Trial To Test Effect of Aspirin on Progression of Kidney Disease in Diabetes

MedicalResearch.com Interview with:
Francesco Violi MD
Department of Internal Medicine and Medical Specialties e Sapienza University
Rome, Italy

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

Response: The paper reports on the protocol of a trial where we will test the effect of aspirin on renal disease progression in diabetic patients. The study will start shortly and will be terminate next year.

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Aspirin Desensitization in Patients With Coronary Artery Disease

MedicalResearch.com Interview with:

Roberta Rossini, MD, PhD USC Cardiologia, Cardiovascular Department Bergamo, Italy

Dr. Rossini

Dr. Roberta Rossini, MD, PhD
USC Cardiologia, Cardiovascular Department
Bergamo, Italy 

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

Response: Aspirin (ASA) is stilll the cornerstone of antithrombotic therapy in patients with coronary artery disease, especially after PCI, both

in the acute and the chronic phase of treatment. However, ≈2% of patients have hypersensitivity to ASA. ASA desensitization may represent a valid approach. Desensitization protocols generally involve gradual increases in patient exposure to ASA with the goal of mitigating or abolishing immune-mediated reaction. However, many desensitization protocols require several days to be completed, making them unpractical. This may also contribute to the limited experience with applying ASA desensitization protocols in real-world practice in patients with CAD.

We previously reported the results of a pilot investigation supporting the feasibility of performing a rapid (<6 hours)

Aspirin desensitization protocol in patients undergoing PCI with stent implantation (Rossini R, Angiolillo DJ, Musumeci G, Scuri P, Invernizzi P, Bass TA, Mihalcsik L, Gavazzi A. Aspirin desensitization in patients undergoing percutaneous coronary interventions with stent implantation. Am J Cardiol. 2008;101:786–789. doi: 10.1016/j.amjcard.2007.10.045). The encouraging findings from our pilot feasibility investigation prompted the design of a larger scale multicenter investigation aimed to assess the safety and efficacy of a rapid aspirin  desensitization protocol in patients with a history of ASA hypersensitivity undergoing coronary angiography.

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Stroke Prevention: No Advantage To Taking Three Blood Thinners After First Stroke

MedicalResearch.com Interview with:

Professor Philip Bath Stroke Association Professor of Stroke Medicine/Head of Division of Clinical Neuroscience Faculty of Medicine & Health Sciences University of Nottingham

Prof. Philip Bath

Professor Philip Bath
Stroke Association Professor of Stroke Medicine/Head of Division of Clinical Neuroscience
Faculty of Medicine & Health Sciences
University of Nottingham 

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

Response: Blood thinning (antiplatelets) drugs reduce further strokes (recurrence) after stroke and mini-stroke (TIA). One antiplatelet, such as aspirin, is better than none, and two different drugs are better than one. The question then is whether three would be better still, providing excess bleeding is not problematic.

3096 patients with ischaemic stroke (stroke due to a blood clot) or mini-stroke were enrolled within 48 hours. They were randomised to take intensive separate antiplatelet therapy (three drugs comprising aspirin, clopidogrel and dipyridamole) or guideline therapy (either clopidogrel alone, or combined aspirin and dipyridamole) for 30 days (after which they took guideline treatment). At 90 days we assessed whether patients had had another stroke or mini-stroke, and how dependent or disabled this had left them.

There were slightly fewer recurrent strokes and mini-strokes between intensive and guideline treatment but the difference was not different statistically, so a neutral trial. In contrast, major bleeding was significantly increased in the intensive group as compared with guideline treatment. When looking at the net benefit/harm, there was no difference between the treatment groups.

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Aspirin Promotes Growth of Staph aureus in Nose

MedicalResearch.com Interview with:
Dr. Fernanda Buzzola

IMPaM, UBA-CONICET

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

Response: Staphylococcus aureus represents a serious problem to public health due to methicillin-resistance and the bacterial persistence over a long period of time in the host. Approximately the 20% of the human population is at risk to acquire an endogenous infection by S. aureus as a consequence of its asymptomatic nasal colonization.

