Estimated reading time: 8 minutes
I often encounter people who have taken baby aspirin for years because somebody once told them it was a good idea.
In fact, low-dose aspirin is quite popular among healthy people for the purpose of reducing the risk of heart disease and stroke. Tens of millions of people in the United States take it daily to reduce their risk of heart attack or stroke. And, numerous studies over the last two decades have suggested that taking aspirin on a regular basis may substantially the risk of developing or dying from cancer. (1).
But, does everybody benefit from aspirin? Probably not. Then, who should take it and who should not?
Aspirin is not without side effects. Therefore, it is important to weigh the benefits against the risk of adverse effects.
The history of the drug may be traced back to ancient civilizations when patients were advised to chew on the bark of the willow tree to cure fever and relieve pain and inflammation.
In 1828, Joseph Buchner, professor of pharmacy at Munich University, Germany managed to extract a substance he called salicin from willow. Salicin has powerful pain-relieving and anti-inflammatory effects.
The active ingredient in Aspirin, acetylsalicylic acid, was synthesized for the first time in 1897 by a young chemist working for Bayer, Dr. Felix Hoffman (2).
In 1899, acetylsalicylic acid was named Aspirin by Bayer. The letter ‘A’ stands for acetyl, “spir” is derived from the plant known as Spiraea ulmaria (meadowsweet), which yields salicin, and “in” was a common suffix used for drugs at the time of the first stable synthesis of acetylsalicylic acid (3).
Thus, aspirin is one of the oldest and most commonly used drugs to relieve pain and cure fever.
The first randomized study suggesting that a single daily dose of aspirin might reduce the risk of death among people with coronary heart disease was published in 1974 (4). Since then, many trials have studied the usefulness of the drug for disease prevention.
Today, low-dose aspirin plays a key role in the treatment of cardiovascular disease (CVD), a common cause of death and disability worldwide. CVD includes coronary heart disease, cerebrovascular disease (vascular disease of the brain) and peripheral artery disease (arterial disease of the limbs).
Low-dose aspirin is defined as 75-100 mg daily. A baby aspirin in the U.S. contains 81 mg of acetylsalicylic acid. This is much lower than the doses needed to relieve pain or reduce inflammation.
How Does Low-Dose Aspirin Work?
Platelets (thrombocytes) are small blood cells that are important in the formation of blood clots. One of their key functions is to stop bleeding. Aspirin interferes with the ability of platelets to aggregate or clump, thereby reducing clot formation.
Platelets participate in the development and progression of atherosclerosis (5), the main underlying cause of cardiovascular disease. Furthermore, they are key components of blood clots that form on atherosclerotic plaques (thrombosis) and often severely limit blood flow to important organs such as the heart and the brain. Thrombosis is a term for blood clot occurring inside a blood vessel.
Thromboxane A2 is a substance that plays a key role for the clumping of platelets and their blood clotting activity.
The best-characterized mechanism behind the effects of low-dose aspirin is its inactivation of an important platelet protein called cyclooxygenase-1 or (COX-1)(6).
The inactivation of COX-1 leads to a long-lasting suppression of thromboxane A2, thereby suppressing platelet activation and aggregation (7).
Higher doses of the drug also inhibit COX-2, which blocks prostaglandin production leading to the drugs’ effect on pain, inflammation, and fever.
The effects of the drug on platelet function explains its effectiveness in preventing thrombosis as well as its bleeding liability.
tyle=”color: #993300;”>Aspirin for Patients with Cardiovascular Disease (Secondary Prevention)
Among patients with established CVD, such as history of stroke or heart attack, both individual studies and meta-analyses of randomized trials indicate that low-dose aspirin reduces the risk of a new cardiovascular event (heart attack, stroke or death from vascular causes) by approximately 25 percent (8).
The positive effect of the drug in secondary prevention is to a certain extent offset by an increased risk of bleedings from the gastrointestinal tract and an increased risk of brain hemorrhage. However, the risk/benefit ratio is clearly in favor of aspirin treatment.
Consequently, all patients with established CVD should be offered daily treatment unless there is an excessive risk of bleeding.
Aspirin for Healthy People (Primary Prevention)
It has been suggested that aspirin may reduce the risk of CVD and some types of cancer among healthy people.
Aspirin in Primary Prevention of Cardiovascular Disease
Among people without a history of CVD (primary prevention), the risk reduction associated with treatment is much smaller than among those with a history of a vascular event.
Several large meta-analyses have addressed the effects the drug for primary prevention (9,10). Taken together the results of these trials suggest that such treatment leads to a 20 percent relative reduction in the risk of heart attack (myocardial infarction), no significant effect on the risk of stroke, no significant effect on the risk of death from cardiovascular disease, and a 54 percent relative increase in the relative risk of bleedings, mostly from the gastrointestinal tract.
