Despite the remarkable advances in medicine over the past 20 years, cardiovascular disease and cancer will still kill half of us. Beyond the deaths, millions survive heart attacks, strokes and cancer, but many are left with disability and a reduced quality of life. While lifestyle changes can improve our odds of avoiding these diseases, they do not eliminate our risk. Finding ways to medically prevent these diseases before they occur, a term called “primary prevention”, is a holy grail in medicine. Primary prevention can be a tough sell, personally and medically. It means taking medicine (which may cause side effects) when you’re well, with the hope of preventing a disease before it occurs.
The US Preventative Services Task Force (USPSTF) released draft guidelines on the primary prevention of cardiovascular disease and colorectal cancer last week. The USPSTF is now recommending daily aspirin in some age groups who have at least a 10% risk of cardiovascular disease in the next 10 years. This isn’t the first guideline that’s recommended aspirin for primary prevention of cardiovascular disease, but it is the first major guideline to endorse aspirin to prevent colorectal cancer. Given these recommendations will apply to millions of people, they have attracted considerable controversy. Is this strategy going to reduce deaths and disability? Or are we about to start “medicalizing” healthy people inappropriately?
Why take Aspirin?
Aspirin or acetylsalicylic acid (ASA) has a long history of use with origins in a natural remedy, where willow bark was used as medicine as far back as 3000-1500 BCE. The active ingredient in willow is salicin which, after being isolated, was modified chemically in an attempt to improve the side effect profile. The ASA chemical structure was invented in 1899 by the pharmaceutical company Bayer, which still retains the right to the trademarked brand name “Aspirin” in some countries. ASA is generic, inexpensive, and one of the most widely used drugs in the world.
The analgesic and pain-relieving effects of ASA are well known. At high doses, ASA can be used to treat inflammatory diseases like rheumatoid arthritis. ASA appears to reduce the risk of heart attacks and strokes through mild anti-inflammatory effects as well as anti-platelet effects (reducing their “stickiness”). The effectiveness of ASA in preventing cardiovascular disease was demonstrated back in the 1980s, with considerable research occurring since then on the optimal dose and conditions for use. The role of ASA in the prevention of a second heart attack or other cardiovascular “event” after the first one has occurred is now well established. In this population, the benefits tend to greatly outweigh the risks, and daily ASA therapy is standard treatment. As supporting evidence has emerged, there has been growing enthusiasm for its use in primary prevention, with some guidelines now (cautiously) endorsing its use. Steven Novella reviewed the evidence in a past post, noting that the potential benefit, being small, needs to be weighed against the real risk of side effects.
How ASA prevents colorectal cancer isn’t clear, but it does appear to work. It may be due to its effects on inflammation, possibly reducing the formation of tumors in the colon, but its effects on platelets have also been proposed.
What did the USPSTF do?
The USPSTF commissioned three systematic reviews and a decision analysis model to develop its recommendations. Using benefit and harm data, they estimated overall benefits to different groups. The model started by assuming a population that was not already taking non-steroidal anti-inflammatory drugs (NSAIDs), and with no risk factors for gastrointestinal bleeding. They used a risk calculator to predict the 10-year risk for a heart attack, stroke, or other death due to heart disease. They then considered the likelihood of benefit (cardiovascular events and cancers avoided) versus the risk of harms (e.g., gastrointestinal ulcers, and strokes caused by bleeding in the brain), and how that changed over time. The effects were modest but for some groups, a net benefit was found. ASA can reduce the risk of heart attacks and strokes by about 22%, although effects on all-cause mortality (any reason for death) are more modest (6% based on pooled data). Data on the effectiveness in reducing the risk of colorectal cancer was also observed. However, it takes 10 years or more before a benefit is seen – which can be up to 40%, with a 33% mortality benefit. The longer your life expectancy, the greater chance you have to experience benefit.
The net benefits and risk were then summarized for different age groups.
What are the expected benefits of daily ASA consumption?
Decisions about risks and benefits are ultimately personal ones. In this case, you must weigh your perceptions about the benefit of avoiding colorectal cancer, heart attacks and ischemic strokes against the risks of harms from ASA. The USPTF concluded there was sufficiently good evidence to conclude with “moderate certainty” that the benefits outweigh the risks for those aged 50-59 who are not at an elevated risk of bleeding:
The USPSTF recommends low-dose aspirin use for the primary prevention of cardiovascular disease (CVD) and colorectal cancer in adults ages 50 to 59 years who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years.
