
Executive Director, Cardiometabolic Trials, Baim Institute
Cardiologist Brigham and Women’s Hospital
Baim Institute for Clinical Research
Columbia University College of Physicians and Surgeons

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The trial explored whether a dual therapy approach of anticoagulation and P2Y12 antagonist – without aspirin – in non-valvular atrial fibrillation (AF) patients following percutaneous coronary intervention (PCI) and stent placement would be as safe, and still efficacious, as the current standard treatment – triple therapy. For more detailed background on the study, readers may want to review the first paragraph of the article in the New England Journal of Medicine.

Results showed significantly lower rates of major or clinically relevant non-major bleeding events for dual therapy with dabigatran, when compared to triple therapy with warfarin.

In the study, the risk for the primary safety endpoint (time to major or clinically relevant non-major bleeding event) was 48 percent lower for dabigatran 110 mg dual therapy and 28 percent lower for dabigatran 150 mg dual therapy (relative difference), with similar rates of overall thromboembolic events.

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COMPASS Study Finds Rivaroxaban -XARELTO® – Plus Aspirin Reduces Adverse Events in Patients With Heart Disease or PAD

MedicalResearch.com Interview with:

John Eikelboom MBBS Associate Professor, Division of Hematology & Thromboembolism Department of Medicine Canada Research Chair in Cardiovascular Medicine Canadian Institutes for Health Research McMaster University

Dr. Eikelboom

John Eikelboom MBBS
Associate Professor, Division of Hematology & Thromboembolism
Department of Medicine
Canada Research Chair in Cardiovascular Medicine
Canadian Institutes for Health Research
McMaster University

MedicalResearch.com: What is the background for this study?

Response: Cardiovascular disease affects 1 in 25 persons around the world and a total of more than 300 million individuals. Thrombus formation at the site of a ruptured atherosclerotic plaque is the commonest mechanism of myocardial infarction and ischemic stroke in patients with cardiovascular disease. Aspirin is effective for the prevention of these complications but reduces the risk by only 19% during long term therapy.

Rivaroxaban has previously been tested in the ATLAS ACS-2 TIMI 51 trial at doses of 2.5 mg twice daily or 5 mg twice daily on top of background antiplatelet therapy and has been shown to reduce major adverse cardiovascular events as well as mortality. We tested these same doses of rivaroxaban for the prevention of cardiovascular death, stroke or myocardial infarction in patients with stable cardiovascular disease.

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Duration of Dual Anti-Platelet Therapy After Cardiac Stenting Needs To Be Personalized

MedicalResearch.com Interview with:
Abhishek Sharma MD and

Division of Cardiovascular Medicine State University
New York Downstate Medical Center
Dr.Sahil Agarwal M.B.B.S., M.D.
Division of Cardiology
St. Luke’s University Health Network
Bethlehem, Pennsylvania

MedicalResearch.com: What is the background for this study? 

Response: Prior randomized control trials (RCTs) and meta-analysis of these trials which have attempted to compare differences in outcomes between strategies of short (S) (3-6 months) and longer (L) (12-30 months) durations of dual anti-platelet therapy (DAPT) after drug eluting stents (DES) implantation have reported conflicting results. In general, the events rates in these studies were small, affecting statistical power. To overcome this limitation, we conducted an updated meta-analysis to compare the efficacy and safety of strategies of S-DAPT versus L-DAPT strategy after DES implantation by restricting inclusion to randomized studies with follow-up durations of 24 months or longer.

The current meta-analysis is the first to compare outcomes between S-DAPT and L-DAPT in a meta-analysis restricted to trials with patient follow-up of 24 months or longer. We found no significant difference in the rates of mortality or of stent thrombosis with S-DAPT or L-DAPT. S-DAPT was associated with significantly lower risk of major bleeding but slightly higher risk of future myocardial infarctions.

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Comparison of NOACs with Warfarin In Atrial Fibrillation Patients With Single Stroke Risk Factor

MedicalResearch.com Interview with:

Gregory Y. H. Lip, MD Professor of Cardiovascular Medicine University of Birmingham, UK; Adjunct Professor of Cardiovascular Sciences, Thrombosis Research Unit, Aalborg University, Denmark National Institute for Health Research (NIHR) Senior Investigator. Visiting Professor of Haemostasis Thrombosis & Vascular Sciences, Aston University, Birmingham, UK Visiting Professor of Cardiology, University of Belgrade, Serbia; Visiting Professor, University of Leeds, UK Honorary Professor, Chinese PLA Medical School, Beijing, China; Honorary Professor, Nanjing Medical University, Nanjing, China; Visiting Professor, National Yang-Ming University, Taipei, Taiwan Institute of Cardiovascular Sciences City Hospital Birmingham England UK

