Benefits and risks of aspirin in the context of its anti-cancer potential

Aspirin has been reported to have the potential to prevent selected cancers of the digestive tract. Aspirin also reduces the risk of serious vascular diseases in patients already at higher risk of them. A team led by researchers from the University of London has published their assessment of the risks and benefits of aspirin by analysing previous reports of the effects of aspirin.

Aspirin is a powerful drug with powerful adverse effects, including bleeding into the digestive tract or brain, causing some forms of asthma, exacerbating gout and causing rare but serious complications in children under 16 years of age ...

See more on this in Spanish on the BBC World Service website.

Below is an English version of the BBC World Service report:

" Myth and reality of aspirin to prevent disease

Writing

BBC Mundo

Aspirin is one of the world's best selling drugs. More than two thousand years ago, Hippocrates, the Father of Medicine, discovered the active ingredient in aspirin, which he extracted from the willow plant, and used to soothe fevers and headaches.

But it was not until 1897 that the German Felix Hoffman developed the drug as such. More than a century later, aspirin, acetylsalicylic acid, is one of 10 generic best sellers in the world, with annual sales of about $ 1.7 billion.

Besides being a recognized analgesic, aspirin has gained ground as way to prevent certain diseases. Multiple studies have highlighted its benefits in preventing cardiovascular disease and various cancers.
However, taking aspirin regularly involves significant risks. BBC News spoke to several experts to discuss how and when it is advisable to take a dose of this medicine each day.

Cardiovascular Benefits

Taking a daily dose of aspirin is a method widely used to prevent cardiovascular disease in people who have had this disorder already.

Mike Knapton, associate medical director at the BHF, told the BBC that for people who have had heart attacks, angina, some types of stroke and diseases of the arteries, a low dose of aspirin a day can prevent the occurrence of new episodes. This practice is well established and several studies have demonstrated these benefits.

The reason is that aspirin inhibits platelet adhesion in blood vessels reducing blood clotting.  But research also points that the drug may not prevent cardiovascular events in healthy people.  Rather, "the risks of taking a daily dose of aspirin outweigh the benefits of taking it in the case of people who have never had this kind of disorders," said Dr. Mike Knapton.

Reduction of cancer

In recent years, several studies have also pointed to the benefits of the drug as a way to prevent certain types of cancer. Experts also point out that aspirin increases the risk of bleeding. In fact, Peter Elwood, a British expert who participated in the scientific team that first showed the benefits of this analgesic in cardiovascular disease states that "the future is aspirin in reducing certain types of cancer."

Recent research by Queen Mary University of London, argues that for people between 50 and 65 years, a dose of daily aspirin can significantly reduce the risk of developing colon, esophageal and stomach cancer.
"This study showed a 35% reduction in cases of colon cancer and 40% in the number of deaths from this disease," Julie Sharp, Director of the Health Information Department of the British charity Cancer Research UK told the BBC.

"In relation to stomach cancer and esophagus, a reduction of 30% in the number of cases and between 35% and 50% in deaths was recorded, "said the expert. The study recommends that people between 50 and 65 take a dose of 75 and 100 grams of aspirin for at least 5 years, preferably 10 years.

Significant risks

But some studies in the UK have indicated that in some cases, taking the drug may have more risks than benefits. One of the side effects of this drug is the possibility of internal bleeding, including brain. Experts agree that a daily dose of aspirin helps prevent cardiovascular problems in people who already suffer from these disorders.

As he explained to the BBC, Donald Singer, professor of clinical pharmacology in the department of medicine at Yale University in the United States, "as a result of its blood thinning effect, aspirin can cause bleeding, for example in people who have a stomach or intestinal ulcer, and in some cases it can also cause bleeding in the brain. "

Research from Queen Mary University of London recognizes these risks and stresses that in the case of persons 60 years of age who take a daily dose of aspirin for 10 years, the risk of bleeding in the digestive tract increased from 2.2% to 3.6%, and in a small proportion of these cases (5%), can lead to death. " It is important that in each patient assessment is done to establish who can take aspirin and who should not".

Julie Sharp, of the British charity Cancer Research UK said the risk increases significantly for people over 70 years.

But to what extent do the risks outweigh the benefits of aspirin?

Here is a point on which not all experts agree. "I have no doubt that the balance is in favor of taking aspirin for people over 50 years," Professor Peter Elwood told the BBC. He noted that, although the risk of bleeding is increased, there is no evidence aspirin is associated with fatal bleeding. "The evidence suggests that there is minor bleeding, but not fatal."

But a study from the University of London published in 2012 concluded that the medicine, taken daily, can do more harm than good to a healthy person.
Julie Sharp notes that precisely because it is not known with certainty who may suffer side effects, "it is important that in each case testing done to establish who should take aspirin and who is not."

Consult your doctor

The active ingredient of aspirin has been used to treat headaches for centuries. With so many studies highlighting the benefits of aspirin, thousands of people in several countries take the drug to prevent disease before presenting with any symptoms, something that according to Professor Donald Singer, a member of the British Pharmacology Society, can be very dangerous. "It's very important that people are aware of the risks and consult your physician" before taking long term aspirin treatment.

He explained that people who suffer from indigestion, or asthma, or who have gout or who are taking other drugs that inhibit blood clotting are at increased risks of the side effects of aspirin.

And that also applies to children under 16 years of age. "One might be tempted to give aspirin to a child, in the case of families with a history of colon cancer, such as prevention. But this is very dangerous because in the case of minors, a daily dose may cause liver damage."

It is also important not to take more than the dose of 75 mg, or a quarter of a standard dose of aspirin.

