The role of angiotensin-converting enzyme (ACE) inhibitors has expanded beyond the original indication of hypertension. Landmark studies and practice guidelines recommend the use of ACE inhibitors in patients with heart failure, post-myocardial infarction, and post-cerebrovascular accident to decrease morbidity and mortality. However, despite a sizable amount of literature and presence in treatment guidelines, this class of medications has been traditionally underused in the primary care setting. It is for this reason that pharmacists should play a more active role in increasing appropriate ACE inhibitor usage through interventions. Second, the idea that ACE inhibitors display a “class effect” is often used to justify interchange from one particular medication to another. However, there are structural differences and pharmacokinetic nuances that should not be understated. The objective of this article is to outline uses of ACE inhibitors beyond hypertension, discuss the under use of this class despite existing literature, and touch on the idea of class effect among ACE inhibitors.
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References
1.
1. ASHP therapeutic position statement on the use of aspirin for prophylaxis of myocardial infarction. Am J Health Syst Pharm. 1997;54: 1984-1987.
2.
2. Aram V, Chobanian GL, Bakris HR, et al. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289: 2560-2571.
3.
3. Cushman WC, Ford CE, Cutler JA, et al. Success and predictors of blood pressure control in diverse North American settings: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). J Clin Hypertens. 2002;4: 393-405.
4.
4. Wing LMH, Reid CM, Ryan P, et al, for Second Australian National Blood Pressure Study Group. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med. 2003;348: 583-592.
5.
5. Luna B, Feinglos M. Drug-induced hyperglycemia. JAMA. 2001;286: 1945-1948.
6.
6. The Systolic Hypertension in the Elderly Program Cooperative Research Group. Implications of the Systolic Hypertension in the Elderly Program. Hypertension. 1993;21: 335-343
7.
7. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). American College of Cardiology Web site, 2001. Available at: http://www.acc.org/clinical/guidelines/failure/hf_index.htm.
8.
8. Bicket DP. Using ACE inhibitors appropriately. Am Fam Physician. 2002;66: 461-468.
9.
9. Johnson JA, Parker RB, Patterson JH. Heart failure. In: DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy: A Pathophysiologic Approach. 5th ed. NewYork, NY:McGraw-Hill; 2002.
10.
10. Garg R, Yusuf S, for the Collaborative Group on ACE Inhibitor Trials. Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. JAMA. 1995;273: 1450-1456.
11.
11. Yusuf S, et al, on behalf of the SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325: 293-302.
12.
12. Yusuf S, et al, on behalf of the SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med. 1992;327: 685-691.
13.
13. Packer M, Poole-Wilson PA, Armstrong PW, et al, on behalf of the ATLAS Study Group. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation. 1999;100: 2312-2318.
14.
14. Pfeffer MA, Braunwald E, Moye LA, et al, on behalf of the SAVE Investigators. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1992;327: 669-677.
15.
15. Ball SGmet al, for the Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. Lancet. 1993;342: 821-828.
16.
16. Kober L, Torp-Pedersen C, Carlsen JE, et al, for the Trandolapril Cardiac Evaluation (TRACE) Study Group. A clinical trial of the angiotensin-converting enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1995;333: 1670-1676.
17.
17. Torp-Pedersen C, Kober L, for the TRACE Study Group. Effect of ACE inhibitor trandolapril on life expectancy of patients with reduced left ventricular function after acute myocardial infarction. Lancet. 1999;354: 9-12.
18.
18. Pfeffer MA, Greaves SC, Arnold MO, et al, for the Healing and Early Afterload Reducing Therapy (HEART) Trial Investigators. Early versus delayed angiotensin-converting enzyme inhibition therapy in acute myocardial infarction. Circulation. 1997;95: 2643-2651.
19.
19. Gruppo Italiano per lo Studio della Sopravvivenza Nell’Infarto Miocardio. GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Lancet. 1994;343: 1115-1122.
20.
20. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. ISIS-4: a randomized factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulfate in 58,050 patients with suspected acute myocardial infarction. Lancet. 1995;345: 669-685.
