Important new lessons learned from aspirin

Sep 20 2005

No other medicine is as common, inexpensive, and yet powerful in so many ways as aspirin; yet despite a century of experience with the drug, researchers are still learning important new lessons, while raising new questions, according to seven special articles in the Sept. 20, 2005, issue of the Journal of the American College of Cardiology.

As Franz H. Messerli, M.D., F.A.C.C., from St. Luke's-Roosevelt Hospital Center in New York, noted in an editorial, "Today, about 50,000 tons of acetylsalicylic acid are produced every year across the globe. If this entire output were pressed into 500 mg tablets, it would amount to 100 billion tablets every year."

Dr. Messerli also remarked, "[W]ere aspirin discovered today, it would probably not pass muster at the Food and Drug Administration for any indication without a black box warning."

Aspirin May Be Safer than Thought for Heart Failure Patients with Coronary Artery Disease

Although aspirin is strongly recommended for most people at high risk for heart attacks, there have been concerns it may be harmful for heart failure patients, because aspirin might interfere with ACE inhibitor treatment or it might worsen hypertension or kidney problems. However, the largest study of the issue, a new analysis of Medicare records on 24,012 patients who had been hospitalized for heart failure with coronary artery disease, indicates that those prescribed aspirin (54 percent of the total) fared as well or better than those not prescribed aspirin.

"This study suggests that aspirin use in patients with coronary artery disease and coexisting heart failure is not harmful and may result in lower mortality rates. Furthermore, there was no evidence that aspirin use attenuated the beneficial effects of ACE inhibitors," said Frederick A. Masoudi, M.D., M.S.P.H., F.A.C.C., from the Denver Health Medical Center and the University of Colorado Health Sciences Center in Denver, Colo. and the Colorado Foundation for Medical Care in Aurora, Colo.

However, Dr. Masoudi noted that while the study accounted for differences between the patients taking aspirin and those who were not, there may have been other important differences they couldn't identify. Still, Dr. Masoudi said it appears aspirin is under-used.

"Improving the use of aspirin in patients with coronary artery disease is potentially a low-cost means of improving outcomes," Dr. Masoudi said.

James E. Udelson, M.D., F.A.C.C., from Tufts-New England Medical Center, who was not connected with this study, noted that along with the longstanding concerns about aspirin's potential to harm heart failure patients, there is also the possibility that withholding aspirin could deprive certain patients of aspirin's cardiovascular benefits.

"This paper by Masoudi and colleagues adds support to the concept that aspirin has a very beneficial effect in patients with both heart failure and also coronary artery disease, in a study of a very large number of patients. While the retrospective nature of the investigation adds some limitations to the strengths of the conclusions, the data suggest that physicians should not withhold aspirin from such patients," Dr. Udelson said.

However, Barry M. Massie, M.D., F.A.C.C., from the University of California, San Francisco and the San Francisco VAMC, struck a more cautious tone in an accompanying viewpoint article, noting that the only two prospective randomized trials of this topic suggest that aspirin may be associated with worsening heart failure in some patients. The studies reported 30 percent higher rates of hospitalization among patients on aspirin compared to those receiving warfarin or no therapy. This difference might be explained by the inhibition of prostaglandins, which play a role in counterbalancing the adverse effects of neurohormonal activation on blood flow and, possibly, kidney function in heart failure patients.

"These observations suggest that the use of aspirin in heart failure patients should be limited to those with definite indication such as documented coronary disease, and that the dose should be no more than 162 milligrams daily. This is the current recommendation of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy. Furthermore, I personally would consider alternative anti-thrombotic agents in a small group of coronary patients with advanced symptoms or repeated hospitalizations for heart failure" Dr. Massie said.

Barry Greenberg, M.D., F.A.C.C., from the University of California, San Diego, who was not connected with the research, said the use of aspirin in patients with heart failure remains controversial.

"Unfortunately, none of the available studies provides a definitive answer to this question. In this context, the two articles add to the debate," Dr. Greenberg said.

Prior Aspirin Use May Not Be a Red Flag for Heart Attack Patients

Although aspirin can lower the risk of a heart attack, a number of studies have indicated that when someone has a heart attack despite taking aspirin, the outlook may be worse than for a similar patient who had not been taking aspirin before the heart attack. But researchers who analyzed Medicare records on more than 100,000 heart attack patients report that they did not see any link between prior aspirin use and death rates within six months.

"Our findings contrast with some, but not all, previous studies. No prior study, however, had the opportunity to examine the real world experience of a nationally representative group of patients, rather than a selected group who were in a clinical trial or a small observational study," said Harlan M. Krumholz, M.D., S.M., F.A.C.C., from the Yale University School of Medicine in New Haven, Conn. "For the public, this study may reinforce the value of aspirin for the prevention of heart disease: patients who were on aspirin when they had their heart attack had a lower risk of death from their heart attack."

John Alexander, M.D., at the Duke University Medical Center in Durham, N. C., who was not connected with this study, agreed that the apparently divergent results between this analysis and earlier studies might be related to differences in the type of patients involved in research trials and those treated in routine clinical practice.

"The fact that prior aspirin use was not predictive of subsequent events in their analysis, whereas it has been in many others, does call into question whether prior aspirin use really is a marker of risk; but I don't think it settles the question," Dr. Alexander said.

Simon R. Kennon, M.D., at The Heart Hospital, London in London, United Kingdom, who also was not connected with the research team, agreed that the study results challenge the idea that prior aspirin use indicates that a heart attack is at higher risk.

"This should lay to rest the suggestion that prior aspirin use predicts poor outcome in such patients and raises questions about its use in risk scoring models," Dr. Kennon said.

Aspirin at Night May Lower Blood Pressure

Aspirin's effect on blood pressure may depend on when patients take their pills. Researchers in Spain randomized 328 patients with mild hypertension to take a low-dose (100 milligram) aspirin pill each morning, take the pill before bed, or not take aspirin at all. After three months, blood pressure rose slightly among the patients taking aspirin in the morning, but it fell in the group taking aspirin at night. The group that did not take aspirin saw a slight decline in blood pressure, but the difference was not statistically significant.

"The major result from this study is that aspirin selectively decreases blood pressure as a function of the timing of its administration in relation to the rest-activity cycle of each individual subject," wrote the study authors, including Ramón C. Hermida, Ph.D., from the University of Vigo in Vigo, Spain.

The researchers called for further studies to see if there are other benefits from taking low-dose aspirin before bed, instead of in the morning.

Joseph V. Messer, M.D., M.A.C.C., from Rush University Medical Center in Chicago, Ill., who was not connected with this study, said the results again demonstrate the extraordinary value of aspirin, one of the least costly medications.

"Given the widespread use of aspirin, the prevalence of hypertension, and the ease in altering the time of aspirin administration, these results should be widely disseminated," Dr. Messer said.

Franz H. Messerli, M.D., F.A.C.C., from St. Luke's-Roosevelt Hospital Center in New York, commented on the possible antihypertensive properties of aspirin in an editorial in the journal.

"I am a bit doubtful that this is as simple as the authors describe it; but if indeed aspirin taken at bedtime did lower blood pressure, the implications would be tremendous," Dr. Messerli said. "But clearly it will have to be confirmed and re-confirmed before it has any major clinical significance."

While Dr. Messerli said it is too early to recommend low-dose aspirin as a blood pressure treatment, he doesn't see any harm in people who are already taking aspirin switching from taking it in the morning to taking the pill at night. However, he pointed out that people have a harder time remembering to take medications at night, so they may be more likely to miss doses.