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New guidelines refine aspirin prescription

JUN 2009

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Task force offers recommendations for women and guidance on dosage.

Aspirin was once used mainly to relieve pain, ease fever, and get rid of hangovers. Today it's best known for its ability to protect hearts. This hundred-year-old drug is a mainstay for treating heart attacks, and it also helps ward off heart attacks and the most common kind of stroke. But limited evidence on aspirin's preventive effects has made it difficult for experts to give encompassing recommendations about who benefits from daily aspirin and how much to take. One consequence of this uncertainty is public confusion about aspirin. Some of the 50 million Americans who take aspirin for their hearts' sake shouldn't be taking it; others who need aspirin aren't taking it.

Updated recommendations from the U.S. Preventive Services Task Force fill in two big gaps — about aspirin for women and about the safest dose to take (Annals of Internal Medicine, March 17, 2009). But the recommendations don't provide a cookie-cutter approach. Instead, they emphasize weighing the benefits of aspirin therapy against the risks. This isn't differential calculus, but it does require a few numbers, some thought, and input from a trusted physician to make a good decision.

Key points

  • Aspirin can help prevent first heart attacks in men and first strokes in women. Age and risk factors determine who benefits from taking an aspirin a day.

  • For prevention, a baby aspirin a day (an uncoated 81-milligram tablet) offers good protection with the least stomach irritation.

Aspirin's balance sheet

Every drug can do both good and harm. Aspirin can prevent heart attacks and strokes. It can also irritate the stomach and cause unwanted — and sometimes serious — bleeding. The positive and negative effects stem from aspirin's inactivation of an enzyme called cyclooxygenase-1 (COX-1). Here are both sides of the ledger:

In the black: COX-1 helps blood cell fragments called platelets make a signaling molecule called thromboxane A2. Think of this molecule as the glue that makes platelets stick together when they are activated by inflammation or injury. By blocking COX-1, aspirin turns off platelets' ability to make thromboxane A2. Without it, they have a hard time clumping together, an early step in the formation of blood clots. Fewer clots means fewer heart attacks and strokes. Why? Patches of cholesterol-laden plaque embedded in the lining of blood vessels sometimes rupture. As the contents of the plaque drift into the bloodstream, platelets congregate at the break. Their clumping, and the clot that forms around them, help seal the broken plaque. However, if the clot blocks blood flow through the vessel, it can cause a heart attack or stroke.

In the red: In the digestive tract, COX-1 makes hormone-like compounds called prostaglandins. Prostaglandins help protect cells in the lining of the stomach and intestines from the corrosive action of acids and digestive enzymes. By blocking COX-1, aspirin turns down the production of prostaglandins. This can lead to anything from a mild feeling of heartburn to bleeding ulcers. Since aspirin also makes it more difficult for blood to clot, a bleeding ulcer can lead to serious blood loss. The other downside of aspirin use is an increased risk of bleeding (hemorrhagic) stroke. This type of stroke occurs when a blood vessel in the brain bursts. By interfering with blood clotting, aspirin can promote hemorrhagic strokes or make them worse. Hemorrhagic strokes are less common than ischemic strokes, accounting for about 20% of all strokes, but they tend to be more damaging than ischemic strokes.

Should you take aspirin?

In general, you should consider taking aspirin if its benefits outweigh its risks. That may sound like a wishy-washy recommendation, but it's the real bottom line. For men, the main benefit is preventing a heart attack. For women, it is preventing a stroke. For both, the risks are gastrointestinal bleeding and hemorrhagic stroke.

The simplest way to figure your heart disease or stroke risk is by using one of several online calculators, such as the Framingham or Reynolds risk scores. We've listed several of these calculators at health.harvard.edu/147. They give you a percentage. Say yours is 13%. It means that for every 1,000 people with risk factors like yours, 130 will have a heart attack or stroke over the next 10 years.