They were also supportive, but with somewhat less confidence, of daily ASA used in those aged 60-69:
The decision to use low-dose aspirin to prevent CVD and colorectal cancer in adults ages 60 to 69 years who have a greater than 10% 10-year CVD risk should be an individual one. Persons who are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years are more likely to benefit. Persons who place a higher value on the potential benefits than the potential harms may choose to use low-dose aspirin.
I’m under 50 or over 70 years old, why did the USPSTF say the evidence was “insufficient”?
The USPSTF concluded the evidence was insufficient to assess benefits and harms of primary prevention if you are younger than 50 or over the age of 70.
In those under the age of 50, the risk of cardiovascular disease is lower and the expected benefits have not been well studied. Given the lower risk, the harms likely outweigh any expected benefits. People with shorter life expectancy are less likely to obtain an overall benefit from ASA therapy. That’s why the USPSTF was more supportive of starting ASA in those aged 50-59.
Evidence of benefit in older (>70 years) is also lacking. While the risk of cardiovascular disease is much higher, so is the likelihood of harm from ASA. There is also less expected benefit in terms of protection from colorectal cancer in this age group. Consequently, any decision to treat requires a careful evaluation of expected benefits and potential risks.
Why do I need to take ASA for 10 years? Is there any benefit to taking it occasionally?
The overall benefits of ASA are due to effects on cardiovascular disease and cancer. The evidence suggests you need to take ASA daily for at least 10 years before there’s a meaningful benefit on your risk of colon cancer, which is an important contributor to the overall benefit of the therapy.
What’s the proper dose of ASA for primary prevention?
There’s no clear evidence supporting any single dose. The 81mg tablet is widely available and used regularly. There’s no persuasive evidence that enteric-coated tablets or “buffered” tablets reduce the side effects of ASA. One tablet daily is the usual dose.
What are the possible risks of daily ASA therapy?
The biggest risk of ASA treatment is gastrointestinal (GI) bleeding. The risk of a GI bleed increases with age. Any other conditions or medications that raise that risk (e.g., history of GI ulcer) need to be considered in the overall decision. There is also the risk that the benefits will be reduced if the medication isn’t taken. A decision to start ASA to prevent disease should be considered a 10 year commitment. Sticking with daily medication use can be challenging, particularly when you’re not actually ill.
I don’t want to take ASA, what can I do to reduce my risks?
You can dramatically reduce your risk of cardiovascular disease through lifestyle changes:
- Don’t smoke
- Maintain a healthy body weight
- Exercise regularly
- Eat a healthy diet
You can also add to this:
- Prevent and treat diabetes, high blood pressure and high cholesterol, using the best evidence
Do as many of these as possible and you will significantly reduce your risk of cardiovascular disease.
There’s less evidence to suggest that lifestyle changes can prevent colorectal cancer, but a healthy diet and the advice above will probably be helpful. Screening programs are effective, and should be considered at the appropriate age (usually age 50).
Praise and criticism
Taking ASA for primary prevention requires a close evaluation of known risks and expected benefits. The new USPSTF guidelines try to clarify the place in therapy. Probably the biggest argument against primary prevention with ASA is the fact that there is limited randomized data that’s examined this specific question. This has led to different interpretations of the evidence. As recently as May, the FDA denied a request from Bayer to approve the marketing of Aspirin for primary prevention. Some criticize the guidelines for their complexity, suggesting that some may consider self-medicating without implementing more important (and effective) lifestyle changes or accessing screening programs.
What’s the bottom line?
Given the risks, is the evidence strong enough to recommend ASA for primary prevention? For those in the 50-69 age group, there is likely to be a modest, but real benefit. But this benefit comes with some risks. On an individual basis, the incremental benefit needs to be considered in the context of everything that you’re doing to prevent cardiovascular disease and cancer. Calculate your own cardiovascular risk. Think about what you personally value, your own lifestyle choices, and the risks you’re willing to accept. Then speak with your primary care provider about your preferences.