Praluent May Reduce Need For Apheresis In Some Patients With Familial Hypercholesterolemia

MedicalResearch.com Interview with:

Dr. Jay Edelberg VP Head of CV Development and Head Global CV Medical Affairs

Dr. Edelberg

Dr. Jay Edelberg MD, PhD
VP Head of CV Development and
Head Global CV Medical Affairs
Sanofi 

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

Response: Patients with heterozygous familial hypercholesterolemia (HeFH) are often not able to achieve their target low-density lipoprotein cholesterol (LDL-C) levels, and some may require lipoprotein apheresis (LA) to lower their “bad cholesterol.” Apheresis is a procedure similar to kidney dialysis, where bad cholesterol is mechanically removed from the blood. It is an invasive, expensive, and time-consuming treatment for patients, as well as physicians.

The Phase III ESCAPE clinical study looked at the potential effect of LA on total Praluent, free and total PCSK9 concentrations, as well as the combined pharmacodynamics effect of total Praluent on LDL-C-lowering.

Praluent levels remained unaffected by apheresis, and Praluent consistently suppressed free PCSK9 levels in patients with HeFH, regardless of LA treatment. This analysis further confirms clinical ESCAPE data that Praluent can be used in conjunction with LA and may reduce or potentially eliminate the need for LA in some patients.

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Lack of Response to LDL-Lowering Praluent Rare

MedicalResearch.com Interview with:

Dr. Jay Edelberg VP Head of CV Development and Head Global CV Medical Affairs

Dr. Edelberg

Dr. Jay Edelberg MD, PhD
VP Head of CV Development and
Head Global CV Medical Affairs
Sanofi

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

Response: Clinical trials of lipid-lowering therapies (LLTs), including statins, often report variations in treatment response regarding effects on low density-lipoprotein cholesterol (LDL-C) levels, although LDL-C reductions are fairly consistent between trials. Praluent is generally well tolerated, however hyporesponsiveness exists in few patients.

Potential causes for variation in patient responsiveness to Praluent include lack of receipt of active study drug, changes in concurrent LLTs, inaccurate or unrepresentative baseline lipid levels, concurrent acute-phase illness, and biological nonresponsiveness.

This analysis evaluated patients pooled from 10 ODYSSEY trials to assess characteristics of patients with hyporesponsiveness to Praluent, defined as <15% LDL-C reduction from baseline at all analyzed time points.

Overall, only 1% of patients (n=33) had <15% LDL-C reduction at all time points. Prolonged hyporesponsiveness to Praluent was rarely associated with Praluent antidrug antibodies. Of the 33 patients with <15% LDL-C reduction at all study timepoints, 27 had undetectable or missing alirocumab levels, absence of pharmacokinetics analyses, or early treatment discontinuation.

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Verseon’s Precision Anticoagulants Prevent Clotting Without Excess Bleeding Risk in Preclinical Studies

MedicalResearch.com Interview with:
https://www.verseon.com/
Anirban Datta, PhD

Director Discovery Biology
Verseon Corporation


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

Response: Today’s anticoagulant market is dominated by the NOACs. These oral anticoagulants require less constant monitoring and have reduced drug and food interactions compared to their predecessors, warfarin and heparin. However, there is still a significant bleeding risk associated with the NOACs. This is particularly problematic when they are co-dosed with antiplatelet drugs. While life-long therapy combining an oral anticoagulant with one or two antiplatelet drugs is desired for the many patients suffering from both non-valvular atrial fibrillation and coronary artery disease, current treatment guidelines limit such therapy to a maximum of six months to a year due to safety concerns.

At Verseon, we are developing a novel class of precision anticoagulants that combine efficacy comparable to the NOACs with a significantly reduced bleeding risk in preclinical testing. We believe that this profile can have a positive impact on the lives of the many patients in need of long-term anticoagulation-antiplatelet combination therapy.

We are currently advancing two development candidates toward clinical trials in 2018. VE-1902, our first development candidate, is scheduled to enter phase I in the first half of the year. Continue reading

Idarucizumab – Praxbind – Reverses Anticoagulant Effect of Pradaxa Prior To Emergency Surgery

MedicalResearch.com Interview with:

Thomas Seck, M.D., vice president Clinical Development and Medical Affairs, Primary Care Boehringer Ingelheim Pharmaceuticals, Inc.

Dr. Thomas Seck

Thomas Seck, M.D., vice president
Clinical Development and Medical Affairs
Primary Care
Boehringer Ingelheim Pharmaceuticals, Inc.

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

Response: This is a new subanalysis of the phase III RE-VERSE AD™ study, which evaluated the safety and efficacy of idarucizumab, marketed in the U.S. as Praxbind®, in reversing the anticoagulant effect of Pradaxa® (dabigatran etexilate mesylate). This data assessed idarucizumab in a subset of patients requiring an urgent procedure or emergency surgery.

