Objectives: Patients with heart failure (HF) and reduced left-ventricular ejection fraction (LVEF) benefit from angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blocker (ARB) therapy. While dose reduction/discontinuation (r/d) of β-blockers (BB) and furosemide in acute decompensated HF (ADHF) worsen outcomes, data on ACEI/ARB are lacking. Methods: To determine the frequency and reasons for ACEI/ARB therapy r/d in ADHF patients, we studied 174 patients with LVEF <40% on ACEI/ARB and BB therapy upon admission over 1 year. Results: ACEI/ARB doses were r/d in 17.2% because of acute kidney injury (56.7%), hypotension (23.3%), and hyperkalemia (10%). Clinical characteristics were similar between patients with r/d and continued therapy. Admission and discharge creatinine (Cr) levels were higher in the r/d group. On multivariate analysis, admission Cr and admission systolic blood pressures were independent predictors of r/d. Among patients with renal dysfunction cited as the r/d reason, Cr did not significantly rise in 23.5%. The r/d group had a longer length of stay (LOS). Conclusions: ACEI/ARB dose is reduced and/or discontinued in nearly one-fifth of all ADHF admissions, and LOS is longer in the ACEI/ARB r/d group. While impaired renal function is the most frequently cited reason, nearly one-fourth of the patients had stable renal function. ACEI/ARB r/d therapy in the setting of ADHF merits further study.

Journal Section:
Editor's choice
Keywords:
Angiotensin-converting enzyme inhibitors, Angiotensin receptor blockers, Congestive heart failure
1.
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.
[PubMed]
https://doi.org/10.1056/NEJM198706043162301
2.
Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The SOLVD Investigators. N Engl J Med 1991;325:293-302.
[PubMed]
https://doi.org/10.1056/NEJM199108013250501
3.
Swedberg K, Kjekshus J, Snapinn S: Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I. Eur Heart J 1999;20:136-139.
[PubMed]
https://doi.org/10.1053/euhj.1998.1098
4.
Granger CB, McMurray JJ, Yusuf S, Held P, Michelson EL, Olofsson B, Ostergren J, Pfeffer MA, Swedberg K: 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.
[PubMed]
https://doi.org/10.1016/S0140-6736(03)14284-5
5.
Ross JS, Chen J, Lin Z, Bueno H, Curtis JP, Keenan PS, Normand SL, Schreiner G, Spertus JA, Vidán MT, Wang Y, Wang Y, Krumholz HM: Recent national trends in readmission rates after heart failure hospitalization. Circ Heart Fail 2010;3:97-103.
[PubMed]
https://doi.org/10.1161/CIRCHEARTFAILURE.109.885210
6.
Prins KW, Neill JM, Tyler JO, Eckman PM, Duval S: Effects of beta-blocker withdrawal in acute decompensated heart failure: a systematic review and meta-analysis. JACC Heart Fail 2015;8:647-653.
[PubMed]
https://doi.org/10.1016/j.jchf.2015.03.008
7.
Woodruff AE, Kelley AM, Hempel CA, Loeffler WJ, Echtenkamp CA, Hassan AK: Discharge diuretic dose and 30 day readmission rate in acute decompensated heart failure. Ann Pharmacother 2016;50:437-445.
[PubMed]
https://doi.org/10.1177/1060028016637385
8.
Tsai JP, Rochon PA, Raptis S, Bronskill SE, Bell CM, Saposnik G: A prescription at discharge improves long-term adherence for secondary stroke prevention. J Stroke Cerebrovasc Dis 2014;23:2308-2315.
[PubMed]
https://doi.org/10.1016/j.jstrokecerebrovasdis.2014.04.026
9.
Ivers NM, Schwalm JD, Jackevicius CA, Guo H, Tu JV, Natarajan M: Length of initial prescription at hospitalization and long-term medication adherence in elderly patients with coronary artery disease: a population level study. Can J Cardiol 2013;29:1408-1414.
[PubMed]
https://doi.org/10.1016/j.cjca.2013.04.009
10.
Ahmed A, Centor RM, Weaver MT, Perry GJ: A propensity score analysis of the impact of angiotensin-converting enzyme inhibitors on long-term survival of older adults with heart failure and perceived contraindications. Am Heart J 2005;149:737-743.
[PubMed]
https://doi.org/10.1016/j.ahj.2004.06.030
11.