Now compare your cardiovascular risk with the chance that taking aspirin will lead to gastrointestinal bleeding or cause a hemorrhagic stroke. As with heart disease, this risk increases with age. The estimates of these complications look like this: before age 59, 0.9% for men and 0.5% for women; from 60 to 69, 2.5% for men and 1.3% for women; and from 70 to 79, 3.7% for men and 1.9% for women. Several things boost the chances of getting into trouble with aspirin:

  • Regular use of ibuprofen (Advil, generic) or another nonsteroidal anti-inflammatory drug in addition to aspirin increases the risk of gastrointestinal bleeding fourfold.

  • Men are twice as likely as women to have gastrointestinal bleeding.

  • Having had a gastrointestinal ulcer, gastrointestinal bleeding, or hemorrhagic stroke increases the chances it will recur.

  • Uncontrolled high blood pressure or use of an anticoagulant such as warfarin (Coumadin, Jantoven, generic) also increases the risk for a hemorrhagic stroke or serious bleeding.

Here's how to put this information together. Say you are a 68-year-old woman with a stroke risk of 18%. By taking aspirin every day, you lower your risk by 25%, to 13.5%. (That translates into 45 fewer heart attacks or strokes for every 1,000 folks taking low-dose aspirin.) Your chance of having a problem with aspirin is 1.3%. The benefits definitely outweigh the risks.

What about a 55-year-old man with a 10-year heart attack risk of 2%? Taking aspirin would lower it by 25%, to 1.5%. Since he takes ibuprofen for his arthritis, his chance of having a problem with aspirin is close to 4%. For him, the risk is higher than the benefit.

The task force sets several tipping points, based on age and sex (see "Aspirin's balancing act"). Although these numbers are helpful, they're very impersonal. Someone who cared for a parent who suffered a disabling stroke may want to do everything possible to avoid having a stroke, and would take the risk of gastrointestinal bleeding as an acceptable gamble. These are the kinds of things your doctor can help you work through, with the numbers as a starting point.

Aspirin's balancing act

Diagram of benefits and risks of aspirin based on age and sex

Taking aspirin to prevent a heart attack or stroke isn't for everyone. It makes the most sense if your chance of having a heart attack or stroke (calculated online or with your doctor) is greater than the odds of it causing a problem. For example, a 65-year-old woman with a 20% chance of having a stroke over the next 10 years is a good candidate for aspirin, since her potential for having a problem with aspirin is low (about 8%).

Best dose

Trials evaluating the cardioprotective effect of aspirin have tested doses ranging from 500 milligrams (mg) a day to 100 mg every other day. The task force says there still isn't enough evidence to say for certain which one is best. But it concludes that a dose of 81 mg a day, the amount in a baby aspirin, seems to work just as well as higher doses, with fewer bleeding problems.

Taking aspirin with a protective coat that helps it get through the stomach without being broken apart sounds like a great idea for preventing stomach irritation. But it doesn't work. Aspirin in the bloodstream irritates the stomach just as much, and there's some evidence that not all of the aspirin in a coated pill gets into the circulation. For prevention, the best bet is to take a child's chewable aspirin. These deliver 81 mg of aspirin without a coating. A store-brand version is just as good as a name brand, and costs less.

If you routinely use ibuprofen or other nonsteroidal anti-inflammatory drug, there are two things to consider. Combining these with aspirin increases the chances of stomach irritation and bleeding. Talk with your doctor about using an acid blocker to prevent this problem. In addition, nonsteroidal anti-inflammatory drugs can block aspirin's ability to keep platelets from clumping. It's best to take aspirin in the morning, then wait at least 30 minutes before taking ibuprofen. If that's impossible, try to delay taking aspirin for at least 8 hours after taking ibuprofen.

Beyond aspirin

Aspirin isn't a miracle worker. It lowers the chances of having a first heart attack or stroke by 25%, which is great, but it means you can't rely on aspirin alone to protect you. If you're really serious, there's a lot more you can do. The combination of not smoking, maintaining a healthy weight, exercising daily, choosing a healthful diet, and drinking alcohol in moderation lowers the risk of having a heart attack or stroke between 50% and 80%.

As one wag has said, if you plan to take aspirin every day to prevent a heart attack or stroke, take it for a long walk before you swallow it.