ACE Inhibitors for Older Patients with Heart Failure: A Review of Evidence, Practice Patterns and ChallengesPeterson P.N.a · Masoudi F.A.a, b
aDepartment of Medicine, Division of Cardiology, University of Colorado Health Sciences Center, and bDepartment of Medicine, Division of Cardiology, Denver Health Medical Center, Denver, Colo., USA
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Article / Publication Details
Heart failure is predominantly a condition of the elderly and is associated with substantial mortality, morbidity and functional limitation. In clinical trials of patients with left ventricular systolic dysfunction (LVSD), angiotensin-converting enzyme (ACE) inhibitors reduce the burden of heart failure. Clinical trials, however, have largely excluded older persons. This paper reviews the evidence for efficacy and effectiveness of ACE inhibitors, current patterns of use of these important agents and the challenges of prescribing ACE inhibitors for older patients with heart failure. The existing literature indicates that (1) despite a relative paucity of data from randomized controlled trials, observational studies suggest that the elderly with LVSD are as likely to benefit from ACE inhibitors as younger patients; (2) ACE inhibitors are underused in older persons despite guideline recommendations, and (3) the older population presents specific challenges in applying the clinical evidence supporting ACE inhibitors, including polypharmacy, cognitive impairment and other common comorbid conditions. Nevertheless, the judicious use of ACE inhibitors in eligible older patients will likely improve health outcomes.
© 2005 S. Karger AG, Basel
- Rich MW: Epidemiology, pathophysiology, and etiology of congestive heart failure in older adults. J Am Geriatr Soc 1997;45:968–974.
- Havranek EP, Masoudi FA, Westfall KA, Wolfe P, Ordin DL, Krumholz HM: Spectrum of heart failure in older patients: Results from the National Heart Failure project. Am Heart J 2002;143:412–417.
- Havranek EP, Abrams F, Stevens E, Parker K: Determinants of mortality in elderly patients with heart failure: The role of angiotensin-converting enzyme inhibitors. Arch Intern Med 1998;158:2024–2028.
- Senni M, Tribouilloy CM, Rodeheffer RJ, Jacobsen SJ, Evans JM, Bailey KR, et al: Congestive heart failure in the community: A study of all incident cases in Olmsted County, Minnesota, in 1991. Circulation 1998;98:2282–2289.
- MacIntyre K, Capewell S, Stewart S, Chalmers JW, Boyd J, Finlayson A, et al: Evidence of improving prognosis in heart failure: Trends in case fatality in 66 547 patients hospitalized between 1986 and 1995. Circulation 2000;102:1126–1131.
- Foot DK, Lewis RP, Pearson TA, Beller GA: Demographics and cardiology, 1950–2050. J Am Coll Cardiol 2000;35:66B–80B.
US Census: www census gov/ipc/www/usinterimproj/natrojtab02a pdf.
- Roger VL, Weston SA, Redfield MM, Hellermann-Homan JP, Killian J, Yawn BP, et al: Trends in heart failure incidence and survival in a community-based population. JAMA 2004;292:344–350.
- McCullough PA, Philbin EF, Spertus JA, Kaatz S, Sandberg KR, Weaver WD: Confirmation of a heart failure epidemic: Findings from the Resource Utilization Among Congestive Heart Failure (REACH) study. J Am Coll Cardiol 2002;39:60–69.
- Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D: Survival after the onset of congestive heart failure in Framingham Heart Study subjects. Circulation 1993;88:107–115.
- Pulignano G, Del SD, Tavazzi L, Lucci D, Gorini M, Leggio F, et al: Clinical features and outcomes of elderly outpatients with heart failure followed up in hospital cardiology units: Data from a large nationwide cardiology database (IN-CHF Registry). Am Heart J 2002;143:45–55.
- Croft JB, Giles WH, Pollard RA, Keenan NL, Casper ML, Anda RF: Heart failure survival among older adults in the United States: A poor prognosis for an emerging epidemic in the Medicare population. Arch Intern Med 1999;159:505–510.
- Rathore SS, Foody JM, Wang Y, Smith GL, Herrin J, Masoudi FA, et al: Race, quality of care, and outcomes of elderly patients hospitalized with heart failure. JAMA 2003;289:2517–2524.
Graves EG: 1993 Summary: National Hospital Discharge Survey. Advance Data from Vital and Health Statistics. Hyattsville, National Center for Health Statistics, 1995.
Hall MJ, DeFrances CJ: 2001 National Hospital Discharge Survey. Advance Data from Vital and Health Statistics. Hyattsville, National Center for Health Statistics, 2003.
- Krumholz HM, Parent EM, Tu N, Vaccarino V, Wang Y, Radford MJ, et al: Readmission after hospitalization for congestive heart failure among Medicare beneficiaries. Arch Intern Med 1997;157:99–104.
