Does Genetic Information Encourage Doctors to Switch Anticoagulation Medications?

MedicalResearch.com Interview with:

Thomas J. Povsic, MD, PhDInterventional CardiologistDuke Clinical Research InstituteDuke University School of MedicineDurham, North Carolina 

Dr. Povsic

Thomas J. Povsic, MD, PhD
Interventional Cardiologist
Duke Clinical Research Institute
Duke University School of Medicine
Durham, North Carolina 

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

Response: The background for this study is that it is unknown how mandatory reporting of CYP2C19 metabolizer status affects how doctors treat patients or to what degree provision of this information would affect choice of a P2Y12 inhibitor within a clinical trial.

As part of the GEMINI-ACS trial, all patients underwent CYP2C19 metabolizer testing.  This trial enrolled patients with a recent acute coronary syndrome and randomized them to aspirin or a low dose of rivaroxaban.  All patients were also to be treated with ticagrelor or clopidogrel, which was at the discretion of the investigator.  Investigators were given information regarding the CYP2C19 metabolizer status about a week after randomization.  Importantly prior to randomization, all investigators were asked how they expected to use this information, and then we followed what they actually did.

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Contact Allergic Reactions to Implanted Cardiac Devices

MedicalResearch.com Interview with:

Amber Reck Atwater, M.D.Dermatology Residency Program DirectorAssociate Professor of DermatologyDirector, Contact Dermatitis ClinicDuke Dermatology

Dr. Reck Atwater

Amber Reck Atwater, M.D.
Dermatology Residency Program Director
Associate Professor of Dermatology
Director, Contact Dermatitis Clinic
Duke Dermatology 

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

Response: We completed an evaluation of our Duke Dermatology patients who underwent patch testing for possible allergy to their cardiac devices – pacemakers and defibrillators.

From March 1, 2012 to September 15, 2017 we saw 11 patients with suspected allergy to their devices.  Concern for allergy, skin eruption, skin symptoms, and concern for infection were common. 73% of patients had erythema at their implant scars; pruritus and pain were also noted.  Six of our patients had relevant reactions, and the most common allergies were metals, silicone and rubber accelerators.  Continue reading

Atrial Fibrillation: Antithrombotic Therapy after Acute Coronary Syndrome or PCI

MedicalResearch.com Interview with:

Renato D. Lopes MD, MHS, PhD Duke University Medical Center Duke Clinical Research Institute Durham, NC 27705

Dr. Renato Lopes

Renato D. Lopes MD, MHS, PhD
Professor of Medicine
Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute

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

Response: In patients with acute coronary syndromes (ACS), approximately 20% to 30% of those with nonvalvular atrial fibrillation (NVAF) have concomitant coronary artery disease (CAD), and 5 to 10% of patients who undergo PCI have NVAF. These patients often receive both antiplatelet therapy and oral anticoagulants; and how best to combine these agents to minimize bleeding risk without compromising protection against thrombosis is an important unanswered question.

Analysis of results for bleeding indicated no significant interaction between the two randomization factors permitting independent analysis of results for the two key comparisons. The first showed that apixaban was both non-inferior and significantly superior to VKA for the primary outcome with a 31% reduction in the relative risk for bleeding. Aspirin significantly increased the relative risk for bleeding versus placebo by 89%.

Results for the composite of death and hospitalization showed that apixaban resulted in a relative risk reduction of 17%, primarily driven by a reduction in all cause hospitalization. There was no significant difference between results for aspirin versus placebo for this outcome.

Analysis of the composite of death and ischemic events indicated no significant differences in results for apixaban versus VKA or aspirin versus placebo.

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Most Cardiovascular Guidelines Not Supported By Randomized Clinical Trials

MedicalResearch.com Interview with:
Renato D. Lopes MD, MHS, PhD
Professor of Medicine
Division of Cardiology
Duke University Medical Center
Duke Clinical Research Institute

Alexander C. Fanaroff, MD, MHS
Division of Cardiology and Duke Clinical Research Institute
Duke University, Durham, North Carolina

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

Response: About ten years ago, a group of researchers examined the evidence supporting guideline recommendations in cardiology for the first time. Quite surprisingly, they found that only 11% of recommendations in American College of Cardiology/American Heart Association (ACC/AHA) guidelines were supported by evidence from randomized controlled trials, the highest level of evidence. The researchers called for greater collaboration among investigators and funders in identifying key research questions, development of streamlined clinical trial methods, and expansion of funding for clinical research. Over the past 10 years, some of these steps have been taken, but it is unclear how the evidence supporting guideline recommendations has changed.