The benefits of aspirin to prevent disease in specific cases are well established, but experts insist that consulting a doctor is essential to reduce risks of adverse effects."

Progress on Personalized Medicine? Updates from Harvard.

@HealthMed The 8th annual Personalized Medicine Conference took place at Harvard this week - a joint venture of Harvard Medical School, Harvard Business School and Partners Healthcare, lead by Professor Raju Kucherlapati, from the HMS Department of Genetics. Worth checking the excellent archive of past programmes, presentations and podcasts.
Meantime, some of the highlights?
- An excellent narrative on the partnership between Plexxikon (Peter Hirth) and Roche Diagnostics (Suzanne Cheng) to create a companion diagnostic/therapeutic pairing for vemurafenib (Zelboraf), the first FDA approved pairing for BRAF V600E positive metastatic melanoma
- Further case studies illustrating successful drug development using genetic approaches
- Personal case studies on the impact, clinical value and ethical and clinical challenges of genomic screening: from Joe Beery, Life Technologies, on detecting unrecognised treatable serious early childhood disorders, to John Lauerman, Bloomberg News, on consequences of sequencing for asymptomatic adults - questions on penetrance and future screening for onset e.g.  of metabolic disease and cancers

Harvard Medical School: New Research Building - Avenue Pasteur.

- Clinical potential, and regulatory and reimbursement challenges to introducing molecular diagnostics into clinical care pathways
- Leadership award to Randy Scott, In Vitae, whose discussion points included the relevance of Moore's Law (technology advancing) and Metcalfe's Law (people factors: exponential increase in interaction as network expands) to developments in personalized medicine
- Business models and their governance for use of genetic information
- A North Virginia (John Vockley, Inova) pioneering series of projects aiming to assess outcomes of neonatal genomic sequencing: from insight into preterm labour to prospective longitudinal follow-up to adulthood, supported by multi-generation family member sequencing combined with clinical histories
- The US Air Force Programme on Patient-Centered Precision Care (Dr Cecili Sessions), in partnership with the Coriell Institute and Johns Hopkins University,  aims of which include understanding the impact on health-related behaviour of providing personal genetic information on remediable medical disorders and on drug responses.
- A business school case study led by Professor Richard Hamermesh, Director of the HBS HealthCare Initiative, on reactive and proactive responses for development of companion diagnostics (1).
- Pros and cons of liberal vs. restrictive approaches to IP for genetic and other molecular diagnostics
- Engaging the policy community and the public in ethical, clinical, reimbursement and adoption issues for new diagnostics and treatments aimed at personalizing medicine, including case studies from the American Medical Association and the American Assocation for Cancer Research.

Personalized Medicine Conference website 
Companion and coupled diagnostics

Networks and personalized medicine for better drugs?

For more on this theme see 
- article with Andrew Marsh in the inaugural March 2012 issue of Health Policy and Technology
- article in the October 2011 issue of Public Service Review: Science and Technology Review.  

For many individual patients treatments may not exist, may not be very effective, or may result in unpleasant adverse effects. How can prescribers improve drug selection andreduce the harmful effects of medicines? Are there better ways to develop drugs for patients who are difficult to treat?  And what can we do to improve poor adherence to medicines? These elements underpin ‘personalized medicine’, in current use the concept that by considering differences among patients in genetics, disease burden and other factors, more effective and safer drugs can be developed. Personalizing medicine is a path to better disease prevention and control where limited treatment options exist, such as for many cancers, resistant infections and dementia syndromes, and better drug development for new medical challenges. These concepts have in recent years attracted interest from the Royal Society, the Nuffield Council on Bioethics and cognate international institutions.

It is clear that there needs to be consistent investment and support from policy makers and regulators to develop and sustain the academic and industry pharmacology expertise and activity needed for the long-term success of a personalized medicine strategy, so that we can continue to be able to improve the health of the public and individual patients.

NICE is an international leader in developing evidence-based treatment guidelines. Its reports increasingly recognize the need to refine drug choice based on patient characteristics. For example, updated national hypertension guidelines released in August 2011 advise drug selection guided by age, gender, ethnicity, and monitoring, with treatment modified depending on clinical response. NICE also recognizes the need for research on ways, tailored to patient preference, to improve long-term adherence to drug treatment.

Pharmacologists are developing two complementary approaches aimed at achieving “precision medicine” in as many patients as possible: better drug discovery combined with high definition biomarkers for drug selection and monitoring. Network pharmacology brings together sophisticated databases of genetic mechanisms for disease, pharmacological pathways, candidate drugs, and population data describing important variants among individuals in drug handling and responsiveness.  These methods also allow ways to find previously unexpected “off-target” actions of existing or new drugs, which may accelerate discovery of new treatments for serious diseases.

Diagnostic methods are increasingly being used to improve drug selection for individual patients. For example growth tyrosine kinase receptors can be blocked using the biological agent imatinib to treat particular patterns of Philadelphia chromosome-positive chronic myeloid leukaemia, and rare gastro-intestinal tumours. Understanding genes and drugs that influence enzymes that modify drugs in the body, improves accuracy in defining patients who will not respond to a given medicine, or may develop adverse effects.  For example, to minimize risk of serious harm, pharmacogenetic testing is recommended for variability in a specific liver enzyme before deciding whether or not to prescribe the anti-HIV drug abacavir. This knowledge also allows better prediction of a patient’s risk of harm from interactions between treatments, based on recognition of medicines and other remedies that interfere with how drugs are cleared by the body. 

See my previous blogs on 
- preventing adverse drug reactions
- new UK guidelines on managing high blood pressure