Scientific Reports, Media Reports and Ambiguity

Last week I read an article in a peer reviewed journal citing the benefits of a few eggs per week as part of a low carbohydrate dietary intervention for Type II Diabetes.  The information was so meaningful about a controversial food source of protein that I decided to write about it in my blog and pass it along to my patients.  Three days later the American Heart Association and American College of Cardiology discussed the increased risk of cardiovascular events and mortality in individuals consuming three or more eggs regularly. They talked about the detrimental cholesterol being concentrated in the yolk making egg white omelets look healthier than traditional omelets.

In the early 1970’s a VA study was published showing that veterans over 45 years of age who took an aspirin a day had fewer heart attacks and strokes and survived them better than those who don’t.  Fast forward almost 50 years and we have different recommendations for people who have never had an MI or CVA or evidence of cardiovascular disease compared to secondary prevention in individuals who have known coronary artery disease, cerebrovascular disease or diabetes. Throw in the controversial discussions of aspirin preventing colorectal adenomas from developing, aspirin preventing certain types of skin cancers and today’s report that suggests it may prevent liver cancer. Now three studies suggest that in older individuals (70 or greater) the risk of bleeding negates the benefits of cardio and cerebrovascular protection and aspirin may not actually prevent heart attacks and strokes in that age group.

We then turn to statins and prevention of heart attacks and numerous articles about not prescribing them to older Americans.  I saw articles on this topic covered by CNN, the Wall Street Journal, ARP Journal, AAA magazine and in several newsletters published by major national medical centers.  In each piece they caution you to talk to your doctor before stopping that medicine.

I am that seventy year old patient they all talk about.  I have never smoked. I exercise modestly on a regular basis, getting my 10,000 or more steps five or more days a week.  I battle to keep my weight down and find it difficult to give up sweets and bread when so many other of life’s pleasures are no longer available due to age and health related suggestions.

There are clearly no studies that look at patients who took a statin for 15 years and aspirins for over 20 years, stopped them and then were followed for the remainder of their lives.   How will they fare compared to patients who never took them?

I have this discussion every day with my patient’s pointing out the current guidelines and trying to individualize the suggestions to their unique lifestyle and issues. On a personal level, I still have no idea what the correct thing is to do even after discussing it with my doctors.  How can I expect my patients to feel any differently?

Aspirin for Breast Cancer?

Aspirin (2)In an observational study published in the Journal of Clinical Oncology in 2010, Drs. Michelle Holmes and Wendy Chen of the Harvard Medical School showed that women with breast cancer who took one aspirin per week had a 50% lower chance of dying from breast cancer. They have been trying to set up a randomized blinded study of 3000 women with breast cancer to test this finding using the gold standard of research but they have been unable to raise the $10,000,000 required for a five year study. Pharmaceutical companies see no profit in aspirin and prefer to use their research money on medications that are potentially more profitable. Government agencies seem to feel the same way opting to test new cancer drugs pushed by pharmaceutical companies rather than finance an inexpensive available product.

The authors believe aspirin, if proven to be effective in randomized trials, is a less expensive alternative for women who cannot afford or cannot tolerate hormonal therapy post-surgery for five years. Great Britain, through its national health service has decided to study the effects of aspirin on four cancers, with breast cancer one of them, in a study that will not be completed until 2025. Drs. Holmes and Chen believe that with proper funding their study of women with stage 2 and 3 breast cancer, would answer the question of aspirin’s efficacy within five years.

Low Dose Aspirin Cuts Colon Cancer Risk in Women

AspirinNancy Cook, SCD of Brigham and Women’s Hospital in Boston and colleagues reported in the July 16, 2013 issue of the Annals of Internal Medicine that data from the Women’s Health Initiative including 39,876 women 45 years or older, who were randomly assigned to take 100 mg of aspirin every other day for ten years, experienced a 20% reduction in the risk of colorectal cancer. The study did not show that there was an all-cause reduction in mortality .