The analysis found that idarucizumab rapidly and completely reversed the anticoagulant effect of dabigatran in approximately 98 percent of patients based on dTT. The median time between administration of idarucizumab and start of surgery was 1.7 hours for patients requiring abdominal procedures, 1.9 hours for orthopedic procedures, 1.4 hours for vascular procedures, 1.3 hours for drainage procedures and 1.2 hours for catheter procedures. Among these patients, periprocedural homeostasis was assessed as normal in more than 92 percent of patients, across all surgery types.

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Children and Young Adults With Diabetes Have Increased Risk of Sudden Cardiac Death

MedicalResearch.com Interview with:
“Diabetes Test” by Victor is licensed under CC BY 2.0Jesper Svane

Medical student
The Heart Center, University Hospital Rigshospitalet
Copenhagen 

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

Response: At the beginning of this research project, we were aware that persons with diabetes have an increased risk of death, which is partly explained by an increased risk of sudden cardiac death. However, previous studies on causes of death and mortality among young persons with diabetes, particularly type 2 diabetes, are sparse. Furthermore the incidence of sudden cardiac death among young persons with diabetes in a nationwide setting is unknown.

The main purpose of the study was to illuminate the risk of death and especially the risk of cardiac death among children/young adults with diabetes.

On a personal note, a friend of mine, who was healthy and fit, died suddenly a few years ago at the age of 19. This tragic death raised a lot of feelings as well as questions in me. When I got the chance to work with Dr. Lynge and Dr. Tfelt, I saw this as an opportunity to expand my knowledge of sudden cardiac death among the young. Furthermore, the opportunity of contributing to research in order to prevent these devastating events in the future was personally appealing to me.

I initiated the project together with Thomas Hadberg Lynge, MD, last year, with Jacob Tfelt-Hansen, MD, DMSc as supervisor. Both are experienced researchers within the field of sudden cardiac death. Dr. Tfelt-Hansen leads a very productive research group at Rigshospitalet, Copenhagen, whose main focus is arrhythmias and sudden cardiac death.

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AI Study Supports Association of Increased Coffee Consumption With Decreased CVD Risk

MedicalResearch.com Interview with:
Coffee being poured Coffee pot pouring cup of coffee.  copyright American Heart Association
Laura Stevens
University of Colorado
Aurora, CO

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

Response:
We started with asking ourselves how we could better predict cardiovascular and stroke outcomes.  In an ideal world, we would be able to predict cardiovascular disease (CVD) and stroke with 100% accuracy long before the occurrence of the event.  The challenge here is there are so many potential risk factors, and testing each one using traditional methods would be extremely time consuming, and possibly infeasible.

Therefore, we used artificial intelligence to find potential risk factors that could be important for risk of CVD and stroke.  The results of this analysis pointed to consumption of coffee cups per day and the number of times red meat was consumed per week as being potentially important predictors of CVD.

We then looked into these findings further using traditional statistical analyses to determine that increased coffee consumption and red meat consumption appeared to be associated with decreased risk of CVD.  The study initially used data from the Framingham Heart Study (FHS) original cohort.

The findings from this data were then tested using data from 2 independent studies, the Cardiovascular Heart Study (CHS) and the Atherosclerosis Risk in Communities Study (ARIC), which both supported the association of increased coffee consumption with decreased CVD risk.

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Benefits of Hypertension Treatment Depends Somewhat on Starting Blood Pressure Level

MedicalResearch.com Interview with:

Blood pressure monitor reading 120/80 copyright American Heart Association

Blood pressure monitor reading 120/80
copyright American Heart Association

Dr. Mattias Brunström
Department of Public Health and Clinical Medicine
Umeå University,Sweden

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

Response: Current guidelines recommend a systolic blood pressure treatment target below 140 mm Hg for most people. Since the publication of SPRINT however, many have suggested guidelines should be changed, recommending further blood pressure lowering.

We performed a systematic review and meta-analysis of randomized clinical trials comparing different blood pressure targets or antihypertensive treatment verus placebo. We separated primary preventive trials from secondary preventive trials, and stratified primary preventive trials by mean baseline systolic blood pressure. The analyses included 74 trials, with in total > 300 000 participants. Interestingly, we found that treatment effect was dependent on baseline systolic blood pressure in people without previous CVD.

While primary preventive treatment reduced the risk of death and cardiovascular disease if systolic blood pressure was 140 mm Hg or higher, treatment effect was neutral if systolic blood pressure was below 140 mm Hg.

