Editorials

ACE Inhibitor Therapy: Benefits and Underuse



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Am Fam Physician. 1999 Jan 1;59(1):35-.

During the past decade, several landmark trials have confirmed the benefits of angiotensin converting enzyme (ACE) inhibitor therapy for use in patients with heart failure and patients with recent acute myocardial infarction. Despite the strongly favorable evidence and guideline recommendations, ACE inhibitor therapy remains underused. This editorial reviews the benefits of ACE inhibitor therapy and recent studies describing its lack of utilization in patients and emphasizes the need for broader use of ACE inhibitor therapy.

The clinical impact of heart failure is devastating, and the incidence of this disease has increased steadily in recent years. In the United States, approximately 4.9 million patients (2.5 million men and 2.4 million women) have congestive heart failure.1 About 400,000 new cases of heart failure are reported every year, and it is the single most frequent cause of hospitalization for persons 65 years of age or older. The five-year mortality rate for those with heart failure approaches 50 percent, and more than one half have underlying coronary artery disease.2 This year, an estimated 700,000 persons in our country will survive a myocardial infarction, and 20 percent will be disabled by heart failure within six years. It was estimated that the direct and indirect costs of treating patients with congestive heart failure in the United States in 1998 was $20.2 billion.1

ACE inhibitors are the only medical therapy to date that has been shown in multiple large trials to improve symptoms and prolong life in patients with congestive heart failure. In the past, digoxin, diuretics and vasodilator therapy formed the primary basis for the treatment of heart failure, but now ACE inhibitors are accepted as the mainstay of therapy. A meta-analysis3 of 32 randomized clinical trials studying ACE inhibitor therapy in patients with symptomatic heart failure confirmed their benefit in reducing mortality and recurrent hospitalization for heart failure. Results of the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial4 show improved survival for patients with moderate heart failure who are treated with ACE inhibitors; the results suggest that treatment of 1,000 such patients for three years will prevent 50 deaths and 350 hospitalizations.

ACE inhibitor therapy has also been shown to improve survival in patients with acute myocardial infarction. A meta-analysis5 of eight randomized trials enrolling more than 100,000 patients confirmed a reduction in mortality in those who received oral ACE inhibitors within 24 hours after admission. Among selected patients with a left ventricular ejection fraction of less than 40 percent, anterior infarction or clinical signs of congestive heart failure who are treated with ACE inhibitors for one to four years, a survival benefit of 42 to 76 lives per 1,000 treated patients has been observed.

Major guideline statements emphasize the importance of ACE inhibitor therapy for the treatment of patients with heart failure and those with acute myocardial infarction. The Agency for Health Care Policy and Research clinical practice guidelines for the evaluation and care of patients with heart failure secondary to left ventricular systolic dysfunction6 state the following:

“Patients with heart failure due to left ventricular systolic dysfunction should be given a trial of ACE inhibitors unless specific contraindications exist: (1) history of intolerance or adverse reactions to these agents, (2) serum potassium greater than 5.5 mEq per L that cannot be reduced or (3) symptomatic hypotension. Patients with systolic blood pressures of less than 90 mm Hg have a higher risk of complications and should be managed by a physician experienced in using ACE inhibitors in such patients. Caution and close monitoring are also required for patients who have a serum creatinine level greater than 3.0 mg per dL or an estimated creatinine clearance of less than 30 mL per minute; one half of the usual dose should be used in this setting.”

The American College of Cardiology/American Heart Association guidelines for the management of patients with acute myocardial infarction7 recommend ACE inhibitor therapy in the following situations:

“Patients within the first 24 hours of a suspected acute myocardial infarction with ST-segment elevation in two or more anterior precordial leads or with clinical heart failure in the absence of significant hypotension or known contraindications to the use of ACE inhibitors.”

“Patients with myocardial infarction and a left ventricular ejection fraction less than 40 percent or patients with clinical heart failure on the basis of systolic pump dysfunction during and after convalescence from acute myocardial infarction.”

“When there are no patient complications and no evidence of symptomatic or asymptomatic left ventricular dysfunction by four to six weeks, ACE inhibitors can be stopped. ACE inhibitors should not be used if systolic blood pressure is less than 100 mm Hg, if clinically relevant renal failure is present, if there is a history of bilateral stenosis of the renal arteries, or if there is known allergy to ACE inhibitors in postinfarction patients.”

Despite these strong guideline recommendations, several studies document underuse of therapy with ACE inhibitors in patients who have had a recent myocardial infarction and in those with systolic heart failure.810 The Cooperative Cardiovascular Project (CCP) pilot study8 in Medicare patients surviving acute myocardial infarction revealed that more than 40 percent of those who were candidates for ACE inhibitor therapy based on current guidelines did not receive treatment on discharge from the hospital.

Recently, Stafford and colleagues9 evaluated national patterns of use of ACE inhibitor therapy for patients with congestive heart failure by reviewing data from the National Ambulatory Medical Care Surveys from 1989 through 1994. Despite the proven efficacy of ACE inhibitor therapy for congestive heart failure, less than 31 percent of patients who were candidates received therapy. In the largest study of practices among United States physicians to date, Sueta and colleagues10 evaluated data on the use of ACE inhibitor therapy in 16,576 patients with heart failure that were derived from a national database of cardiology and multispecialty practices. Overall, 50 percent of patients received ACE inhibitor therapy, and only 36 percent were prescribed the recommended target dose.