- Vinson JM, Rich MW, Sperry JC, Shah AS, McNamara T: Early readmission of elderly patients with congestive heart failure. J Am Geriatr Soc 1990;38:1290–1295.
- Van Jaarsveld CH, Sanderman R, Miedema I, Ranchor AV, Kempen GI: Changes in health-related quality of life in older patients with acute myocardial infarction or congestive heart failure: A prospective study. J Am Geriatr Soc 2001;49:1052–1058.
- Juenger J, Schellberg D, Kraemer S, Haunstetter A, Zugck C, Herzog W, et al: Health related quality of life in patients with congestive heart failure: Comparison with other chronic diseases and relation to functional variables. Heart 2002;87:235–241.
- Masoudi FA, Rumsfeld JS, Havranek EP, House JA, Peterson ED, Krumholz HM, et al: Age, functional capacity, and health-related quality of life in patients with heart failure. J Cardiac Fail 2004;10:368–373.
- The CONSENSUS Trial Study Group: Effects of enalapril on mortality in severe congestive heart failure. Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med 1987;316:1429–1435.
- 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.
- 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.
- Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, et al: Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med 1992;327:669–677.
- Kober L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K, et al: A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med 1995;333:1670–1676.
- Effect of ramipril on mortality and morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure. The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators. Lancet 1993;342:821–828.
- Flather MD, Yusuf S, Kober L, Pfeffer M, Hall A, Murray G, et al: Long-term ACE-inhibitor therapy in patients with heart failure or left-ventricular dysfunction: A systematic overview of data from individual patients. ACE-Inhibitor Myocardial Infarction Collaborative Group. Lancet 2000;355:1575–1581.
- 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. JAMA 1995;273:1450–1456.
- Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, et al: ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult. Circulation 2001;104:2996–3007.
- Remme WJ, Swedberg K, Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology: Guidelines for the diagnosis and treatment of chronic heart failure. Eur Heart J 2001;22:1527–1560.
- Gottdiener JS, McClelland RL, Marshall R, Shemanski L, Furberg CD, Kitzman DW, et al: Outcome of congestive heart failure in elderly persons: Influence of left ventricular systolic function. The Cardiovascular Health Study. Ann Intern Med 2002;137:631–639.
- Masoudi FA, Rathore SS, Wang Y, Havranek EP, Curtis JP, Foody JM, et al: National patterns of use and effectiveness of angiotensin-converting enzyme inhibitors in older patients with heart failure and left ventricular systolic dysfunction. Circulation 2004;110:724–731.
- Masoudi FA, Havranek EP, Wolfe P, Gross CP, Rathore SS, Steiner JF, et al: Most hospitalized older persons do not meet the enrollment criteria for clinical trials in heart failure. Am Heart J 2003;146:250–257.
- Philbin EF, Andreaou C, Rocco TA, Lynch LJ, Baker SL: Patterns of angiotensin-converting enzyme inhibitor use in congestive heart failure in two community hospitals. Am J Cardiol 1996;77:832–838.
- Johnson D, Jin Y, Quan H, Cujec B: Beta-blockers and angiotensin-converting enzyme inhibitors/receptor blockers prescriptions after hospital discharge for heart failure are associated with decreased mortality in Alberta, Canada. J Am Coll Cardiol 2003;42:1438–1445.
- Smith NL, Psaty BM, Pitt B, Garg R, Gottdiener JS, Heckbert SR: Temporal patterns in the medical treatment of congestive heart failure with angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995. Arch Intern Med 1998;158:1074–1080.
- Stafford RS, Radley DC: The underutilization of cardiac medications of proven benefit, 1990 to 2002. J Am Coll Cardiol 2003;41:56–61.
- 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.
Mortality risk and patterns of practice in 4606 acute care patients with congestive heart failure. The relative importance of age, sex, and medical therapy. Clinical Quality Improvement Network Investigators. Arch Intern Med 1996;156:1669–1673.
- Jencks SF, Huff ED, Cuerdon T: Change in the quality of care delivered to Medicare beneficiaries, 1998–1999 to 2000–2001. JAMA 2003;289:305–312.
- Butler J, Arbogast PG, Daugherty J, Jain MK, Ray WA, Griffin MR: Outpatient utilization of angiotensin-converting enzyme inhibitors among heart failure patients after hospital discharge. J Am Coll Cardiol 2004;43:2036–2043.
- Senni M, Rodeheffer RJ, Tribouilloy CM, Evans JM, Jacobsen SJ, Bailey KR, et al: Use of echocardiography in the management of congestive heart failure in the community. J Am Coll Cardiol 1999;33:164–170.
- Ahmed A, Kiefe CI, Allman RM, Sims RV, DeLong JF: Survival benefits of angiotensin-converting enzyme inhibitors in older heart failure patients with perceived contraindications. J Am Geriatr Soc 2002;50:1659–1666.
