Special Report:

ACE inhibitors reduce mortality: So why aren't they being used?

These drugs should be first-line treatment for CHF, experts say

More than 10 years after angiotensin-converting enzyme (ACE) inhibitors were first established as the drugs of choice for the treatment of congestive heart failure, recent studies show that physicians continue to seriously underuse them. And this failure to prescribe the drugs is resulting in more deaths, more hospitalizations, and a lower quality of life for countless numbers of patients, experts say.

Randall Stafford, MD, PhD, instructor in medicine at Harvard Medical School and Massachusetts General Hospital in Boston, says ACE inhibitors are the only drugs that can prolong life, alleviate symptoms, and prevent worsening of CHF. He can point to at least five studies published between 1987 and 1995 that prove ACE inhibitors dramatically improve mortality, hospitalization rates, progression of left ventricular dysfunction, exercise tolerance, and symptom severity. Stafford's own study, published recently in the Archives of Internal Medicine, found that only 31% of CHF patients nationwide receive ACE inhibitors.1 By contrast, Stafford contends, at least 50% to 75% of CHF patients should be on the drugs.

"The striking thing about the study is that if you look at any measure of benefit, ACE inhibitors really have a substantial effect," Stafford said. "It was surprising that the numbers were as low as we found. Clearly, there is something wrong. Physicians just aren't using these medications as much as they should." (For possible reasons and solutions, see related stories, pp. 39 and 40.)

Stafford's study, the first to report national patterns of use of ACE inhibitors, looked at data from records of 181,000 patient visits and 9,523 physicians from the 1989-1994 National Ambulatory Medical Care Surveys. Besides finding that just under 31% of patients were using ACE inhibitors in 1994, Stafford also discovered significantly lower use of the drugs among women (23% vs. 29% of men), patients living in the West or South (about 22% vs. 31% in the Midwest and 28% in the Northeast), and patients visiting general practitioners (21% vs. 46% of cardiologists).

Besides the information in the clinical literature about the benefits of ACE inhibitors, guidelines published by the American College of Cardiology and American Heart Association in 1995 and by the Agency for Health Care Policy and Research in 1994 strongly recommend using ACE inhibitors as first-line treatment. The AHCPR guideline states that all patients with heart failure due to left-ventricular systolic dysfunction should be given ACE inhibitors unless they have a history of intolerance to the drugs, serum potassium greater than 5.5 mEq/L that can't be reduced, or symptomatic hypotension. Stafford says that patients with diastolic failure also can benefit from ACE inhibitors but that most of the studies have focused on systolic dysfunction.

ACE inhibitors such as capoten, enalapril, and lisinopril reduce the enzymatic conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that causes blood pressure to increase, says Cindy Nielson, PharmD, pharmacist consultant for cardiovascular medicine at LDS Hospital in Salt Lake City. The drugs reduce volume overload, promote fluid loss, lower blood pressure, and decrease harmful adrenaline levels. Few patients are unable to take the drugs, and most tolerate them well. A common complaint is a dry hacking cough. In rare cases, the drugs can increase creatinine and worsen kidney function.

"It's a slippery slope when they have heart failure and existing kidney disease. The ACE inhibitor is protective within the kidney itself to a certain point, and then it can become damaging," Nielson says. "But most people would agree that it's worth trying the drug because it won't cause permanent damage to the kidney, and it's such a benefit to the heart failure."

Nielson published a study in 1996 that showed ACE inhibitors have another benefit: If given within 24 hours of a heart attack, they can prolong survival, especially if the patient already has signs of heart failure. Nielson analyzed data from six previous trials that included a total of 98,450 heart attack patients, half of whom received ACE inhibitors within 24 hours of the attack and half who received standard care. At the end of a year, 11.94% of the ACE inhibitor-treated patients had died, compared with 12.58% of the other patients.

"After a heart attack, the tissue dies if you don't do something soon enough," she says. "Then you have dead and live tissue together, and there can be slippage. ACE inhibitors help prevent wall stress, site slippage, and ventricular dilation."

Prakash Deedwania, MD, chief of the cardiology division at the Veterans Affairs Medical Center in Fresno, CA, and clinical professor of medicine at the University of California San Francisco School of Medicine, says he's concerned that more clinicians aren't prescribing the treatment that is clearly most appropriate.

"Here we are at least 10 years after it was well-established that ACE inhibitors are the treatment of choice in all patients with CHF and in fact are the only therapy that makes a significant impact," Deedwania says. "Other treatments are helpful, but ACE inhibitors are the only thing that improves symptoms and survival and prevents progression of the disease. It is surprising to see that clinicians are not prescribing them."

What is even more disconcerting, Deedwania says, is that in Stafford's study 15% of the patients were given calcium channel blockers. These drugs have never been shown to help CHF patients and potentially could worsen heart failure and increase mortality, he says. "On the one hand, we have lack of use of the appropriate drug, and on the other hand, we have use of a drug that may hurt," he says. "Calcium channel blockers should only be used for hypertension or angina, but physicians like them because they're so easy to use. You can put the patient on them and forget about it because they don't have very many side effects. But we have to remember as physicians that we are not to use drugs that might do potential harm even if they are well-tolerated. The patient is not going to feel anything's wrong until they have a heart attack, and then it's too late."

[For more information on ACE inhibitors, contact: Randall Stafford, MD, PhD, Massachusetts General Hospital, 50 Staniford St., Ninth Floor, Boston, MA 02114. Telephone: (617) 724-4613. Cindy Nielson, PharmD, LDS Hospital, 8th Ave. and C St., Salt Lake City, UT 84143. Telephone: (801) 321-1257. Prakash Deedwania, MD, UCSF Program at Fresno, 2615 E. Clinton Ave., Fresno, CA 93703. Telephone: (209) 228-5325.]


1. Stafford, "National Patterns of Angiotensin-Converting Enzyme Inhibitor Use in Congestive Heart Failure," Arch Intern Med 1997; 157:2,460-2,464.