Palevsky PM, Liu KD, Brophy PD, Chawla LS, Parikh CR, Thakar CV, Tolwani AJ, Waikar SS, Weisbord SD: KDOQI US commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury. Am J Kidney Dis 2013;61:649-672.
[PubMed]
https://doi.org/10.1053/j.ajkd.2013.02.349
12.
Heywood JT, Fonarow GC, Costanzo MR, Mathur VS, Wigneswaran JR, Wynne J, ADHERE Scientific Advisory Committee and Investigators: High prevalence of renal dysfunction and its impact on outcome in 118,465 patients hospitalized with acute decompensated heart failure: a report from the ADHERE database. J Card Fail 2007;13:422-430.
[PubMed]
https://doi.org/10.1016/j.cardfail.2007.03.011
13.
Smith GL, Lichtman JH, Bracken MB, Shlipak MG, Phillips CO, DiCapua P, Krumholz HM: Renal impairment and outcomes in heart failure: systemic review and meta-analysis. J Am Coll Cardiol 2006;47:1987-1996.
[PubMed]
https://doi.org/10.1016/j.jacc.2005.11.084
14.
Roy AK, Mc Gorrian C, Treacy C, Kavanaugh E, Brennan A, Mahon NG, Murray PT: A comparison of traditional and novel definitions (RIFLE, AKIN, and KDIGO) of acute kidney injury for the prediction of outcomes in acute decompensated heart failure. Cardiorenal Med 2013;3:26-37.
[PubMed]
https://doi.org/10.1159/000347037
15.
Ahmed A, Fonarow GC, Zhang Y, Sanders PW, Allman RM, Arnett DK, Feller MA, Love TE, Aban IB, Levesque R, Ekundayo OJ, Dell'Italia LJ, Bakris GL, Rich MW: Renin-angiotensin inhibition in systolic heart failure and chronic kidney disease. Am J Med 2012;125:399-410.
[PubMed]
https://doi.org/10.1016/j.amjmed.2011.10.013
16.
Berra G, Garin N, Stirnemann J, Jannot AS, Martin PY, Perrier A, Carballo S: Outcome in acute heart failure: prognostic value of acute kidney injury and worsening renal function. J Card Fail 2015;5:382-390.
[PubMed]
https://doi.org/10.1016/j.cardfail.2014.12.015
17.
Sheerin NJ, Newton PJ, Macdonald PS, Leung DY, Sibbritt D, Spicer ST, Johnson K, Krum H, Davidson PM: Worsening renal function in heart failure: the need for a consensus definition. Int J Cardiol 2014;174:484-491.
[PubMed]
https://doi.org/10.1016/j.ijcard.2014.04.162
18.
Rouleau JL, Roecker EB, Tendera M, Mohacsi P, Krum H, Katus HA, Fowler MB, Coats AJ, Castaigne A, Scherhag A, Holcslaw TL, Packer M: Carvedilol Prospective Randomized Cumulative Survival Study Group. Influence of pretreatment systolic blood pressure on the effect of carvedilol in patients with severe chronic heart failure: the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) study. J Am Coll Cardiol 2004;43:1423-1429.
[PubMed]
https://doi.org/10.1016/j.jacc.2003.11.037
19.
Garg R, Yusuf S: Overview of randomized trials of angiotensin-converting enzyme inhibitors on mortality and morbidity in patients with heart failure. JAMA 1995;273:1450-1456.
[PubMed]
https://doi.org/10.1001/jama.1995.03520420066040
20.
Exner DV, Dries DL, Domanski MJ, Cohn JN: Lesser response to angiotensin-converting-enzyme inhibitor therapy in black as compared with white patients with left ventricular dysfunction. N Engl J Med 2001;344:1351-1357.
[PubMed]
https://doi.org/10.1056/NEJM200105033441802
21.
El-Refai M, Hrobowski T, Peterson EL, Wells K, Spertus JA, Williams LK, Lanfear DE: Race and association of angiotensin converting enzyme/angiotensin receptor blocker exposure with outcome in heart failure. J Cardiovasc Med (Hagerstown) 2015;16:591-596.
[PubMed]
https://doi.org/10.2459/JCM.0000000000000091
22.
Writing Committee Members, Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013;128:e240-e327.
[PubMed]
https://doi.org/10.1161/CIR.0b013e31829e8776
23.
Gordin JS, Fonarow GC: New medications in heart failure. Trends Cardiovasc Med 2016;26:485-492.
[PubMed]
https://doi.org/10.1016/j.tcm.2016.02.008
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