Phase 3 Study Finds XARELTO® Superior to Aspirin for Long-Term Prevention of Recurrent Blood Clots in VTE

MedicalResearch.com Interview with:

Paul Burton, MD, PhD, FACC Vice President, Medical Affairs Janssen

Dr. Paul Burton

Paul Burton, MD, PhD, FACC
Vice President, Medical Affairs
Janssen

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

Response: Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), affects more than 900,000 Americans each year; one-third of these occurrences are fatal. Once a person experiences a VTE, they are at risk of having another occurrence. Guidelines currently recommend anticoagulant therapy with a non-vitamin K antagonist oral anticoagulant (NOAC), like XARELTO® (rivaroxaban), for three months or longer. Once anticoagulant therapy is stopped, up to 10 percent of people will experience a recurrence during the first year and up to 20 percent within three years. In people who decide to stop anticoagulant therapy, guidelines currently suggest using aspirin for long-term prevention of recurrent VTE rather than no aspirin at all.

The Phase 3 EINSTEIN CHOICE study was designed to compare the efficacy and safety of XARELTO® to aspirin for continued VTE management in people who experienced an initial VTE. The study met its primary endpoint, finding both XARELTO® doses (10 mg or 20 mg once daily) to be superior to aspirin 100 mg once daily in preventing recurrent VTE, with no significant impact on safety. Specifically, XARELTO® 10 mg reduced the risk of recurrent VTE by 74 percent and XARELTO® 20 mg by 66 percent. Rates of major bleeding were comparable and low across all treatment groups.

These results were presented at the American College of Cardiology’s 64th Annual Scientific Session (ACC.17) during a Joint ACC/Journal of American Medical Association Late-Breaking Clinical Trials session and published simultaneously in The New England Journal of Medicine.

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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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Instantaneous Wave-Free Ratio To Evaluate Coronary Artery Disease

MedicalResearch.com Interview with:

Matthias Götberg, MD, PhD Director Cardiac Cath Lab Department of Coronary Heart Disease Skane University Hospital- Lund Lund, Sweden

Dr. Matthias Götberg

Matthias Götberg, MD, PhD
Director Cardiac Cath Lab
Department of Coronary Heart Disease
Skane University Hospital- Lund
Lund, Sweden

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

Response: Cardiologists encounter patients with narrowing of the coronary arteries on a daily basis. They typically use visual estimation of the severity of narrowing when performing coronary angiography, but it is difficult to accurately assess, based on a visual estimation alone, whether a stent is needed to widen the artery and allow the blood to more freely.

FFR (Fractional Flow Reserve) is more precise tool and results in better outcomes than using angiography alone to assess narrowing of the coronary arteries. With FFR, the doctor threads a thin wire through the coronary artery and measures the loss of blood pressure across the narrowed area. To acquire an accurate measurement, the patient must be given adenosine, which is a drug that dilates the blood vessels during the procedure. This drug causes discomfort; patients describe having difficulty breathing or feeling as if someone is sitting on their chest. The drug also adds to the cost of the procedure and can have other rare but serious side effects.

iFR (Instantaneous Wave-Free Ratio) is also based on coronary blood pressure measurements using a thin wire, but unlike FFR, it uses a mathematical algorithm to measure the pressure in the coronary artery only when the heart is relaxed and the coronary blood flow is high. As a result, a vasodilator drug is not needed.
iFR has been validated in smaller trials and have been found to be equally good as FFR to detect ischemia, but larger randomized outcome trials are lacking.

iFR-Swedeheart is a Scandinavian Registry-based Randomized Clinical Trial (RRCT) in which 2000 patients were randomized between iFR and FFR as strategies for performing assessment of narrowed coronary vessels. The primary composite endpoint at 12 months was all-cause death, non-fatal myocardial infarction, and unplanned revascularization.
RRCT is a new trial design originating from Scandinavia using existing web-based national quality registries for online data entry, randomization and tracking of events. This allows for a very high inclusion rate and low costs to run clinical trials while ensuring robust data quality.

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TAVR for Bicuspid Vs. Tricuspid Aortic Valve Stenosis

MedicalResearch.com Interview with:
Sung-Han Yoon MD
Clinical Trials, Cardiology, Developmental Biology
Cedars-Sinai Medical Center, Los Angeles

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

Response: Transcatheter aortic valve replacement (TAVR) has become the standard treatment in inoperable patients in high surgical risk patients with symptomatic severe aortic stenosis (AS). However, major randomized trials excluded congenital bicuspid AS due to its unique morphological features. The indication of TAVR is expanding into a younger population, in which the frequency of bicuspid AS is higher. Therefore, we will encounter TAVR for bicuspid AS more frequently. However, the experience of TAVR in bicuspid AS is limited to small series. Therefore, we aim to evaluate the clinical outcomes of TAVR in bicuspid AS and compare them to tricuspid AS.