Aspirin, the main source of salicylic acid in the human host, is currently taken by millions of human beings worldwide without medical prescription and widely indicated for defined purposes, including prevention of coronary thrombosis. Salicylic acid is a plant hormone known too for its use as a key ingredient in anti-acne preparations and medications for skin conditions. We also consume mild doses of salicylic acid when we eat fruits and vegetables. Iron is an important trace element for the human body and plays an essential role in blood formation. The metabolism of many bacteria, including S. aureus, also depends on the availability of iron molecules. Salicylic acid forms complexes with iron ions in the blood and so deprives not only us but also the staphylococcal bacteria of this element. S. aureus modifies its metabolism if the iron content is insufficient. The microorganism reacts to the changed – from its perspective, negative – conditions through the intensified formation of a biofilm, a sort of layer of slime formed by the aggregation of individual bacteria. The enhanced biofilm production allows the bacteria to survive for an even longer period under unfavourable living conditions.

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Study Finds Aspirin Safe For People Waiting To Have Coronary Artery Surgery

MedicalResearch.com Interview with:

Professor Paul Myles MBBS, MPH, MD, FCARCSI, FANZCA, FRCA Director, Dept of Anaesthesia and Perioperative Medicine Alfred Hospital and Monash University, Melbourne, Australia

Prof. Paul Myles

Professor Paul Myles MBBS, MPH, MD, FCARCSI, FANZCA, FRCA
Director, Dept of Anaesthesia and Perioperative Medicine
Alfred Hospital and Monash University, Melbourne, Australia

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

Dr. Myles: When we set up this study 10 years ago there was marked variation in practice for  people taking aspirin waiting for coronary artery bypass surgery.  About half were being told that they must stop their aspirin 5-7 days before surgery, and the other half were told that they should stay on their aspirin. This variation existed across different countries, different cities, and even within a single hospital. Doctors had varied opinions because reliable medical research was sparse; the evidence was contradictory. We thus designed a definitive clinical trial in which half the patients were randomly assigned to receive aspirin and the other half received a placebo. Our study has shown that aspirin is safe (i.e. it does not increase the bleeding risk). We also found that there does not appear to be a benefit during and after surgery, but in view of the clear benefits that exist in daily life, including the preoperative waiting period, we recommend that people should stay on their aspirin if they are having coronary artery surgery.

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Is It Possible To Build A Better Aspirin?

Prof. Daniel Klessig Professor at Boyce Thompson Institute and Cornell University

Prof. Daniel Klessig

MedicalResearch.com Interview with:
Prof. Daniel Klessig
Professor at  Boyce Thompson Institute
and Cornell University

Medical Research: What is the background for this study?

Prof. Klessig: Acetyl salicylic acid, commonly called aspirin, has been the most widely used drug worldwide for more than a century. Currently, 80 million pounds of aspirin are produced worldwide every year and almost 30 billion tablets are consumed annually in the US alone. Long before German pharmacologist Johann Buchner identified the salicylic acid derivative salicin in 1828 as the ingredient in willow bark that is responsible for its therapeutic effects, different cultures throughout the world were, and many still are, using a variety of plants rich in salicylic acid derivatives, such as willow, wintergreen, and meadowsweet, to treat pain, fever, swelling, and other maladies. Aspirin also is used to reduce the risk of heart attack, stroke, and certain cancers.

One might expect that aspirin’s mechanisms of action would be well understood, given its extraordinarily widespread use and the fact that it was first synthesized by the Bayer chemist Felix Hoffmann over 100 years ago. The prevailing view in the biochemical community has been that aspirin works primarily, if not exclusively, by irreversibly inhibiting the enzymatic activities of cyclooxygenases 1 and 2 (COX1 and COX2), thereby disrupting the synthesis of inflammation-inducing prostaglandins. However, this assumption ignores two important facts.

First, aspirin is rapidly converted to salicylic acid (SA) in the body. Indeed, almost all aspirin is metabolized to SA within an hour after ingestion.