Dr. Lip

Gregory Y. H. Lip, MD
Professor of Cardiovascular Medicine
University of Birmingham
Adjunct Professor of Cardiovascular Sciences, Thrombosis Research Unit, Aalborg University, Denmark
National Institute for Health Research (NIHR) Senior Investigator.
Visiting Professor of Haemostasis Thrombosis & Vascular Sciences, Aston University, Birmingham, UK
Institute of Cardiovascular Sciences
City Hospital
Birmingham England UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The randomized clinical trials comparing non-Vitamin K antagonist oral anticoagulants (NOACs) vs warfarin largely focused on recruitment of high risk atrial fibrillation(AF) patients with >2 stroke risk factors, with only the trials testing dabigatran or apixaban including a minority of patients with 1 stroke risk factor.

Despite this, regulatory approvals of all NOACs have been for stroke prevention in AF patients with ≥1 stroke risk factors. No difference between NOACs compared to warfarin in risk of ischemic stroke/systemic embolism, was seen but for ‘any bleeding’, this was lower for apixaban and dabigatran compared to warfarin.

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Patients With Paroxysmal Atrial Fibrillation Less Likely To Receive Anticoagulants

MedicalResearch.com Interview with:

Dr Nicola Adderley BA, MSci (Cantab), MA, MPhil, PhD Institute of Applied Health Research Research Fellow University of Birmingham

Dr. Adderley

Dr Nicola Adderley BA, MSci (Cantab), MA, MPhil, PhD
Institute of Applied Health Research
Research Fellow
University of Birmingham

MedicalResearch.com: What is the background for this study?

Response: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major global public health problem. It is associated with a five-fold increase in risk of stroke.

There are three types of AF – paroxysmal, persistent or permanent. In paroxysmal AF, episodes come and go, and usually stop without any treatment. With persistent AF episodes can last for periods of more than seven days and are treated with medication or a medical procedure called cardioversion. In permanent AF, the irregular heartbeat is present all the time and cardioversion has failed to restore a normal heart rhythm.

All patients with AF, including paroxysmal AF, are at an increased risk of stroke. UK guidelines recommend anticoagulant treatment, such as the blood-thinning drug warfarin, for patients with all types of AF in order to reduce the risk of stroke.

Our study aimed to determine whether patients with paroxysmal AF are less likely to be treated with anticoagulants than patients with persistent or permanent AF and to investigate trends in treatment between 2000 and 2015.

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Anticoagulation With Bivalirudin vs Heparin for STEMI treated with PCI: Pros and Cons of Each

MedicalResearch.com Interview with:

Dr. Ion S. Jovin, MD, ScD Associate Professor of Medicine at Virginia Commonwealth University Pauley Heart Center Director of the Cardiac Catheterization Laboratories and Site Director of the VCU Interventional Cardiology Fellowship Program at  McGuire V.A. Medical Center Visiting Assistant Professor in the Department of Surgery/Cardiothoracic Surgery Yale University, New Haven, CT

Dr. Jovin


Dr. Ion S. Jovin, MD, ScD

Associate Professor of Medicine at Virginia Commonwealth University Pauley Heart Center
Director of the Cardiac Catheterization Laboratories and
Site Director of the VCU Interventional Cardiology Fellowship Program at
McGuire V.A. Medical Center
Visiting Assistant Professor in the Department of Surgery/Cardiothoracic Surgery
Yale University, New Haven, CT

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There is still uncertainty regarding the best anticoagulant for patients with acute ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI) and especially PCI done via radial (as opposed to femoral) access. Our study compared outcomes of patients with STEMI treated with PCI done via radial access in the NCDR database who received one of the two main anticoagulants: bivalirudin and heparin. There is a large degree of variation in the use of the two anticoagulants in PCI and in primary PCI both within the United States but also in the world.

We did not find a statistically significant difference between the outcomes of the two groups of patients, but we also found that a significant number of patients in both the heparin and in the bivalirudin group were also treated with additional medicines that inhibit platelet activation (glycoprotein IIb/IIIa inhibitors).

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Dabigatran is Associated With a Lower Risk of Osteoporotic Fractures Compared to Warfarin

MedicalResearch.com Interview with:
Wallis CY Lau BSc

Centre for Safe Medication Practice and Research
Department of Pharmacology and Pharmacy
Li Ka Shing Faculty of Medicine
The University of Hong Kong

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Warfarin is a vitamin K antagonist (VKA) oral anticoagulant used for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), a common heart rhythm disorder. It works by interfering with vitamin K-dependent reactions in the process of blood clot formation. As these reactions also play a role in bone mineralization, there is concern that warfarin use may be linked with osteoporotic fracture. Despite the concerns for fracture risk, warfarin had been an inevitable treatment choice for over 50 years as there were no other alternatives available.

