ACC report: Higher lisinopril dose reduces CHF mortality
ACC report: Higher lisinopril dose reduces CHF mortality
Why aren't ACE inhibitors prescribed for more CHF patients?
A new study presented at the American College of Cardiology meeting in Atlanta in April showed that high doses of the angiotensin-converting enzyme (ACE) inhibitor lisinopril (Zestril, Zeneca Pharmaceuticals, Wilmington, DE) may help congestive heart failure (CHF) patients live longer and be hospitalized less. "If you took every patient with heart failure on a low dose of an ACE inhibitor and instead treated them with a high dose, each year we would prevent 250,000 hospitalizations for heart failure," said Milton Packer, MD, of the Center for Heart Failure Research at Columbia-Presbyterian Medical Center in New York City at the meeting. The reduction in hospitalizations would save $2 billion a year. Packer led the five-year international trial that compared the effect of high (30-35 mg/d) to low (2.5-5 mg/d) doses of lisinopril on mortality and morbidity in 3,000 patients with CHF. The higher dose was shown to reduce the combined risk of death from all causes and hospitalizations by 12%. The medication typically is well-tolerated except for a slightly higher incidence of dizziness and worsening of renal function.
Not only are physicians prescribing that particular ACE inhibitor in doses too small, but they are underusing the agents in general, and this comes more than 10 years after ACE inhibitors were first established as the drugs of choice for the treatment of CHF. Recent studies show physicians continue to under-prescribe them in any dosage, resulting in more deaths, more hospitalizations, and a lower quality of life for countless patients. The medications cost on average $390 per year per patient.1
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. Several studies published over the past 10 years prove that they dramatically improve mortality and hospitalization rates, progression of left ventricular dysfunction, exercise tolerance, and symptom severity. Stafford's own study found that only 31% of CHF patients nationwide receive ACE inhibitors.2 He contends that at least 50%-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 says. "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 story, p. 71.)
Stafford's study, the first to report national patterns of ACE inhibitor use, 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, patients living in the West or South, and patients visiting general practitioners vs. cardiologists.
A 1993-1994 chart review of hospitalized geriatric CHF patients across 10 states also showed widespread underuse of ACE inhibitors, with variations both by age and state of hospitalization.3 The investigators reviewed 6,700 medical records of Medicare patients hospitalized with a principal diagnosis of heart failure not due to valvular disease, endocarditis, or myocarditis. Data indicated an improvement in the use of ACE inhibitors to an overall rate of 55% at hospital discharge, but that is still far less than the desired usage. Analyzed by age, usage was 59% among the 65- to 74-year-old age group and only 50% in the group age 85 and older.
The study also demonstrated a difference in length of stay for the CHF diagnosis, ranging from a median of four days in California and eight days in New Jersey, showing regional differences in the treatment of this disease.
Just look at the guidelines
Besides the information in the clinical literature about the benefits of ACE inhibitors, established guidelines recommend their use. The 1995 guidelines published by the American College of Cardiology in Bethesda, MD, and the American Heart Association in Dallas and the 1994 guideline by the Agency for Health Care Policy and Research (AHCPR) in Rockville, MD, strongly suggest using ACE inhibitors as first-line treatment. The AHCPR guideline (available at http://www. ahcpr.gov on the Internet) 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.4 Stafford says patients with diastolic failure also can benefit from ACE inhibitors but that most of the studies have focused on systolic dysfunction. (See article on how a disease management firm got physicians to implement the AHCPR guidelines, p. 71.)
ACE inhibitors reduce the enzymatic conversion of angiotensin I to angiotensin II, a potent vasoconstrictor that causes blood pressure to increase, says Cindy Nielson, PharmD, a pharmacist consultant for cardiovascular medicine at LDS Hospital in Salt Lake City, UT. 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, although a common complaint is a dry hacking cough. In rare cases, the drugs can increase creatinine and worsen kidney function.
After a heart attack, Nielson says, the tissue dies if you don't correct the situation quickly. ACE inhibitors help prevent wall stress, site slippage, and ventricular dilation. Heart failure and existing kidney disease, however, can present a slippery slope - the ACE inhibitor is protective within the kidney itself to a certain point, and then it can become damaging. "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," she says.
Underuse 'disconcerting'
Prakash Deedwania, MD, chief of the cardiology division at the Veterans Affairs Medical Center in Fresno, CA, 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 only ACE inhibitors improve symptoms and survival and prevent progression of the disease, he says. "It is surprising to see that clinicians are not prescribing them."
What is even more disconcerting, he says, is that Stafford's study revealed that 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 be used only for hypertension or angina, "but physicians like them," he says, "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."
References
1. Chang W, Ward RD, McCarthy BD. The cost-effectiveness of increased utilization of angiotensin converting enzyme inhibitor therapy for patients with congestive heart failure. Health Services Research: Implications for Policy, Management and Clinical Practice, 1993 AHSR Annual Meeting Abstracts; Paul SD, et al. Costs and effectiveness of angiotensin converting enzyme inhibition in patients with congestive heart failure. Arch Intern Med 1994;154:1143-1149.
2. Stafford RS, Saglam D, Blumenthal D. National patterns of angiotensin-converting enzyme inhibitor use in congestive heart failure. Arch Intern Med 1997;157:2,460-2,464.
3. The Large State Peer Review Organization Consortium. Heart failure treatment with angiotensin-converting enzyme inhibitors in hospitalized Medicare patients in 10 large states. Arch Intern Med 1997;157:1103-1108.
4. Konstam M, et al. Heart failure: Evaluation and Care of Patients With Left Ventricular Systolic Dysfunction. AHCPR Publication No. 94-0612. Rockville, MD: Agency for Health Care Policy and Research, June 1994; 1-21.
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