Second, SA and many of its natural plant derivatives are rather poor inhibitors of COX1 and COX2 as compared to aspirin, yet SA and aspirin have nearly the same beneficial pharmacological effects. Thus, there must be additional targets through which aspirin/SA exerts its many effects. Over the past two decades, a number of proteins whose activities are altered by aspirin/SA have been identified; however, their relevance as aspirin/SA targets has been called into question due to the very high, non-physiological levels of aspirin/SA required to alter their activities.

In light of our unexpected discovery that SA mediates its physiological effects in plants via many targets, and given that SA is a key hormone produced by all plants, we hypothesized that there might be multiple targets through which SA acts in animals, regardless of whether it is obtained in low to moderate levels via the diet or in moderate to high doses through herbal-based medicines or aspirin usage. 

Medical Research: What are the main findings?

Prof. Klessig: To investigate whether aspirin/SA exerts its pharmacological activities by targeting proteins besides the cyclooxygenases in humans, we used high-throughput approaches developed to identify proteins that mediate SA signaling in plant immunity. This strategy identified several proteins that bind SA and as a result they exhibit altered activity, including High Mobility Group Box1 (HMGB1). In the body, HMGB1 is normally found inside the cell’s nucleus where it helps package the DNA so that it fits in the nucleus. However, HMGB1 also can be released outside of cells following tissue injury or secretion by certain immune or cancer cells. Once in this extracellular location, HMGB1 triggers inflammation by recruiting immune cells involved in fighting infection and repairing damaged tissue. HMGB1 also stimulates these recruited immune cells to express genes that code for pro-inflammatory signaling proteins called cytokines. These pro-inflammatory activities of HMGB1 are associated with many prevalent and devastating diseases, including rheumatoid arthritis, lupus, heart disease, sepsis, and colorectal and mesothelioma cancers.

In collaboration with Marco Bianchi’s group at San Raffaele University and Research Institute in Milan, Italy and Gaetano Montelione’s group at Rutgers University in New Jersey, we have discovered that SA binds to HMGB1, thereby blocking its pro-inflammatory activities. It does so at concentrations that are far lower than those required to suppress the enzymatic activity of COX1 and COX2. Notably, we have discovered that HMGB1 also induces the expression of the gene encoding COX2, and that low levels of SA suppress this induction. Thus, SA does act, in part, through its effect on cyclooxygenase, but it does so by inhibiting the production rather than the activity of this enzyme. The discovery that HMGB1’s various pro-inflammatory activities are inhibited by low levels of SA provides at least one likely explanation for the protective effects of low-dose aspirin usage.

Importantly, we also have identified several natural and synthetic derivatives of SA that bind to HMGB1 more tightly than aspirin/SA and inhibit its pro-inflammatory activities much more effectively (40 -1000 fold). Interestingly, these natural derivatives are produced by an herb used in traditional Chinese medicine, while the synthetic derivative was designed based on both the structure of the herbal derivative and our studies of the binding activities of other SA-like compounds with HMGB1 and other SA-binding proteins from plants and humans.

     In conclusion, the identification of HMGB1 as a novel pharmacological target of SA/aspirin provides new insights into the mechanisms of action through which this widely used drug reduces inflammation and inflammation-associated diseases. Moreover, the existence of natural and synthetic SA derivatives that are even more potent than aspirin/SA at suppressing HMGB1’s pro-inflammatory activities argues that there is tremendous potential for developing SA-based drugs that retain all of the beneficial properties of SA but lack its deleterious side effects.

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Aspirin Prolongs Survival In All GI Cancers Except Pancreatic

M.A. Frouws, Study Coordinator ASPIRIN trial MD PhD Candidate Datacenter Heelkunde, K6-R Leiden University Medical Center Leiden, the NetherlandsMedicalResearch.com Interview with:
M.A. Frouws, Study Coordinator ASPIRIN trial
MD PhD Candidate
Datacenter Heelkunde, K6-R
Leiden University Medical Center
Leiden, the Netherlands

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

Response: The effect of aspirin on cancer survival has been the topic of many studies for a few decades. Epidemiological evidence shows a dual role in the relation between aspirin and cancer; both preventative and therapeutic effects are suggested. The biological mechanism of the effect of aspirin on cancer is still part of debate. However research up until now was mainly done at a single tumor location, mostly colorectal cancer. Since little is known about the etiology of the effect of aspirin, we have undertaken in this study. The aim of this study was to investigate the effect of the use of aspirin after diagnosis on survival in patients with cancer from the gastrointestinal tract. Stratification in specific localizations in the entire gastro intestinal tract could lead to new insights towards the effect of aspirin as a therapeutic agent.