There are several ongoing trials addressing the question whether people at increased risk, such as those with diabetes, may benefit from low-dose aspirin.
Based on the currently available date, the risk/benefit profile of low-dose aspirin does not support such treatment for people without a history of CVD. The ratio of benefit to risk is much lower than in people with established CVD. Therefore, inappropriate over-prescription of the drug for primary prevention should be avoided.
For some individuals age 50 years or greater without underlying CVD and without excess bleeding risks, the benefits of treatment for the prevention of cancer and CVD may outweigh the risks (11). The evidence does not support the routine use of the drug for primary prevention in patients younger than 50 years.
Aspirin for Prevention of Cancer
There is evidence that low-dose aspirin used over prolonged periods may reduce the risk of several types of cancer (12). The strongest evidence for this effect relates to of cancer of the colon and rectum (13).
Randomized studies on the effect of the drug on the primary and secondary prevention of CVD have indicated that long-term treatment is associated with a reduction in cancer-related mortality. This may be explained by an effect on cancer prevention as well as a decrease in the spreading of cancers (metastasis)(14).
Aspirin and Mortality
As low-dose aspirin appears to reduce the risk of coronary heart disease and some cancers at the same time as it increases the risk of bleeding, it might be prudent to ask if aspirin treatment prolongs life.
The effect on total mortality has been addressed in at least three meta-analyses (8,15,16). All these studies suggest that low-dose aspirin leads to a 6-8 percent relative reduction in total mortality. However, this effect is not clearly statistically significant suggesting that we can not be completely sure that there is an effect on all-cause mortlity.
Adverse Effects of Aspirin
The most common side effect of treatment is bleeding, most commonly from the gastrointestinal tract. Bleedings may also occur at other sites, with intracranial bleeding (brain hemorrhage) being the most serious.
Several factors that may increase the risk of gastrointestinal bleeding associated with regular intake of the drug have been defined (17). These are: a history of peptic ulcer disease or gastrointestinal bleeding, older age, concomitant use of non-steroidal anti-inflammatory drugs (NSAID’s), concomitant use of other blood-thinning drugs, the presence of other underlying disease (e.g. diabetes, hypertension), and high aspirin dose.
Sometimes, so-called proton pump inhibitors (PPI) are used to prevent drug-induced gastrointestinal bleeding. PPI’s are drugs used for the treatment of peptic ulcer disease. However, such treatment is not considered cost-effective for people with a low or average bleeding risk (18) which includes most people using aspirin for the purpose of primary prevention.
Some people do not tolerate the drug because of hypersensitivity, usually manifested as respiratory symptoms such as rhinitis (inflammation of the mucous membranes of the inside of the nose) and asthma. More severe symptoms have been described but are rare.
The Take Home Message
Long-term treatment with low-dose aspirin appears to reduce the risk of cardiovascular events and some types of cancer.
Evidence suggests that patients with an established cardiovascular disease, such as a history of heart attack or stroke, benefit from low-dose aspirin.
In patients without a history of cardiovascular disease, the benefit/risk profile does not support routine treatment with low-dose aspirin. In this group of people, inappropriate over-prescription should be avoided.
For some individuals age 50 years or greater without underlying cardiovascular disease and without excess bleeding risks, benefits of low-dose aspirin may outweigh the risks.
Bleeding, most commonly from the gastrointestinal tract, is the most common adverse effect of treatment.
Studies are under way to address the question whether specific subgroups, such as people with diabetes or elderly people, will benefit from low-dose aspirin.
As usual you have a gift of exposing complex and conflictual evidence in a very clear way. Thanks
Thanks Robert.
Appreciate your interest and your kind words.
Why not recommend fish oil to equal about 2000mg of EPA for similar effect without the side-effects?
Fred
That’s a good point. Fish oil might be an alternative to aspirin although there’s no study that has directly compared these two.
In fact I’ve recently written a summary on the health effects of fish oil https://www.docsopinion.com/2014/10/16/benefits-of-fish-oil-and-marine-derived-omega-3-fatty-acids/
Interesting and related recent post by
2 lovely people and scientists….Fred and Alice Ottoboni.
Keep in mind, They are both in their
mid 90’s and highly qualified and experienced.
https://ketopia.com/lowly-aspirin-versus-nsaid-challengers/#comments
Also of interest is this: https://ketopia.com/aspirin-a-unique-remedy/#more-1425
Dr. Sigurdsson,
I am curious. How do you define real CVD?
For example, I am 65 and have some arterial calcification, per a heart CT scan. But I do not have any measurable symptoms that indicate CVD, per my doctor and Vap+ blood tests.