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iFR Can Assess Need For Coronary Revascularization Without Adenosine

MedicalResearch.com Interview with:

Dr. Justin Davies PhD Senior Reserch Fellow and Hononary Consultant Cardiologist National Heart and Lung Institute, Imperial College Londo

Dr. Davies

Dr. Justin Davies PhD
Senior Reserch Fellow and Hononary Consultant Cardiologist
National Heart and Lung Institute,
Imperial College London

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

Response: We know from the FAME study that compared to angiography alone, FFR guided revascularization improves long-term clinical outcomes for our patients. Despite this, adoption of FFR into everyday clinical practice remains stubbornly low. One major factor for this is the need for adenosine (or other potent vasodilator medications) in order to perform an FFR measurement. Adenosine is expensive, unpleasant for the patient, time consuming and even potentially harmful.

iFR is a newer coronary physiology index that does not require adenosine for its measurement. In the prospective, multi center, blinded DEFINE FLAIR study, 2492 patients were randomly assigned to either FFR guided revascularisation or iFR guided revascularization and followed up for a period of 1 year.
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Cannabis Users Have Increased Risk of Stroke and Heart Failure

MedicalResearch.com Interview with:

Aditi Kalla, MD Cardiology Research Fellow Einstein Medical Center, Philadelphia

Dr. Aditi Kalla

Aditi Kalla, MD
Cardiology Research Fellow
Einstein Medical Center
Philadelphia

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

Response: As of the recent 2016 election, decriminalization of cannabis passed in several states bringing the total count up to 28 states and D.C. where cannabis is now legal for medicinal and/or recreational purposes. From a physician’s perspective, it is rare that a drug has “hit the market” so to speak without undergoing clinical trials to determine safety and efficacy. Hence, we sought out to study if cannabis had any effects (positive or negative) on the cardiovascular system.

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Radiation Exposure and Vascular Access in Acute Coronary Syndromes: The RADMatrix Trial

MedicalResearch.com Interview with: Dr. Marco Valgimigli,

Dr. Marco Valgimigli

MedicalResearch.com Interview with:
Dr. Marco Valgimigli, MD, PhD

Interventional Cardiology
Sandro Pertini Hospital, ASL RM2, Rome, Italy

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

Response: Every year millions of people with coronary artery disease are treated worldwide with percutaneous coronary intervention (PCI). Radial access as compared to femoral access reduces bleeding and mortality in patients with acute coronary syndrome (ACS) undergoing invasive management. However, prior studies have raised concerns over the increased risk of radiation exposure for both patients and operators with radial instead of femoral access and it remains still unclear whether radial access increases the risk of operator or patient radiation exposure in contemporary practice when performed by expert operators.

The MATRIX (Minimizing Adverse Haemorrhagic Events by TRansradial Access Site and Systemic Implementation of angioX) trial is the largest randomized trial comparing radial versus femoral access in ACS patients undergoing invasive management. In this radiation sub-study (RAD-MATRIX), we collected fluoroscopy time and dose area product (DAP) and equipped radial operators consenting to participate with dedicated dosimeters, each wearing a thorax (primary endpoint), wrist and head (secondary endpoints) lithium fluoride thermo luminescent dosimeter, during study conduct to establish non-inferiority of radial versus femoral access.

Among eighteen operators, performing 777 procedures in 767 patients, the non-inferiority primary endpoint was not achieved. Operator equivalent dose at the thorax was significantly higher with radial than femoral access. After normalization of operator radiation dose by fluoroscopy time or DAP, the difference remained significant. Radiation dose at wrist or head did not differ between radial and femoral access. Thorax operator dose did not differ in the right radial compared to the left radial access. In the overall MATRIX population, fluoroscopy time and DAP were higher with radial as compared to femoral access.

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Cardiovascular Procedures That Push the Line: High-Risk or Futility of Care?

MedicalResearch.com Interview with:

Adam Skolnick, MD Cardiologist Associate professor of medicine NYU Langone Medical Center

Dr. Adam Skolnick

Adam Skolnick, MD
Cardiologist
Associate professor of medicine
NYU Langone Medical Center  

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

Response: I am privileged to serve on the ACC Program Planning Committee and helped to design this important session that seeks to determine the line between when a cardiovascular procedure is high risk and when it is futile.    I am co-chairing the session with the incoming chair of the section on Geriatric Cardiology for the ACC, Dr. Karen Alexander from Duke.

We are practicing medicine at one of the most extraordinary times when there are so many devices and procedures to prolong and improve quality of life.    It is critical to assess a patient’s goals of care for a given intervention.   In some patients, particularly those who are multiple degenerative chronic conditions, are frail and/or have cognitive impairment it is difficult to know when a given procedure multiple medical conditions will achieve a patient’s goals.   When is a procedure high risk, and when is it simply futile?    This is the fine line upon which many cardiologists often find themselves.