We studied 13.715 patients and found a really significant survival benefit in patients taking aspirin after diagnosis of gastrointestinal malignancies, except for pancreatic cancer. Survival in patients with gastro intestinal malignancies taking aspirin after diagnosis showed to be twice as high as patients not taking aspirin. At five years after diagnosis, 75% of patients were alive who took aspirin, versus 42% of the patient group not taking aspirin. This effect persisted after correcting for several confounding factors, including age, disease stage and comorbidity.

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Only Regular Use of Low Dose Aspirin Offers Colon Cancer Protection

Søren Friis, Senior Scientist, Associate Professor, MD Danish Cancer Society Research Center Danish Cancer Society Department of Public Health University of Copenhagen Faculty of Health Institute of Clinical Medicine Department of Clinical Epidemiology Aarhus University DenmarkMedicalResearch.com Interview with:
Søren Friis, Senior Scientist, Associate Professor, MD
Danish Cancer Society Research Center
Danish Cancer Society
Department of Public Health
University of Copenhagen
Faculty of Health Institute of Clinical Medicine
Department of Clinical Epidemiology
Aarhus University Denmark


Medical Research: What is the background for this study?

Dr. Friis: Although laboratory, clinical, and epidemiological studies have all provided strong evidence for protection against colorectal cancer from regular use of aspirin, the optimal dose and duration of use for cancer prevention remain to be established.

Medical Research: What are the main findings?

Dr. Friis: Continuous use of low-dose aspirin for five or more years was associated with a reduced risk of colorectal cancer, but overall long-term use (continuous or non-continuous) was not. Long-term, high-intensity use (average of ≥0.3 daily doses) of non-aspirin NSAIDs was associated with a substantially reduced risk of colorectal cancer, particularly for NSAIDs with the highest COX-2 selectivity.

The results for long-term continuous users of low-dose aspirin should be interpreted cautiously, since these patients comprised only a small proportion of the low-dose aspirin users and might have a risk profile different from that of the general population.

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Almost A Third of Adults With Heart Disease or Stroke Don’t Take Aspirin Regularly

Dr. Jing Fang Ph.D. Epidemiologist Center For Disease ControlMedicalResearch.com Interview with:
Dr. Jing Fang Ph.D.
Epidemiologist
Center For Disease Control

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

Dr. Fang: Although the effectiveness of aspirin for secondary prevention (e.g. people who already have coronary heart disease or have had an ischemic stroke) of cardiovascular disease has been determined, its prevalence as a preventive measure has varied widely across settings, data collection methods and U.S. states. As a result, we wanted to more closely examine aspirin use among U.S. adults with a history of coronary heart disease or stroke.

To determine these findings, we analyzed data from the 2013 Behavioral Risk Factor Surveillance System. Nearly 18,000 people from 20 states and the District of Columbia with a self-reported history of coronary heart disease or stroke were included in the annual telephone survey.

Overall, we found about 70 percent of U.S. adults with heart disease or stroke reported regularly taking aspirin – meaning every day or every other day. Out of that group, nearly 94 percent said they take aspirin for heart attack prevention, about 80 percent linked it to stroke prevention efforts, and approximately 76 percent said they use it for both heart attack and stroke prevention. However, four percent of respondents with pre-existing cardiovascular problems said they take aspirin for pain relief without awareness of its benefits for cardiovascular disease.

Aspirin use also differed by state and sociodemographic characteristics including gender, race/ethnicity and age. In general, men, non-Hispanic whites, individuals aged 65 and older, and people with at least two of four risk factors (hypertension, smoking, diabetes and high cholesterol) are more likely to use aspirin than other groups. By state, aspirin use ranged from 44 percent in Missouri to more than 71 percent in Mississippi.