- Philbin EF, Santella RN, Rocco TA Jr: Angiotensin-converting enzyme inhibitor use in older patients with heart failure and renal dysfunction. J Am Geriatr Soc 1999;47:302–308.
- Edep ME, Shah NB, Tateo IM, Massie BM: Differences between primary care physicians and cardiologists in management of congestive heart failure: Relation to practice guidelines. J Am Coll Cardiol 1997;30:518–526.
- Houghton AR, Cowley AJ: Why are angiotensin converting enzyme inhibitors underutilised in the treatment of heart failure by general practitioners? Int J Cardiol 1997;59:7–10.
- Philbin EF, Weil HF, Erb TA, Jenkins PL: Cardiology or primary care for heart failure in the community setting: Process of care and clinical outcomes. Chest 1999;116:346–354.
- Parmley WW: Do we practice geriatric cardiology? J Am Coll Cardiol 1997;29:217–218.
- Foody JM, Rathore SS, Wang Y, Herrin J, Masoudi FA, Havranek EP, et al: Predictors of cardiologist care for older patients hospitalized for heart failure. Am Heart J 2004;147:66–73.
- Krumholz HM, Amatruda J, Smith GL, Mattera JA, Roumanis SA, Radford MJ, et al: Randomized trial of an education and support intervention to prevent readmission of patients with heart failure. J Am Coll Cardiol 2002;39:83–89.
- Rich MW, Beckham V, Wittenberg C, Leven CL, Freedland KE, Carney RM: A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure. N Engl J Med 1995;333:1190–1195.
- Philbin EF: Comprehensive multidisciplinary programs for the management of patients with congestive heart failure. J Gen Intern Med 1999;14:130–135.
- Uretsky BF, Shaver JA, Liang CS, Amin D, Shah PK, Levine TB, et al: Modulation of hemodynamic effects with a converting enzyme inhibitor: Acute hemodynamic dose-response relationship of a new angiotensin converting enzyme inhibitor, lisinopril, with observations on long-term clinical, functional, and biochemical responses. Am Heart J 1988;116:480–488.
- Pacher R, Globits S, Bergler-Klein J, Teufelsbauer H, Wutte M, Baumgartner W, et al: Clinical and neurohumoral response of patients with severe congestive heart failure treated with two different captopril dosages. Eur Heart J 1993;14:273–278.
- Clinical outcome with enalapril in symptomatic chronic heart failure; a dose comparison. The NETWORK Investigators. Eur Heart J 1998;19:481–489.
- Packer M, Poole-Wilson PA, Armstrong PW, Cleland JG, Horowitz JD, Massie BM, et al: Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. ATLAS Study Group. Circulation 1999;100:2312–2318.
- Chen YT, Wang Y, Radford MJ, Krumholz HM: Angiotensin-converting enzyme inhibitor dosages in elderly patients with heart failure. Am Heart J 2001;141:410–417.
- Rochon PA, Sykora K, Bronskill SE, Mamdani M, Anderson GM, Gurwitz JH, et al: Use of angiotensin-converting enzyme inhibitor therapy and dose-related outcomes in older adults with new heart failure in the community. J Gen Intern Med 2004;19:676–683.
- Manyemba J, Mangoni AA, Pettingale KW, Jackson SH: Determinants of failure to prescribe target doses of angiotensin-converting enzyme inhibitors for heart failure. Eur J Heart Fail 2003;5:693–696.
- Forman DE, Chander RB, Lapane KL, Shah P, Stoukides J: Evaluating the use of angiotensin-converting enzyme inhibitors for older nursing home residents with chronic heart failure. J Am Geriatr Soc 1998;46:1550–1554.
- Lien CT, Gillespie ND, Struthers AD, McMurdo ME: Heart failure in frail elderly patients: Diagnostic difficulties, co-morbidities, polypharmacy and treatment dilemmas. Eur J Heart Fail 2002;4:91–98.
- Gurwitz JH, Field TS, Harrold LR, Rothschild J, Debellis K, Seger AC, et al: Incidence and preventability of adverse drug events among older persons in the ambulatory setting. JAMA 2003;289:1107–1116.
- Schroeder K, Fahey T, Ebrahim S: How can we improve adherence to blood pressure-lowering medications in ambulatory care? Systematic review of randomized controlled trials. Arch Intern Med 2004;164:722–732.
- Gambassi G, Forman DE, Lapane KL, Mor V, Sgadari A, Lipsitz LA, et al: Management of heart failure among very old persons living in long-term care: Has the voice of trials spread? The SAGE Study Group. Am Heart J 2000;139:85–93.