The speakers present case examples of high risk patients considering TAVI, high risk PCI or CABG and mechanical support devices and with interaction from the audience work through when each procedure is high risk and when it is unlikely to achieve a patient’s goals of care.   We also have a dedicated talk on high risk procedures in patients with cognitive impairment, such as advanced dementia.

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ST-Segment Elevation and Cardiac MRI in MI With Non-Obstructive Coronary Arteries

MedicalResearch.com Interview with:

Harmony Reynolds, MD Cardiologist and the Saul J. Farber Associate Professor of Medicine NYU Langone Medical Center

Dr. Reynolds

Harmony Reynolds, MD
Cardiologist
Saul J. Farber Associate Professor of Medicine
NYU Langone Medical Center

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

Response: Some patients with heart attack have open, rather than severely narrowed, coronary arteries when they have a heart attack. This type of heart attack, known as myocardial infarction with non-obstructive coronary arteries or MINOCA, can be caused by a number of different problems. Cardiac MRI is useful because it can help physicians to find the underlying cause of MINOCA.

MINOCA patients with ST elevation on the ECG are at higher risk of death than those without ST elevation but it is not known whether ST elevation correlates with any specific underlying cause of MINOCA.

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Effect of Moderate-Intensity Exercise Training on Peak Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy

MedicalResearch.com Interview with:

Sara Saberi, MD Assistant Professor Inherited Cardiomyopathy Program Frankel Cardiovascular Center University of Michigan Hospital and Health Systems

Dr. Sara Saberi

Sara Saberi, MD
Assistant Professor
Inherited Cardiomyopathy Program
Frankel Cardiovascular Center
University of Michigan Hospital and Health Systems 

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

Response: Patients with hypertrophic cardiomyopathy are often told not to exercise or to significantly curb their exercise due to concern over the potential risk of increased ventricular arrhythmias and sudden cardiac death. There is no data regarding risks/benefits of exercise in HCM though. There is, however, data that shows that patients with HCM are less active and more obese than the general population AND a majority feel that exercise restrictions negatively impact their emotional well-being.

So, we devised a randomized clinical trial of a 16-week moderate-intensity aerobic exercise program versus usual activity with the primary outcome being change in peak VO2 (oxygen consumption). This exercise intervention resulted in a 1.27 mL/kg/min improvement in peak VO2 over the usual activity group, a statistically significant finding. There were no major adverse events (no death, aborted sudden cardiac death, appropriate ICD therapies, or sustained ventricular tachycardia). There was also a 10% improvement in quality of life as measured by the Physical Functioning scale of the SF-36v2.

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Instantaneous Wave-free Ratio vs Fractional Flow Reserve to Guide PCI

MedicalResearch.com Interview with:

Dr. Matthias Götberg MD PhD Department of Cardiology, Clinical Sciences Lund University, Skåne University Hospital Lund, Sweden

Dr. Matthias Götberg

Dr. Matthias Götberg MD PhD
Department of Cardiology, Clinical Sciences
Lund University, Skåne University Hospital
Lund, Sweden

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

Response: Cardiologists encounter patients with narrowing of the coronary arteries on a daily basis. They typically use visual estimation of the severity of narrowing when performing coronary angiography, but it is difficult to accurately assess, based on a visual estimation alone, whether a stent is needed to widen the artery and allow the blood to more freely.

FFR (Fractional Flow Reserve) is more precise tool and results in better outcomes than using angiography alone to assess narrowing of the coronary arteries. With FFR, the doctor threads a thin wire through the coronary artery and measures the loss of blood pressure across the narrowed area. To acquire an accurate measurement, the patient must be given adenosine, which is a drug that dilates the blood vessels during the procedure. This drug causes discomfort; patients describe having difficulty breathing or feeling as if someone is sitting on their chest. The drug also adds to the cost of the procedure and can have other rare but serious side effects.

iFR (Instantaneous Wave-Free Ratio) is also based on coronary blood pressure measurements using a thin wire, but unlike FFR, it uses a mathematical algorithm to measure the pressure in the coronary artery only when the heart is relaxed and the coronary blood flow is high. As a result, a vasodilator drug is not needed.

iFR has been validated in smaller trials and have been found to be equally good as FFR to detect ischemia, but larger randomized outcome trials are lacking.

iFR-Swedeheart is a Scandinavian Registry-based Randomized Clinical Trial (RRCT) in which 2000 patients were randomized between iFR and FFR as strategies for performing assessment of narrowed coronary vessels. The primary composite endpoint at 12 months was all-cause death, non-fatal myocardial infarction, and unplanned revascularization.

RRCT is a new trial design originating from Scandinavia using existing web-based national quality registries for online data entry, randomization and tracking of events. This allows for a very high inclusion rate and low costs to run clinical trials while ensuring robust data quality.  Continue reading