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Aspirin Inhibits Growth of Mesothelioma Cells in Mouse Model

Dr-Haining-Yang
MedicalResearch.com Interview with:
Haining Yang MD Ph.D
Associate Professor
Thoracic Oncology Program
University of Hawaii Cancer Center
University of Hawaii, Honolulu, HI

Medical Research: What is the background for this study?

Dr. Yang: Mesothelioma is often caused by asbestos and other carcinogenic mineral fibers.  When these fibers lodge in the pleura, mesothelial cells and macrophages try to phagocytize and eliminate them. However, asbestos is very bio-persistent and cannot be eliminated, which caused cells undergoing programmed necrosis that leads to the release of HMGB1 into the extracellular space.  HMGB1 is a damage-associated molecular pattern molecule (DAMP) that causes inflammation. Asbestos exposure induces HMGB1 release and chronic inflammatory process that overtime may lead to malignancy.  Mesothelioma cells develop out of an environment that is rich in HMGB1 and are often dependent on HMGB1 for their own growth.  In fact, most mesothelioma cells actively secrete HMGB1 extra-cellularly to promote their own tumor growth.  Accordingly HMGB1 levels are high in the serum of mesothelioma patients (reviewed in Yang and Carbone, Clinical Cancer Res 2013).  We tested several anti-inflammatory agents to see if we were able to reduce HMGB1-induced mesothelioma cell growth, and none of them worked except for aspirin, that led us to conduct a series of experiments in vitro and in vivo to test the hypothesis that aspirin inhibits HMGB1 activities, and that by doing so, inhibits mesothelioma growth.

Medical Research: What are the main findings?

Dr. Yang:  We found that aspirin inhibits the growth of human mesothelioma cells in a xenograft model, moreover in vitro experiments demonstrated that this effects was specifically mediated via inhibition of HMGB1 and not via COX2 inhibition.  We propose that the so far enigmatic anticancer activity of aspirin is mediated, at least partially, via inhibition of HMGB1, and that aspirin may help delay the onset of mesothelioma and may help inhibit the growth of mesothelioma.

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Aspirin Response Predicts Outcome After Stent Surgery

MedicalResearch.com Interview with:
Katharina Mayer MD
Deutsches Herzzentrum München,
Technische Universität München,
Munich, Germany

Medical Research: What are the main findings of the study?

Dr. Mayer: Patients whose platelets do not respond well to aspirin carry a higher risk of death or stent thrombosis. Platelet response to aspirin is an independent predictor of ischemic events in patients undergoing percutaneous coronary interventions (PCI).
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Does Aspirin Reduce Cancer Incidence and Mortality ?

Dr. Mangesh Thorat MBBS, MS(Surgery), DNB(Surgery), MNAMS Centre for Cancer Prevention Wolfson Institute of Preventive Medicine Barts & The London School of Medicine and Dentistry, London EC1M 6BQ Queen Mary University of Londonm Honorary Clinical Lecturer Division of Surgery and Interventional Science Whittington Hospital, LondonMedicalResearch.com Interview with:
Dr. Mangesh Thorat
MBBS, MS(Surgery), DNB(Surgery), MNAMS
Centre for Cancer Prevention
Wolfson Institute of Preventive Medicine
Barts & The London School of Medicine and Dentistry, London
Queen Mary University of Londonm Honorary Clinical Lecturer
Division of Surgery and Interventional Science Whittington Hospital, London

Medical Research: What are the main findings of the study?

Dr. Thorat : Accumulating evidence supports an effect of aspirin in reducing cancer incidence and mortality. Our analyses show that for average-risk individuals aged 50-65y taking aspirin for 10 years, there would be a relative reduction of between 7% (women) and 9% (men) in the number of cancer, myocardial infarction or stroke events over a 15 year period and an overall 4% relative reduction in all deaths over a 20 year period. The benefits of aspirin use would be most visible in the reduction in deaths due to cancer. If the findings of our study are applied to the UK general population aged 50-64 taking aspirin for next 10 years, on an average more than 6000 lives will be saved every year.
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