Using your expert definition (i.e. understanding), would my calcification qualify as CVD? If yes, should minor calcification conditions dictate a low-dose aspirin approach.
Would your answer be different if same person has a low fibrinogen levels, low Lp-PLA2 measurements and low inflammation markers?
Thanks.
PJ Cart
PC Cart
That is a very important and relevant question. Strictly speaking, secondary prevention deals with people with a history of cardiovascular event such as a heart attack or stroke. However, it also covers more stable conditions such as chronic ischemic heart disease and peripheral artery disease.
So, probably, slight coronary calcification would not be defined as secondary prevention, meaning that using aspirin may be debated. Unless there are other factors, such calcification would probably not be reason enough to advise low-dose aspirin. However, the decision may depend on the amount of calcium https://www.docsopinion.com/2014/08/19/coronary-calcium-score/
There is probably an intermediate, grey area where aspirin might be recommended in primary prevention, such as individuals above age 50 considered high risk because of factors such as family history of premature cardiovascular disease, hypertension, lipid abnormalities etc.
Low fibrinogen levels, low Lp-PLA2 measurements and low inflammation markers would certainly not support aspirin treatment in a 65 year old.
Thanks much for your opinion. Based on a lot of research and reading, I came to the same conclusion regarding the aspirin solution. Although my doctor and cardiologist wanted me on both aspirin and statins, they were forced to admit that all my other markers (after numerous blood draws and tests) no longer indicated a need.
Yet, the GP keeps insisting that I have ‘CVD’ needing medications. I keep reminding him my current health indicators are good and that that 35+ years of smoking and no exercise did some obvious damage, plus being Apoe 3/4 probably did not help.
Btw, I went counter to their nutrition/diet recommendations after avoiding fat and cholesterol for many years. After doing my own research, I ditched their conventional low-fat approach and went to a high-fat percentage diet (and a regular, but moderate exercise program).
That’s when all my bio-markers improved (exceptions being TC and LDL) dramatically, much to their chagrin. Note: my LDL did change from the small dense type to the larger, fluffier variety. I should add that I did not see much bio-marker improvement for the first 3-6 months (in fact, some got worse, in a very scary way) but at a certain point the big improvements across-the-board developed and have remained. And I am now back down to my former skinny college-age self, running 5k’s.
Thus, I am going to save the helpful low-dose aspirin approach until my later years to whenever bodily indicators finally suggest it would have real value to my health.
Again, thanks for your expert insight, opinions and articles.
So all the biomarkers EXCEPT the often–oh-so-very-essential one improved, huh?
You’re of course entitled to your choices. But I’d think it’d make more sense to improve them all …
Mie.
Nobody’s perfect. I think this is a good example of someone who’s trying to improve his/her health in a very responsible manner. I wouldn’t worry about TC and LDL-C lagging behind.
And you wouldn’t worry because …? Usually, dramatic weight loss (he mentioned being back to his former, skinny self) is more than enough to improve lipid levels all around, but evidently not so in this case. So what do you think happens when the weight loss slows down and/or weight gain begins?
Of course, it’s responsible to try to improve one’s health. However, just being “responsible” may not be enough if you’re not changing ALL and/or KEY risk factors.
What was the change in your TG/HDL Ratio?
Dear Dr. Sigurdsson,
I have been reading about your interesting website. You are a great doctor and I would like to seek your expertise for the 2 questions below. Your help would be tremendously appreciated.
I am a 68 years old skinny Chinese woman with plaques in my coronary arteries and dyslipidemia:
1). Calcium Score = 96
Less than 30% stenosis in LAD, No stenosis in RCA & CIRCUMFLEX, No carotid plaque.
2). Dyslipidemia: LDL = 5.2 mmol/L; HDL = 1.9 mmol/L; Total Cholesterol = 7.5 mmol/L; Triglyceride = 0.6 mmol/L
Apo-B= 1.22 g/L
Apo-A1= 1.86 g/L
Apo-B / Apo-A1 ratio= 0.66
Sometimes I have irregular heart beats, but only very occasionally like once in a month.
I don’t have other risk factors. I never have a heart attack nor stroke, normal blood pressure, not diabetic, no family history of heart disease and non smoker.
I have low inflammatory markers with hs-CRP < 0.4 mg/L; Lp PLA2 = 205 nmol/min/ml (< 225 represents reduced risk in the report)
1). I am not taking any medications. With a Calcium Score of 96 and a LDL of 5.2 mmol/L at the age of 68 years old, Will you recommend me to take Aspirin?
2). With a LDL of 5.2 mmol/L, Do you think I have the genetic disorder called familial hypercholesterolemia?
Thank you very much for your expertise and tremendously appreciated for your care. I look forward to hear from you.
Best,
Claire