The very conservative US Preventive Services Task Force currently recommends aspirin in Women 55 – 79 only if potential benefits are greater than harms. The aspirin group did have more bleeding from peptic ulcers and gastrointestinal bleeding. The article was accompanied by an editorial comment by Peter Rothwell, MD, PhD of the University of Oxford. He felt that the risk of bleeding and the fact that there was no all-cause mortality reduction, or risk in all cause cancer reduction, should result in a tempering of suggestions for widespread use of aspirin in healthy middle-aged women. MedPage Today, the online Journal of the University Of Pennsylvania School Of Medicine, ran a comment from Dr. Randal Burt, MD, a gastroenterologist at the Huntsman Cancer Institute who felt that this was one more piece of evidence that aspirin can reduce colorectal cancer.

It is clear that there are multiple studies showing that aspirin can reduce the risk of colorectal cancer. There are studies showing it reduces the risk of a stroke in women as well.

Like all decisions to take or prescribe a medication, the risks and benefits must be examined first. It is clear to me that in a woman with a strong family history of colorectal cancer, and little or no history of gastrointestinal or systemic bleeding, an aspirin with close monitoring should seriously be considered.

Is Aspirin Resistance A True Entity?

Aspirin

Aspirin has been a recognized agent to inhibit platelet function and prevent clotting.  We use it to prevent heart attacks and strokes. It’s used in individuals who have a transient ischemic attack or mini-stroke to prevent a future major stroke. It’s also used as a component of the therapy in patients who have stents put in arteries to relieve arterial blockages.

Despite the use of the aspirin, either alone or in concert with other medications, a certain percentage of patients do have the heart attack or stroke we are hoping to avoid. Scientists have postulated that a number of these patients have a condition called aspirin resistance. They believe aspirin may not work in them due to genetic factors that affect the way aspirin works. The belief is so strong that certain labs now offer genetic assays to assess whether you are a patient with aspirin resistance.

Garret A. FitzGerald, MD, and associates from the University of Pennsylvania published their research in the online section of Circulation: Journal of the American Heart Association which questions the existence of aspirin resistance at all. They recruited 400 healthy non-smoking participants between the ages of 18- 55 to measure the response to the ingestion of a traditional 325 mg regular aspirin or an enteric coated version.  They were able to use several different well accepted measures of aspirins anti-platelet effects to divide the group into aspirin responders and non-responders. They basically found that the non-responders were primarily individuals who received enteric coated aspirin. When you tested their blood in the laboratory with regular non-coated aspirin, or tested them with non-coated aspirin, they suddenly became responders.  FitzGerald and colleagues concluded that “pseudo resistance is caused by delayed and reduced absorption of coated aspirins.”

Doctors and pharmacists have encouraged the use of “coated” aspirin to offset aspirin’s tendency to irritate the lining of the stomach and duodenum and initiate gastrointestinal bleeding. Based on this paper it seems reasonable to suggest to patients that they use regular uncoated aspirin to achieve the desired anti-platelet effect if the patient is not high risk for intestinal bleeding.

 

Aspirin – Cardiovascular and Cancer Benefits

In this week’s on line edition of MedPage, a publication of the University Of Pennsylvania Perelman School Of Medicine, they summarize a series of articles published in the prestigious medical journal Lancet, which conclude that taking aspirin daily reduces your risk of cancer.

Aspirin received its notoriety after a Veterans’ Administration study years ago noted that if you took a daily aspirin and were a male over 45 years old you had fewer heart attacks and strokes. That classic study has led to the recommendation over the years that everyone over the age of 45 years old take aspirin daily to prevent cardiovascular events. No one can quite agree on the dosage of a full aspirin (325 mg), a baby aspirin (81 mg), or two baby aspirin?

As more and more people began taking aspirin for cardiovascular benefits researchers noted more frequent episodes of major internal bleeding either in the gastrointestinal tract or in the brain and head. At the same time, it was whispered among professionals that taking aspirin daily reduced adenomatous growths in the colon (pre-malignant polyps) and reduced colon cancer.   In the past few weeks several studies have tried to stratify whether aspirin use daily should be restricted to men as opposed to women, or to individuals with documented heart and vascular disease for secondary prevention of the next heart attack or stroke rather than primary prevention.  They cited the large number of bleeding episodes in individuals trying to protect themselves from their first heart attack or stroke compared to the events prevented and lives saved.

