Aspirin is one of the oldest drugs out there. And yet researchers are still learning what it can - and cannot - do.
It's clear that daily aspirin can be beneficial for people who have had a heart attack or an ischemic stroke. Scores of studies have shown that this simple treatment reduces the chance of having a repeat heart attack or stroke.
Researchers have long wondered whether the drug might also prevent first heart attacks or first strokes. A new study followed 14,000 Japanese people age 60 and older who had high blood pressure, high cholesterol or diabetes - three major risk factors for atherosclerosis, which can block arteries and cause heart attack and stroke.
The results, published last month in the Journal of the American Medical Association, found no overall benefit to taking an aspirin a day. The study hardly puts the question to rest, however.
The study did find slightly fewer heart attacks and transient ischemic attacks (similar to a stroke, but ending quickly without damage) with aspirin. Indeed, some doctors continue to recommend aspirin as a prophylactic in certain high-risk patients.
One reason the study failed to show an overall benefit was that the control group had surprisingly few cardiovascular events. (It's hard to detect protection against something when it's barely happening in the first place.)
Also, the study found an unacceptable rate of serious side effects in those who took aspirin. Daily aspirin treatment is not risk-free. The same properties that reduce clotting and the buildup of atherosclerotic plaques in blood vessels also increase bleeding risks, including potentially catastrophic bleeding in the brain.
So to show an overall benefit, aspirin use would have to prevent a significant number of initial heart attacks and strokes while causing very few brain bleeds. The latest study failed to meet that standard.
"Where do we draw the line?" asks J. Michael Gaziano, a cardiologist at the VA Boston Healthcare System.
The study results mean that doctors need to use caution in recommending the treatment to patients who have never experienced heart attacks or strokes.
"Some people's risk for [a first] heart attack is as high as someone who has [already] had a heart attack," Gaziano says.
If you've already had a heart attack, the evidence is clear that the benefits of aspirin outweigh the risks, says Robert Califf, a cardiologist at the Duke University School of Medicine in Durham, N.C. "Otherwise, have a conversation with your doctor and make an individual decision."
Gaziano says, "It's a calculation you have to do based on an individual's risk of heart attack and the risk of a serious brain bleed."
Three large trials are underway in the United States to address unanswered questions about aspirin for prevention of cardiovascular events. (Gaziano is leading one of them.)
Another factor that may add weight to the benefit side of the equation: Aspirin may be protective against certain cancers, particularly colorectal cancer. The National Cancer Institute is sponsoring research studies to learn more.
Aspirin has other uses, of course. It's a cheap and effective drug for relieving pain, reducing fever and fighting inflammation. For these run-of-the-mill purposes, a suite of drugs competes with aspirin, including ibuprofen (Advil, Motrin), which may be more effective for certain kinds of pain and somewhat less likely to cause stomach upset.
For pain and fever, acetaminophen (Tylenol) doesn't produce the stomach upset that some people experience with aspirin. For arthritis pain, naproxen (Aleve, Naprosyn) is longer-lasting, allowing patients to take just one or two doses a day.
But for prevention of heart attack and strokes, aspirin shines compared with these other drugs. That's because of the way it interacts with platelets in the blood to make them less likely to clot.
"Aspirin permanently blocks the platelet enzyme, for the life of the platelet," Gaziano says. "Ibuprofen only does it transiently, so it doesn't have the sustained action of aspirin."
That means that platelets can be thoroughly inhibited even with a once-a-day dose. (Tylenol does not have anti-platelet action at all.)
Newer platelet-inhibitor drugs have been developed, such as clopidogrel (Plavix), but they haven't unseated aspirin for preventing heart attacks. However, Plavix is a useful alternative, especially in patients who can't take aspirin because they are allergic or have an elevated risk of gastrointestinal bleeding.
Another question about aspirin's preventive powers is what dose is best. For people who can benefit from daily aspirin treatment, the American Heart Association recommends taking a baby aspirin, which contains 81 milligrams, about a quarter of the amount in a regular aspirin tablet (325 milligrams). But a recent study revealed that only a third of people using aspirin daily after a hospital stay were taking the low-dose version.
"Baby aspirin is recommended, but cardiologists are not acting like they believe it," Califf says. He is on a team launching a study to test low-dose-vs.-high-dose aspirin in patients with a history of heart attack or stroke.
Califf says that aspirin is one of the most common things patients ask their doctors about. "It's frustrating to say we don't really know."