Thus, despite impressive evidence attesting to the efficacy of ACE inhibitor therapy in heart failure and after myocardial infarction, large numbers of patients who might otherwise benefit from these therapies remain untreated. Of particular concern, as noted in the study by Stafford and collegues,9 was the low use of ACE inhibitor therapy among diabetic patients with heart failure, a group in which treatment would not only improve the symptoms and survival from heart failure but also reduce the progression of diabetic nephropathy.11

Broader discussion of guidelines for ACE inhibitor therapy in patients with heart failure and after myocardial infarction should increase the use of these therapies. In addition, both the development of failure teams and the implementation of critical pathways for patients hospitalized with heart failure and myocardial infarction will broaden the implementation of ACE inhibitor therapy.

Deedwania has recently reviewed12 several factors that appear to limit physician use of ACE inhibitors. These factors include the following: (1) concern about hypotension, (2) the presence of coexisting renal insufficiency and (3) cough secondary to ACE inhibitor therapy. Initiating therapy at the lowest available dose and decreasing diuretics for two to three days when starting therapy is generally effective in avoiding hypotension. ACE inhibitors can usually be started safely in patients with serum creatinine levels of less than 2.5 mg per dL (220 μmol per L). They should be discontinued in patients with renal artery stenosis because significant and quick elevations in creatinine levels may occur when ACE inhibitors are prescribed in this setting. Cough has been noted to occur in as many as 20 to 30 percent of patients with heart failure during long-term therapy. Sometimes, switching to a different ACE inhibitor can effectively decrease the incidence of cough; if not, it may be necessary to consider the new angiotensin-II receptor blockers, which have been associated with a lower incidence of cough.13

In summary, the major studies and evidence to date confirm improved outcomes for patients with congestive heart failure and recent myocardial infarction who are treated with ACE inhibitor therapy. Family practitioners and cardiovascular subspecialists must become familiar with existing guidelines and implement ACE inhibitor therapy broadly for appropriate candidates. The impact of widespread use of these therapies would be a profound change in the subsequent course and outcome for millions of patients who have had a myocardial infarction and for those with congestive heart failure.

Dr. Smith is a professor of medicine and chief, Division of Cardiology at the University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, N.C. He is also director of the University of North Carolina Cardiovascular Center. He is a past president of the American Heart Association.

Address correspondence to Sidney C. Smith Jr., M.D., University of North Carolina-Chapel Hill, CB# 7075, Division of Cardiology, Chapel Hill, NC 27599-7075.

REFERENCES

1. Heart and stroke statistical update. American Heart Association, Dallas, 1997.

2. Gheorghiade M, Bonow RO. Chronic heart failure in the United States: a manifestation of coronary artery disease. Circulation. 1998;97:282–9.

3. Garg R, Yusuf S. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. Collaborative Group on ACE Inhibitor Trials [published erratum appears in JAMA. 1995;274:462]. JAMA. 1995;273:1450–6.

4. Gheorghiade M, Benatar D, Konstam MA, Stoukides CA, Bonow RO. Pharmacotherapy for systolic dysfunction: a review of randomized clinical trials [published erratum appears in Am J Cardiol. 1998;81:1521]. Am J Cardiol. 1997;80:14H–27H.

5. Antman EM, Braunwald E. Acute myocardial infarction. In: Braunwald E, ed. Heart disease: a textbook of cardiovascular medicine. 5th ed. Saunders, Philadelphia, 1997:1229.

6. Heart failure: management of patients with left ventricular systolic dysfunction. Publication no. 94-0613. Agency for Health Care Policy and Research, Rockville, Md., 1994.

7. Ryan TJ, Anderson JL, Antman EM, Braniff BA, Brooks NH, Califf RM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 1996;28:1328–1428.

8. Ellerbeck EF, Jencks SF, Radford MJ, Kresowik TF, Craig AS, Gold JA, et al. Quality of care for Medicare patients with acute myocardial infarction. A four-state pilot study from the Cooperative Cardiovascular Project. JAMA. 1995;273:1509–14.

9. Stafford RS, Saglam D, Blumenthal D. National patterns of angiotensin-converting enzyme inhibitor use in congestive heart failure. Arch Intern Med. 1997;157:2460–4.

10. Sueta CA, Petkun WM, Lulla A, Hart PL, Smith SC Jr, Simpson RJ Jr. Recommended management of hyperlipidemia and heart failure: are we following the guidelines? Circulation. 1997;96(suppl):1–66.

11. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting enzyme inhibition on diabetic nephropathy. The Collaborative Study Group [published erratum appears in N Engl J Med. 1993;330:152]. N Engl J Med. 1993;329:1456–62.

12. Deedwania PC. Underutilization of evidence-based therapy in heart failure (editorial). Arch Intern Med. 1997;157:2409–12.

13. Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I, et al. Randomized trial of losartin versus captopril in patients over 65 with heart failure. Evaluation of Losartin in the Elderly Study (ELITE). Lancet. 1997;349:747–52.


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