Dabigatran is the first non-VKA oral anticoagulant (NOAC) approved for use in patients with NVAF. Recently, an animal study reported that use of dabigatran is associated with a better bone safety profile compared to warfarin in rats, suggesting a potential for a lower risk of osteoporotic fractures over warfarin. However, the actual risk of osteoporotic fractures with dabigatran use in human remains unclear. Therefore, we conducted a population-based cohort study to compare the risk of osteoporotic fractures in patients with NVAF treated with dabigatran and warfarin.

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High risks of mortality following bleeding and ischemic events occurring 1 year after coronary stenting

MedicalResearch.com Interview with:

Eric A. Secemsky, MD, MSc Interventional Cardiology Fellow Massachusetts General Hospital Harvard Medical School Baim Institute for Clinical Research

Dr. Eric Secemsky

Eric A. Secemsky, MD, MSc
Interventional Cardiology Fellow
Massachusetts General Hospital Harvard Medical School
Baim Institute for Clinical Research 

MedicalResearch.com: What is the background for this study?  What are the main findings?

Response: We know from previous trials that continuing dual antiplatelet therapy longer than 12 months after coronary stenting decreases ischemic events, including spontaneous myocardial infarction and stent thrombosis. However, extending dual antiplatelet therapy is also associated with some increase in bleeding risk. For instance, in the DAPT Study, more than 25,600 patients were enrolled and received both aspirin and a thienopyridine antiplatelet drug (clopidogrel or prasugrel) for one year after stenting. Of these patients, 11,648 participants who had followed the study protocol and had no serious cardiovascular or bleeding events during that first year were then randomized to either continue with dual therapy or to receive aspirin plus a placebo for another 18 months. The overall findings of the DAPT study were that, compared with switching to aspirin only after one year, continuing dual antiplatelet therapy for a total of 30 months led to a 1.6 percent reduction in major adverse cardiovascular and cerebrovascular events – a composite of death, myocardial infarction, stent thrombosis and ischemic stroke – and a 0.9 percent increase in moderate to severe bleeding events.

The prognosis following early ischemic and bleeding events has previously been well described. However, data for events occurring beyond 1 year after PCI are limited. As such, we sought to assess the cumulative incidence of death following ischemic and bleeding events occurring among patients in the DAPT Study beyond 1 year after coronary stenting.

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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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Anticoagulation Bridge Therapy May Be Unnecessary For Low Risk Venous Thromboembolism Patients


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. Continue reading

Study Weighs Risks/Benefits of Oral Anticoagulation for Atrial Fibrillation in Hemodialysis Patients

Dr. Simonetta Genovesi MD Department of Health Science University of Milano-Bicocca, Monza Italy Nephrology Unit San Gerardo Hospital, Monza, ItalyMedicalResearch.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.
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JAMA Study Confirms Better Anticoagulation Choice After Myocardial Infarction

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.

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Study Highlights Unpredictable Anticoagulation With Warfarin

Winnie Nelson PharmD, MS, MBA Director, Health Economics & Outcomes Research Janssen PharmaceuticalsMedicalResearch.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.
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Anticoagulation in Chronic Kidney Disease Patients with Atrial Fibrillation

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.

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Monoclonal Idarucizumab Antibody May Reverse Dabigatran Anticoagulation

MedicalResearch.com Interview with:
Dr. Joanne van Ryn, PhD
Department of CardioMetabolic Disease Research
Boehringer Ingelheim GmbH & Co., Germany

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

Response: Idarucizumab is a humanized antibody fragment, or Fab, being investigated as a specific antidote to reverse the anticoagulant effect of dabigatran. Currently, there are no specific antidotes available for any of the newer oral anticoagulants, or NOACs, to complement the existing range of bleed management options during critical care situations. Idarucizumab is being developed to provide physicians with an additional therapeutic option they could consider should a patient require emergency intervention or if a patient experiences uncontrolled bleeding.

Pre-clinical studies indicated idarucizumab binds specifically to and inhibits dabigatran. Phase I data with idarucizumab in healthy volunteers demonstrated the potential of idarucizumab to achieve immediate, complete and sustained reversal of dabigatran-induced anticoagulation. In that placebo-controlled study, idarucizumab did not cause any clinically relevant side effects.

