The difference could as much as about 45 percent, mostly due to less risk of blood clots, heart attack and strokes, and perhaps from other causes, the researchers say.
The study was conducted by Dr. Patricia Gum and her colleagues at the Cleveland Clinic. The findings appear in the Sept. 12 Journal of the American Medical Association.
While aspirin's ability to prevent heart attacks is well known, studies have been less conclusive about its effects on overall mortality. One reason, however, may have less to do than the drug itself than in the way researchers tested it.
Randomized trials, the gold standard for clinical research, can understate the powers of a given drug because subjects in these studies typically are healthier than the average patients a physician treats. As a result, many patients may not seem to be eligible for a given therapy.
In the latest study, a so-called "observational" analysis, Gum's team compared death rates and aspirin use among nearly 6,200 patients undergoing stress tests at hospitals between 1990 and 1998 to detect heart disease. Of those, 2,310, or 37 percent, were taking low-dose aspirin therapy to prevent heart attacks.
Over the next three years, 4.5 percent of patients in each group died, suggesting no impact from aspirin on overall mortality. However, when Gum's group adjusted for a variety of factors, including age, history of heart disease, ability to exercise and heart function, people taking aspirin had a 33 percent lower risk of death than those not on the drug.
The researchers next adjusted their data using a statistical tool called "propensity analysis," to better compare outcomes in patients on and off aspirin. This time, aspirin appeared to cut the odds of dying by about 45 percent.
Aspirin was most beneficial to older patients, those with more feeble heart function and those with a history of coronary artery disease, the researchers say.
While the effects of aspirin on overall mortality appear to be a cause-effect relationship, the researchers caution that the nature of their study makes that kind of statement tricky.
Still, study co-author Dr. Michael Lauer, a Cleveland Clinic cardiologist, says despite it's limitations, the study has important implications for patients. "I very much hope that it's going to change clinical practice," he says.
Patients who don't get adequate exercise -- about 90 percent of Americans over age 50 -- stand to gain the most from the results, says Lauer. "We know that people who are physically unfit have substantially higher death rates, but they also have blood that clots much more easily," a problem aspirin helps control by preventing cells called platelets from clumping.
The findings should encourage more doctors to prescribe aspirin to their patients with established heart problems, Lauer says. While experts recommend aspirin to prevent second heart attacks, a study last year found that only 26 percent of patients with heart disease received the drug.
Since the Cleveland study was observational, not randomized, the scientists say they weren't able to account for every difference between aspirin users and other subjects.
Randomized trials have the added advantage of allowing scientists to maximize the benefit of an intervention to patients while minimizing their risk of harm. Observational studies, on the other hand, are simply a comparison across time leading to a given outcome, such as death.
But heart experts defended the study method. "What we needed was a large enough sample to detect this difference, which is the strength of observational studies," says Dr. Paul Heidenreich, a Stanford University cardiologist.
"The observational studies also include all patients and thus are studies of true effectiveness. The results should make clinicians comfortable in prescribing aspirin to patients at risk for coronary disease that would not have been candidates for the randomized trials," Heidenreich says.
Christiana Drake, a statistician at the University of California at Davis, says propensity analysis can be a useful device, but it can only handle variables that researchers already understand. "If I know that age should be adjusted for, but I have no data on age for my study subjects, I have a problem," Drake says.
Similarly, if scientists turn up a new factor five years in the future, "my study is in doubt because I have no information on [that variable], so I cannot check whether or not it needed adjustment," Drake says.
What To Do
For more on the use of aspirin to prevent heart attacks and strokes, visit the American Heart Association.
To learn more about cardiovascular care, try the National Institutes of Health.