21.
21. Swedberg K, Held P, Kjekshus J, et al, on behalf of the CONSENSUS II Study Group. Effects of early administration of enalapril on mortality in patients with acute myocardial infarction: results of the Cooperative New Scandinavian Enalapril Survival Study II (CONSENSUS II). N Engl J Med. 1992;327: 678-684.
23. Lonn EM, Yusuf S, Jha P, et al. Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection. Circulation. 1994;90: 2056-2069.
24.
[published correction appears in N Engl J Med. 1993;330: 152].
25.
25. MacMahon S, Neal B, Tzourio C, et al, on behalf of the PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6105 individuals with previous stroke or transient ischemic attack. Lancet. 2001;358: 1033-1041.
26.
26. Fagan SC, Lee LA, Hess DC. Role of angiotensin-converting enzyme inhibitors in stroke prevention. Am J Health Syst Pharm. 2003;60: 788-793.
27.
27. Schiffrin EL. Progress in secondary prevention of stroke with PROGRESS: the perindopril protection against recurrent stroke study. Curr Hypertens Rep. 2002;4: 39-40.
28.
28. Hankey GJ. Angiotensin-converting enzyme inhibitors for stroke prevention—is there HOPE for PROGRESS after LIFE? Stroke. 2003;34: 354-356.
29.
29. Yusuf S, Sleight P, Pogue J, et al, for the Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342: 145-153.
30.
30. Bosch J, Yusuf S, Pogue J, et al, on behalf of the HOPE Investigators. Use of ramipril in preventing stroke: double-blind randomized trial. BMJ. 2002;324: 1-5.
31.
31. Staessen JA, Wang J. Do ancillary properties of antihypertensive drugs explain the outcome results of recent trials? J Nephrol. 2002;15: 422-427.
32.
32. Molitch ME, DeFronzo RA, Franz MJ, et al, for the American Diabetes Association. Diabetic nephropathy—position statement. Diabetes Care. 2003;26(suppl): S94-S98.
33.
33. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317: 703-713.
34.
34. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. 1998;317: 713-720.
35.
35. Genuth S, Eastman R, Kahn R, et al, for the American Diabetes Association. Implications of the United Kingdom Prospective Diabetes Study—position statement. Diabetes Care. 2003;26(suppl): S28-S32.
36.
36. Tatti P, Pahor M, Byington RP, et al. Outcome results of the Fosinopril versus Amlodipine Cardiovascular Events Randomized Trial in patients with hypertension and NIDDM. Diabetes Care. 1998;21: 597-603.
37.
37. Hansson L, Lindholm LH, Niskanen A, et al. Effect of angiotensin-converting enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomized trial. Lancet. 1999;353: 611-616.
38.
38. Estacio RO, Jeffers BW, Hiatt WR, et al. The effect of nisoldipine as compared with enalapril on cardiovascular events in patients with non-insulin-dependent diabetes and hypertension. N Engl JMed. 1998;338: 645-652.
39.
39. Pahor M, Psaty BM, Alderman MH, et al. Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes. Diabetes Care. 2000;23: 888-892.
40.
40. Gerstein HC, Yusuf S, Mann JFE, et al, for the Heart Outcomes Prevention Evaluation (HOPE) Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000;355: 253-259.
41.
41. Chaturvedi N, Stevenson J, Fuller JH, et al, for the EUCLID Study Group. Randomized placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. Lancet. 1997;349: 1787-1792.
42.
42. Ravid M, Brosh D, Levi Z, et al. Use of enalapril to attenuate decline in renal function in normotensive normoalbuminuric patients with type 2 diabetes mellitus. Ann Intern Med. 1998;128: 982-988.
43.
43. Barron HV, Michaels AD, Maynard C, Every NR. Use of angiotensin-converting enzyme inhibitors at discharge in patients with acute myocardial infarction in the United States: data from the National Registry of Myocardial Infarction 2. J Am Coll Cardiol. 1998;32: 360-367.
44.