This phase I sub-study in 35 healthy volunteers showed that idarucizumab restores dabigatran-induced inhibition of fibrin formation at a small wound site. Fibrin, the main component of a blood clot, was assessed by measuring levels of fibrinopeptide A (FPA), a substance that is released when fibrin is formed. Fibrin formation was assessed after a small scratch, similar to a paper cut, was made. Measurements were conducted at baseline, after administration of dabigatran, and after subsequent administration of idarucizumab or placebo. The results showed that dabigatran almost completely inhibited the production of FPA at the wound site, and that idarucizumab restored FPA production:

  • At baseline, before the volunteers took dabigatran, the average level of FPA was 3981 ng/mL.
  • On day three, 2.5 hours after the volunteers took dabigatran, the average level of FPA was 208 ng/mL, an approximate 95 percent decrease compared to baseline.
  • On day four, 2.5 hours after the volunteers took dabigatran and 30 minutes after they were infused with 1 g, 2 g or 4 g of idarucizumab, FPA levels were 24 percent, 45 percent and 95 percent, respectively, of the average baseline level.

The restored fibrin production at the wound site after idarucizumab dosing with 2g or 4g also correlated with reversal of the dabigatran-anticoagulation activity in circulating blood.

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Dabigatran vs Warfarin in Non-Valvular Atrial Fibrillation

dr_John-SeegerMedicalResearch.com Interview with:
Dr. John Seeger
, PharmD, DrPH
Department of Medicine, Brigham and Women’s Hospital

Dr. Seeger: What is the background for this study? What are the main findings?

Response: This study is part of an ongoing research program initiated in 2013 to assess prescribing patterns and real-world safety and effectiveness of oral anticoagulants, including dabigatran, for the reduction of stroke risk. The study program is expected to run through the end of 2016. Boehringer Ingelheim and Brigham and Women’s Hospital are aiming to gather data from more than 100,000 U.S. NVAF patients.

Using a sequential matched cohort design, the safety and effectiveness of dabigatran compared to warfarin among patients with non-valvular atrial fibrillation (NVAF) receiving these medications in routine care settings can be assessed periodically. The interim findings at this stage come from 38,378 non-valvular atrial fibrillation patients in two health insurance databases, MarketScan (31,058 patients) and UnitedHealth (7,320 patients). The primary analysis follows patients from start of therapy until a switch or discontinuation of the anticoagulant, an outcome event, or disenrollment. The average follow-up was five months for patients in the dabigatran group and four months for those taking warfarin. The primary outcomes measured in the analysis are stroke and major hemorrhage.

Interim findings from the combined databases showed a 25 percent reduction in the rate of major hemorrhage (hazard ratio [HR] 0.75, 95 percent confidence interval [CI] 0.65-0.87, 354 vs. 395 events) and a 23 percent reduction in strokes (HR 0.77, CI 0.54-1.09, 62 vs 69 events) for dabigatran compared to warfarin among these patients with NVAF. The database-specific results indicate a reduction in the rate of major hemorrhage with dabigatran (MarketScan: HR 0.78, CI 0.67- 0.91; UnitedHealth: HR 0.56, CI 0.36-0.86). In the larger MarketScan database, dabigatran reduced the stroke rate by 36 percent (HR 0.64, CI 0.44-0.95), while in the smaller UnitedHealth database, stroke rates were not different between the two anticoagulants, as there were only 26 strokes in total which led to wide confidence intervals (HR=1.62, CI 0.72-3.66).
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Warfarin Dosing: Do Genotype-Based Algorithms Improve Outcomes?

MedicalResearch.com Interview with:
David Ldr_david_l_brown. Brown, MD, FACC
Professor of Medicine
Cardiovascular Division
Washington University School of Medicine
St. Louis, MO 63110

MedicalResearch: What are the main findings of the study?

Dr. Brown: This meta-analysis of randomized controlled trials showed that using a genotype-based warfarin dosing algorithm did not improve the process or outcomes of anticoagulation compared to using a clinical dosing algorithm.
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Extended Use of Dabigatran, Warfarin, or Placebo in Venous Thromboembolism

 Author Interview: Sam Schulman M.D., FRCPC(C) Professor, Division of Hematology and Thromboembolism, Department of Medicine Associate Professor, Medicine, Karolinska Institute, Stockholm, Sweden Director, Clinical Thromboembolism Program Hamilton Health Sciences, Hamilton General Hospital, Hamilton, OntarioMedicalResearch.com  Author Interview: Sam Schulman M.D., FRCPC(C)
Professor, Division of Hematology and Thromboembolism, Department of Medicine
Associate Professor, Medicine, Karolinska Institute, Stockholm, Sweden
Director, Clinical Thromboembolism Program Hamilton Health Sciences, Hamilton General Hospital, Hamilton, Ontario

MedicalResearch.com: What are the main findings of the study?

Response: Similar effect of dabigatran  as warfarin, 92% risk reduction compared to placebo. The risk of bleeding is reduced by almost 50% compared to warfarin but in comparison with placebo there is an increased risk of minor bleeding. No routine coagulation monitoring or dose adjustments are required, making the treatment convenient for patients and physicians.
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