Tuesday, June 26, 2007

Trial results highlight challenges, opportunities for treating women with ischemic heart disease
by Jonathan McCall, DCRI Communications

Ischemic heart disease (IHD), a condition in which blood flow to the heart muscle is restricted or blocked, is a leading cause of death in both men and women. But although more women die from IHD each year than men, most clinical trials of acute coronary syndromes have much higher enrollments for men than for women. A number of clinical studies have also demonstrated that women are less likely than men to receive recommended therapies, despite their higher overall level of risk.

Robert Harrington, MD

Such shortcomings in treatment clearly need to be addressed by researchers and clinicians. However, tackling this problem is complicated, and the correct answers may not be obvious at first, cautions DCRI director Robert Harrington, MD. In an editorial appearing in the June 5 issue of Circulation, Dr. Harrington describes the challenges of mapping an effective approach to treating IHD in women, some of which may arise from actual differences in the biology of the disease in women as compared to men.

There is widespread agreement among experts that a cornerstone of treatment for IHD is the use of antithrombotic drugs. These drugs help prevent the formation of clots than can block blood vessels, shutting down the flow of blood and causing a heart attack. But, notes Harrington, the use of antithrombotic drugs comes with a danger of its own: an increased risk for bleeding and certain kinds of stroke. Recent studies of such drugs have suggested that they may have different effects when used in women and men. This in turn has raised questions about the balance of risks and benefits for using such drugs in women.

Harrington also points out that other research has made the question even more complex. A series of studies of the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC and AHA Guidelines (CRUSADE) registry performed by the DCRI's Dr. Karen Alexander has suggested that physicians often over-dose the amount of antithrombotic drugs a patient needs, increasing the risk of dangerous side effects such as bleeding. This may be particularly dangerous for women with IHD, who tend to be older and to weigh less than men, and who are more likely to suffer from conditions such as chronic kidney disease that increase the risk of bleeding even further.

These issues highlight the importance of the results of the Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Treatment–Thrombolysis in Myocardial Infarction (ExTRACT-TIMI 25) trial, published in the same issue of Circulation. As is often the case, most ExTRACT-TIMI 25 subjects were men. However, due to the overall size of the trial, a relatively large group of women were enrolled as well. The study, which compared the use of two different antithrombotic medications (unfractionated heparin and enoxaparin), confirmed a number of findings from previous clinical trials: women tended to have worse overall outcomes than men and received fewer evidence-based treatments.

However, the study also suggested that women who received antithrombotic drugs had their risk of death or recurrent myocardial infarction reduced by about the same rate as men. Also, an examination of the rates of bleeding among both women and men suggested that careful dosing of antithrombotic medications may be key to effectively balancing the risks and benefits of these drugs.

Unfortunately, the number of women in the ExTRACT study, while large enough to suggest interesting possibilities, was not large enough for investigators to draw firm conclusions. But, as Dr. Harrington emphasizes, the results help to shine a spotlight on the potential for additional data and better evidence-based therapies to improve the care of both women and men with IHD.