Today’s MedPage review of three Lancet articles claims that daily aspirin use reduces the risk of adenomatous cancer by 38% and cancer mortality by 15%. It reduces the development of metastatic disease by up to 15%.  These studies looked at more than 51 trials, including well over 100,000 participants, leading Dr Peter Rotwell of Oxford University in the United Kingdom to say that the papers “add to the case for the long term use of aspirin for cancer prevention in middle age.”

As a primary care physician I will continue to take my daily 81 mg enteric coated buffered aspirin (2) with food and take my chances with GI bleeding and cerebral hemorrhage.  If my patients do not have any strong contraindications to aspirin ingestion I will continue to make the suggestion that if they are over 45 years old they consider doing the same.

Aspirin Use for Prevention of Cardiovascular Disease

A study by the Veterans Administration in the 1970’s on veterans over age 45 showed that if they were given aspirin they had fewer heart attacks and strokes.  This study didn’t divide the participants into men and women or patients who never had a heart attack or stroke versus patients who had known cardiac, Cerebrovascular and or Vascular Disease already.  The exact dosage of aspirin to take was never quite clarified either. For years physicians prescribed “baby aspirin” to patients over 45 to prevent heart attacks and strokes. While no definitive evidence existed to show the benefit was present in women as well as men, we tended to recommend the low dose aspirin in that group as well unless they were a high risk for bleeding.

Recent studies have questioned whether daily aspirin use for primary prevention of vascular disease is beneficial.  The current opinion is that a daily aspirin may cause more harm than good in women.  There is a feeling that the risk of bleeding may outweigh any benefit. The data is not quite as clear in men.  To add to the confusion, an article published in the journal Ophthalmology asserts that in a European study aspirin use was associated with an increased risk of developing wet, age related macular degeneration (AMD). Of the 4691 participants in the study, 36.4 % developed early AMD and 17% of that group took aspirin on a daily basis.  This is not the first study to raise this question with equivocal findings on several previous studies concerning the relationship between aspirin intake and AMD.  It is clear that further research is needed in this area.

The study is one of many that raise conflicts in approaching AMD and eye disease versus systemic health. This is especially a problem since these older AMD patients are the same ones who are more likely to already have cardiac, Cerebrovascular or Peripheral Vascular Disease and this is the very group that we know and agree that aspirin is beneficial in.

Clearly more studies are needed. I will continue to take my daily 81 mg of enteric coated aspirins unless I develop aspirin related gastritis, ulcers or GI Bleeding. My male patients over 45 years old with low or few risks of GI bleeding will continue to be advised to consider aspirin. With no studies showing a clear cut advantage for women taking aspirin for primary prevention of heart disease and stroke, I will present the pros and cons of therapy and advise it less frequently if the patient has a low risk of vascular disease or a high risk of bleeding.

Aspirin Holiday Carries Its Risks

A recent publication in the British Medical Journal looked at the risk of stopping aspirin therapy and taking a drug holiday from it if you are taking aspirin as secondary prevention for heart disease. The study, conducted from 2000 – 2007, looked at almost 40,000 participants aged 50-84 who were taking low dose aspirin (75- 300 mg per day) for secondary prevention of cardiovascular outcomes. They followed the patients for 3.2 years.

Researchers determined that individuals who stopped aspirin for 1-6 months had significantly more myocardial infarctions (heart attacks) and cardiovascular deaths than individuals who continued the aspirin.  Most of the patients who stopped the medication just stopped it on their own for no particular reason.

The study has implications for patients who have known coronary artery disease, have had a heart attack or stent placed or have survived bypass surgery. It says that if you stop the aspirin you increase your risk of having a cardiac event.

As a physician I am always faced with phone calls from patients going for minor dental work and the dentist insists on stopping the aspirin. I have patients going for elective cosmetic procedures who are required to stop their aspirin.  The message must be “is the risk of excessive bleeding from the elective procedure greater than the risk of having a heart attack?”  This is a question you should ask your cardiologist, internist or family physician before stopping the aspirin. You and they will need to ask your dentist or surgeon the same question before you stop the aspirin.

There will be times when you will have no choice but to accept that increased risk to have work done which may be necessary.  By informing your physician of the problem, and discussing it with the surgeon or dentist, we can determine if stopping the aspirin is essential and if there are other measures we can take to prevent a cardiac event.