44. Kermani M, Dua A, Gradman AH. Underutilization and clinical benefits of angiotensin-converting enzyme inhibitors in patients with asymptomatic left ventricular dysfunction. Am J Cardiol. 2000;86: 644-648.
45.
45. Philbin EF, Weil HF, Erb TA, et al. Cardiology or primary care for heart failure in the community setting: process of care and clinical outcomes. Chest. 1999;116: 346-354.
46.
46. Reis SE, Holubkov R, Edmundowicz D, et al. Treatment of patients admitted to the hospital with congestive heart failure: specialty-related disparities in practice patterns and outcomes. J Am Coll Cardiol. 1997;30: 733-738.
47.
47. Baker DW, Hayes RP, Massie BM, et al. Variations in family physicians’ and cardiologists’ care for patients with heart failure. Am Heart J. 1999;138: 826-834.
48.
48. Bart BA, Gattis WA, Diem SJ, et al. Reasons for the under use of angiotensin-converting enzyme inhibitors in patients with heart failure and left ventricular dysfunction. Am J Cardiol. 1997;79: 1118-1120.
49.
49. Howard PA, Shireman TI, Dhingra A, et al. Patterns of ACE inhibitor use in elderly Medicaid patients with heart failure. Am J Geriatr Cardiol. 2002;11: 287-294.
50.
50. Ahmed A, Allman RM, DeLong JF, et al. Age-related underutilization of angiotensin-converting enzyme inhibitors in older hospitalized heart failure patients. South Med J. 2002;95: 703-710.
51.
51. Ahmed A, Kiefe CI, Allman RM, et al. Survival benefits of angiotensin-converting enzyme inhibitors in older heart failure patients with perceived contraindications. J Am Geriatr Soc. 2002;50: 1659-1666.
52.
52. Tu K, Mamdani MM, Jacka R, et al. The striking effect of the Heart Outcomes Prevention Evaluation (HOPE) trial on ramipril prescribing in Ontario. CMAJ. 2003;168: 553-557.
53.
53. Furberg CD. Class effects and evidence-based medicine. Clin Cardiol. 2000;23(suppl 4): 15-19.
54.
54. Ondetti MA. Structural relationships of angiotensin converting-enzyme inhibitors to pharmacological activity. Circulation. 1988;77(pt 2): 174-178.
55.
55. Zazgornik J, Kaiser W, Biesenbach G. Captopril-induced dysgeusia [letter]. Lancet. 1993;341: 1542.
56.
56. Rector TS, Johnson G, Dunkman WB, et al, for the V-HeFT VA Cooperative Studies Group. Evaluation by patients with heart failure of the effects of enalapril compared with hydralazine plus isosorbide dinitrate on quality of life: V-HeFT II. Circulation. 1993;87(suppl 6): VI71-VI77
57.
57. Hebel SK, Bernham TH, eds. Drug Facts and Comparisons. St. Louis, Mo: Facts and Comparisons Inc; 2000.
58.
58. Sica DA. Class effects of angiotensin-converting enzyme inhibitors. Am J Manag Care. 2000;6: S85-S108.
59.
59. Zannad F, Matzinger A, Larche J. Trough/peak ratios of once daily angiotensin converting enzyme inhibitors and calcium antagonists. Am J Hypertens. 1996;9: 633-643.
60.
60. The sixth report of the Joint National Committee on prevention, detection, evaluation and treatment of high blood pressure. Arch Intern Med. 1997;157: 2413-2446.
61.
61. Piepho RW. Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000;57(suppl 1): S3-S7.
62.
62. Greenwald L, Becker RC. Expanding the paradigm of the renin-angiotensin system and angiotensin-converting enzyme inhibitors. Am Heart J. 1994;128: 997-1009.
63.
63. Leonetti G, Cuspidi C. Choosing the right ACE inhibitor: a guide to selection. Drugs. 1995;49: 516-535.
64.
64. Erman A, Winkler J, Chen-Gal B, et al. Inhibition of angiotensin converting enzyme by ramipril in serum and tissue of man. J Hypertens. 1991;9: 1057-1062.