We therefore analyzed the 51 current cardiovascular guideline documents — 26 from the ACC/AHA and 25 from the European Society of Cardiology (ESC) — including 6,329 recommendations.

Overall, 8.5% of recommendations in ACC/AHA guidelines and 14.3% of recommendations in ESC guidelines were supported by evidence from randomized controlled trials. When looking specifically at guidelines that have been updated, we found no significant changes in the proportion of recommendations supported by evidence from randomized controlled trials.

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Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health

MedicalResearch.com Interview with:
John W. Stanifer, MD MSc
Duke Health

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

Response: The key take home for me is that Perfluorinated Chemicals (PFAS) are a globally ubiquitous pollutant with high human exposure and concerning chemical properties that appear to be capable of kidney kidney disease through several plausible different mechanisms; yet, we know almost nothing about long term kidney health outcomes, who is at greatest risk for adverse outcomes, or which communities may be most negatively impacted.

The original impetus for the study was the discovery of GenX in the drinking water of Wilmington NC, a pollutant from a company upstream (see: https://www.newsobserver.com/news/politics-government/state-politics/article199846619.html ). It has been a huge story in NC and every day more and more is being discovered about how pervasive the pollution has become (https://www.usnews.com/news/best-states/north-carolina/articles/2017-12-05/genx-compound-now-detected-in-food-product-in-n-carolina). While this was what caught my attention, as a North Carolinian, I quickly realized that these news stories are all over the place as any quick google search will reveal towns and communities contaminated with these from truly all of the United States. As a health disparities researcher in kidney disease,

I have been studying disparate rural populations in North Carolina, including American Indians, who live in communities with exceptionally high rates of kidney disease, which does not appear to be fully explained by “traditional” risk factors alone such as diabetes, hypertension, obesity, etc. So with that context in mind, I really have begun to focus on these chemicals as potential second-hits or augmenters of kidney disease; we have been doing preliminary studies, in which we have found them in the serum of individuals from these areas, but before we can go further, we really needed to understand what all is known about them and the plausibility that they could cause kidney disease. Therefore, we conducted this comprehensive study to characterize what the potential mechanisms between these chemicals and kidney disease are and where the biggest gaps are.

MedicalResearch.com: Were you surprised by any of the findings?

Response: I was actually surprised by a few things about it. I thought that the link between these chemicals and kidney disease would be pretty weak, with very little to suggest these could be primary drivers of kidney disease. And while the epidemiological studies provided conflicting evidence that mostly but not overwhelmingly pointed toward an association, the toxicology and pharmacokinetic studies demonstrated several key mechanisms that could explain how these chemicals cause kidney disease, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2– related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling.

It was also very interesting to learn that these compounds are taken up by the very same proximal tubule transporters that several known nephrotoxic drugs are taken up, including most notably the herb Aristocholic Acid which was of course responsible for the Balken Endemic Nephropathy that perplexed everyone for so long.

MedicalResearch.com: What recommendations do you have for future research as a result of this work? 

Response: Many gaps still exist. The biggest ones to me are that there are literally 1000s of these compounds, with only slight chemical variations, which make detection and regulation challenging. In fact most are still under proprietary aegis which prevents any type of study on them, and several of the “alternative” or “newer” PFCs (e.g. GEnX) have chemical properties that are particularly concerning, despite being marketed as “less toxic”. It is also very concerning to me that children and adolescents have the highest exposure; yet the long-term consequences are completely unknown and life-course epidemiology studies are very much needed. Finally, in the context of kidney disease, these are like so many other environmental toxins in that we don’t know how they interact to worsen or augment kidney disease in people with other risk factors such as diabetes or hypertension. So for example, wonder if you have diabetic nephropathy and are being exposed to these in high quantities? What does that mean for disparities in kidney disease and outcomes??

None of the authors have any disclosures with regards to this work.

 

Citation:

Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health
A Scoping Review

John W. Stanifer, Heather M. Stapleton, Tomokazu Souma, Ashley Wittmer, Xinlu Zhao and L. Ebony Boulware

CJASN September 2018, CJN.04670418; DOI: https://doi.org/10.2215/CJN.04670418 

Sep 19, 2018 @ 2:20 pm 

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