- Sloss EM, Solomon DH, Shekelle PG, Young RT, Saliba D, MacLean CH, et al: Selecting target conditions for quality of care improvement in vulnerable older adults. J Am Geriatr Soc 2000;48:363–369.
- Fahey T, Montgomery AA, Barnes J, Protheroe J: Quality of care for elderly residents in nursing homes and elderly people living at home: Controlled observational study. BMJ 2003;326:580.
- Higashi T, Shekelle PG, Solomon DH, Knight EL, Roth C, Chang JT, et al: The quality of pharmacologic care for vulnerable older patients. Ann Intern Med 2004;140:714–720.
- Amabile CM, Spencer AP: Keeping your patient with heart failure safe: A review of potentially dangerous medications. Arch Intern Med 2004;164:709–720.
- Krumholz HM, Chen YT, Vaccarino V, Wang Y, Radford MJ, Bradford WD, et al: Correlates and impact on outcomes of worsening renal function in patients > or = 65 years of age with heart failure. Am J Cardiol 2000;85:1110–1113.
- Butler J, Forman DE, Abraham WT, Gottlieb SS, Loh E, Massie BM, et al: Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J 2004;147:331–338.
- Ljungman S, Kjekshus J, Swedberg K: Renal function in severe congestive heart failure during treatment with enalapril [the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) Trial]. Am J Cardiol 1992;70:479–487.
- Bakris GL, Weir MR: Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: Is this a cause for concern? Arch Intern Med 2000;160:685–693.
- Swedko PJ, Clark HD, Paramsothy K, Akbari A: Serum creatinine is an inadequate screening test for renal failure in elderly patients. Arch Intern Med 2003;163:356–360.
- McAlister FA, Ezekowitz J, Tonelli M, Armstrong PW: Renal insufficiency and heart failure: Prognostic and therapeutic implications from a prospective cohort study. Circulation 2004;109:1004–1009.
- Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW: The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol 2000;35:681–689.
- Bart BA, Ertl G, Held P, Kuch J, Maggioni AP, McMurray J, et al: Contemporary management of patients with left ventricular systolic dysfunction. Results from the Study of Patients Intolerant of Converting Enzyme Inhibitors (SPICE) Registry. Eur Heart J 1999;1182–1190.
- Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, et al: Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function intolerant to angiotensin-converting-enzyme inhibitors: The CHARM-Alternative trial. Lancet 2003;362:772–776.
- Morimoto T, Gandhi TK, Fiskio JM, Seger AC, So JW, Cook EF, et al: Development and validation of a clinical prediction rule for angiotensin-converting enzyme inhibitor-induced cough. J Gen Intern Med 2004;19:684–691.
- Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, et al: Effects of candesartan on mortality and morbidity in patients with chronic heart failure: The CHARM-Overall programme. Lancet 2003;362:759–766.
- Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I, et al: Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997;349:747–752.
- Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, et al: Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: Randomised trial – The Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582–1587.
- Pfeffer MA, McMurray JJ, Velazquez EJ, Rouleau JL, Kober L, Maggioni AP, et al: Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med 2003;349:1893–1906.
- Antman EM, Anbe DT, Armstrong PW, Bates ER, Green LA, Hand M, et al: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction – Executive summary. Circulation 2004;110:588–636.
- Wolinsky FD, Overhage JM, Stump TE, Lubitz RM, Smith DM: The risk of hospitalization for congestive heart failure among older adults. Med Care 1997;35:1031–1043.
- Masoudi FA, Havranek EP, Smith G, Fish RH, Steiner JF, Ordin DL, et al: Gender, age, and heart failure with preserved left ventricular systolic function. J Am Coll Cardiol 2003;41:217–223.
- Hogg K, Swedberg K, McMurray J: Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol 2004;43:317–327.
- Lenzen MJ, Scholte op Reimer WJ, Boersma E, Vantrimpont PJ, Follath F, Swedberg K, et al: Differences between patients with a preserved and a depressed left ventricular function: A report from the Euro Heart Failure Survey. Eur Heart J 2004;25:1214–1220.
- Smith GL, Masoudi FA, Vaccarino V, Radford MJ, Krumholz HM: Outcomes in heart failure patients with preserved ejection fraction. Mortality, readmission, and functional decline. J Am Coll Cardiol 2003;41:1510–1518.
- Philbin EF, TA Jr: Use of angiotensin-converting enzyme inhibitors in heart failure with preserved left ventricular systolic function. Am Heart J 1997;134:188–195.
- Aronow WS and Kronzon I: Effect of enalapril on congestive heart failure treated with diuretics in elderly patients with prior myocardial infarction and normal left ventricular ejection fraction. Am J Cardiol 1993;71:602–604.
- Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, et al: Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: The CHARM-Preserved trial. Lancet 2003;362:777–781.
- Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G: Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:145–153.
- Fox KM: Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: Randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study). Lancet 2003;362:782–788.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.