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High-Sensitivity Cardiac Troponin I Can Identify Low Risk Chest Pain Patients

MedicalResearch.com Interview with:

Dr Andrew R. Chapman BHF Clinical Research Fellow University of Edinburgh Chancellors Building Edinburgh 

Dr. Chapman

Dr Andrew R. Chapman
BHF Clinical Research Fellow
University of Edinburgh
Chancellors Building
Edinburgh 

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

Response: High-sensitivity cardiac troponin tests allow accurate measurement of cardiac troponin in the bloodstream. Currently, guidelines recommend we evaluate patients with suspected myocardial infarction using these tests, by looking for levels which are above the upper reference limit (99th centile). These troponin measurements are taken on arrival, and often repeated after admission to hospital up to six hours later. When levels are below this limit, the diagnosis of myocardial infarction is ruled out. However, using such a high limit in patients on arrival to hospital may not be safe, as lower risk stratification thresholds has been shown to reduce missed events,  and in these patients admission to hospital for repeat testing may not be necessary. However, there is no consensus as to the optimal threshold for use in practice.

In a worldwide study of 23,000 patients from 9 countries, we have shown when high-sensitivity cardiac troponin I concentrations are below a risk stratification threshold of 5 ng/L at presentation, patients are at extremely low risk of myocardial infarction or cardiac death at 30 days, with fewer than 1 in 200 patients missed. Importantly, this threshold identifies almost 50% of all patients as low risk after a single blood test. As admission or observation of these patients is estimated to cost as much as $11 billion per year in the United States, this strategy has major potential to improve the efficiency of our practice.

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TESLA Car May Not Trip Your Defibrillator

MedicalResearch.com Interview with:

Abdul Wase MD FACC FACP FHRS Clinical Professor of Medicine & Director, Cardiology Fellowship Program, Wright State University Boonshoft School of Medicine, Director, Electrophysiology Laboratories Good Samaritan Hospital, Dayton, OH 

Dr. Wase

Abdul Wase MD FACC FACP FHRS
Clinical Professor of Medicine &
Director, Cardiology Fellowship Program,
Wright State University Boonshoft School of Medicine,
Director, Electrophysiology Laboratories
Good Samaritan Hospital,
Dayton, OH

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

Response: Implantable cardiac defibrillators (ICD) patients are subject to electromagnetic interferences (EMI) from outside electrical sources.

TESLA electric vehicle has a large battery underneath the surface of vehicles, which may potentially interfere with the functioning of these devices. In the owner’s manual, TESLA warns that using mobile connector may impair the functioning of implantable pacemaker or a defibrillator.

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Eating a Mostly Plant Based Diet Linked To Lower Risk of Heart Failure

MedicalResearch.com Interview with:
“Fresh Food” by Sonny Side Up! is licensed under CC BY 2.0

 

Dr. Kyla M Lara
Icahn School of Medicine at Mount Sinai

 

 

 

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

Response: This was the first study to evaluate whether dietary patterns of black and white adults living in the United States were associated with developing heart failure. We’re hearing a lot in the news about specific diets like low-fat, high protein, low carb, and other diets that decrease cardiovascular risk. We would love it, as physicians, if we could prescribe a specific diet to limit cardiovascular risk in our patients. I’m really excited about our study because instead of examining patterns of what we already know are healthy, we looked at foods people were regularly consuming in the United States and developed dietary patterns from this. This study is similar to other work we have done with stroke and heart attack.

We used data from the NIH funded REGARDS study, also known as the Reasons for Geographic and Racial Differences in Stroke. More than 30,000 white and African-American adults were recruited from 2003-2007. From this group, we studied over 18,000 adults who successfully completed a dietary assessment called the Food Frequency Questionnaire. This was a really great group to study because people who live in this particular geographic area of the Southeastern United States, also known as the stroke belt, suffer from a higher risk of death from stroke. It’s extremely important for us to better understand the major risk factors that contribute to this and also cardiovascular disease.

We used statistical techniques to derive 5 dietary patterns based on the types of foods participants tended to eat.
• Convenience – Mexican and Chinese food, mixed dishes (both meat and bean)
• Sweets – added fats, bread, chocolate, desserts, sweet breakfast foods
• Southern – added fats, fried food, organ and processed meat, fatty milk
• Alcohol/Salads – beer, wine, liquor, green leafy vegetables, salad dressings, nuts and seeds, coffee
• Plant Based- fruit, vegetables, fruit juice, cereal, fish, poultry

Each participant received a score for each pattern that reflected how closely their diet resembled that dietary pattern. This approach reflects the real world and how people eat.

Over the 3135 days (8.6 years) of median follow up, 594 participants were hospitalized for incident HF. Greatest adherence to the plant-based dietary pattern during the study period was associated with a 28% risk reduction of developing heart failure.
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