Even though certain medications such as ACE inhibitors reduce the risk of death for patients with heart failure, patients at greatest risk often are not prescribed these medications, according to an article in the September 14 issue of JAMA.

Heart failure affects more than 5 million people in Canada and the United States and is associated with a high death rate, according to background information in the article. Medications shown to reduce the risk of illness and death from this condition include angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), and beta-adrenoreceptor antagonists. These drug classes have been studied extensively and recommended strongly by disease management guidelines, given their proven benefit of reducing the risk of death in patients at the highest risk. It might be expected that these individuals would be more likely to receive these medications. However, previous studies have suggested that the opposite may occur in practice.

Douglas S. Lee, M.D., Ph.D., of the University of Toronto, and colleagues examined the use of drug therapies for heart failure in relation to predicted 1-year death rates. The patients for this study were part of the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study (1999-2001), which included 9,942 hospitalized patients with heart failure. The researchers evaluated 1,418 patients, aged 79 years or younger, with documented left ventricular ejection fraction (a measure of the heart's pumping ability) of 40 percent or less and with low-, average-, and high-predicted risk of death within 1 year. All patients survived to hospital discharge. Administration of ACE inhibitors, ACE inhibitors or ARBs, and beta-adrenoreceptor antagonists were evaluated according to predicted risk of death.

The researchers found that at hospital discharge, prescription rates for patients in the low-, average-, and high-risk groups were 81 percent, 73 percent, 60 percent, respectively, for ACE inhibitors; 86 percent, 80 percent, 65 percent, respectively, for ACE inhibitors or ARBs; and 40 percent, 33 percent, 24 percent, respectively, for beta-adrenoreceptor antagonists. Within 90 days following hospital discharge, the prescribing rates were 83 percent, 76 percent, and 61 percent for ACE inhibitors; 89 percent, 83 percent, and 67 percent for ACE inhibitors or ARBs; and 43 percent, 36 percent, and 28 percent for beta-adrenoreceptor antagonists for the three risk groups, respectively. The pattern of lower rates of drug administration in those patients at increasing risk was maintained up to 1 year postdischarge.

After accounting for varying survival time and potential contraindications to therapy, low-risk patients were 61 percent more likely to receive ACE inhibitors or ARBs; and 80 percent more likely to receive beta-adrenoreceptor antagonists compared with high-risk patients.

"A potential explanation for the inverse relationship between risk and treatment rates could be under appreciation of the benefits of therapy, particularly in patients with chronic disease who are at risk of death from noncardiac causes," the authors write. "Additionally, clinicians may be distracted from heart failure care in patients with multiple comorbid [coexistence of two or more often related diseases] conditions. However, despite excluding patients with several potential life-limiting comorbidities, the treatment mismatch remained. The possible need for multiple prescription medications could also be a consideration in withholding therapy."

"In conclusion, the predicted and observed risks of death in patients with heart failure were inversely associated with discharge and postdischarge administration of potentially life-saving drug therapies. This finding is particularly important because patients at highest risk of death have great need for effective treatment. Clinical use of quantitative multifactorial risk profiles or algorithms that convey information regarding probability of poor outcomes could be applied to better identify such patients. Further study is needed to quantify the adverse consequences attributable to the mismatch between risk and treatment rates and may also identify potential solutions to correct this undesirable phenomenon," the researchers write.