Abstract
Hypothesis
Hypotension has been proposed as the cause of nesiritide‐associated increases in serum creatinine (SCr); however, this hypothesis has not been tested.
Methods
This retrospective evaluation of patients who had a pulmonary artery catheter and received nesiritide in the Vasodilation in the Management of Acute Congestive Heart Failure (VMAC) trial assessed hypotension, SCr elevation, concomitant therapy, and mortality. Patients were categorized by baseline pulmonary capillary wedge pressure (PCWP) and analyzed both for overall population and by diuretic dose.
Results
Compared with patients with PCWP > 23 mm Hg (n = 105), patients with PCWP ≤ 23 mm Hg (n = 49) had more hypotension within 24 hours of initiating nesiritide (16% vs 7%), but neither more SCr elevation by nominal day 30 (29% vs 28%) nor higher mortality (30 days: 8.2% vs 7.7%; 6 months: 29.0% vs 29.3%). The risk of hypotension was directly related to high dose diuretics (25% vs 6%; relative risk [RR]: 4.2; 95% confidence interval [CI]: 1.10–15.82) and was not significantly increased in patients without this concomitant treatment (10% vs 7%; RR: 1.4; 95% CI: 0.34–5.93). Additionally, high dose diuretics significantly increased the risk of SCr elevation (RR: 2.6; 95% CI: 1.03–6.64) and 6 month mortality (hazard ratio: 3.6; 95% CI: 1.19–10.63) in patients with PCWP ≤ 23 mm Hg.
Conclusions
Hypotension is not the primary etiology for nesiritide‐associated increases in SCr. High dose diuretics increase the risk of adverse outcomes in patients with PCWP ≤ 23 mm Hg and should be reserved for patients in whom PCWPs are known to be markedly elevated. Copyright © 2009 Wiley Periodicals, Inc.
Full Text
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References
- 1. Butler J, Forman DE, Abraham WT, et al. Relationship between heart failure treatment and development of worsening renal function among hospitalized patients. Am Heart J 2004; 147(2): 331–338. [DOI] [PubMed] [Google Scholar]
- 2. Forman DE, Butler J, Wang Y, et al. Incidence, predictors at admission, and impact of worsening renal function among patients hospitalized with heart failure. J Am Coll Cardiol 2004; 43(1): 61–67. [DOI] [PubMed] [Google Scholar]
- 3. Gottlieb SS, Abraham W, Butler J, et al. The prognostic importance of different definitions of worsening renal function in congestive heart failure. J Card Fail 2002; 8(3): 136–141. [DOI] [PubMed] [Google Scholar]
- 4. Krumholz HM, Chen YT, Vaccarino V, et al. Correlates and impact on outcomes of worsening renal function in patients ≥ 65 years of age with heart failure. Am J Cardiol 2000; 85(9): 1110–1113. [DOI] [PubMed] [Google Scholar]
- 5. Smith GL, Vaccarino V, Kosiborod M, et al. Worsening renal function: what is a clinically meaningful change in creatinine during hospitalization with heart failure? J Card Fail 2003; 9(1): 13–25. [DOI] [PubMed] [Google Scholar]
- 6. Sackner‐Bernstein JD, Skopicki HA, Aaronson KD Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 2005; 111(12): 1487–1491. [DOI] [PubMed] [Google Scholar]
- 7. Abraham WT Serum creatinine elevations in patients receiving nesiritide are related to starting dose. Circulation 2005; 112(17 suppl II): 589. Abstract 2789. [Google Scholar]
- 8.Publication Committee for the VMAC Investigators. Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 2002; 287(12): 1531–1540. [DOI] [PubMed] [Google Scholar]
- 9. Cheng JW, Merl MY, Nguyen HM Effect of nesiritide on renal function: a retrospective review. Curr Med Res Opin 2005; 21(11): 1857–1863. [DOI] [PubMed] [Google Scholar]
- 10. Epstein BJ Elevations in serum creatinine concentration: concerning or reassuring? Pharmacotherapy 2004; 24(5): 697–702. [DOI] [PubMed] [Google Scholar]
- 11. Bakris GL, Weir MR Angiotensin‐converting enzyme inhibitor‐associated elevations in serum creatinine: is this a cause for concern? Arch Intern Med 2000; 160(5): 685–693. [DOI] [PubMed] [Google Scholar]
- 12. Francis GS, Siegel RM, Goldsmith SR, Olivari MT, Levine TB, Cohn JN Acute vasoconstrictor response to intravenous furo‐ semide in patients with chronic congestive heart failure: activation of the neurohumoral axis. Ann Intern Med 1985; 103(1): 1–6. [DOI] [PubMed] [Google Scholar]
- 13. Francis GS, Benedict C, Johnstone DE, et al. Comparison of neuroendocrine activation in patients with left ventricular dysfunction with and without congestive heart failure: a substudy of the Studies of Left Ventricular Dysfunction (SOLVD). Circulation 1990; 82(5): 1724–1729. [DOI] [PubMed] [Google Scholar]
- 14. McCurley JM, Hanlon SU, Wei SK, Wedam EF, Michalski M, Haigney MC Furosemide and the progression of left ventricular dysfunction in experimental heart failure. J Am Coll Cardiol 2004; 44(6): 1301–1307. [DOI] [PubMed] [Google Scholar]
- 15. Knight EL, Glynn RJ, McIntyre KM, Mogun H, Avorn J Predictors of decreased renal function in patients with heart failure during angiotensin‐converting enzyme inhibitor therapy: results from the studies of left ventricular dysfunction (SOLVD). Am Heart J 1999; 138(5, pt 1): 849–855. [DOI] [PubMed] [Google Scholar]
- 16. Gottlieb SS, Brater DC, Thomas I, et al. BG9719 (CVT‐124), an A1 adenosine receptor antagonist, protects against the decline in renal function observed with diuretic therapy. Circulation 2002; 105(11): 1348–1353. [DOI] [PubMed] [Google Scholar]
- 17. Neuberg GW, Miller AB, O'Connor CM, et al. Diuretic resistance predicts mortality in patients with advanced heart failure. Am Heart J 2002; 144(1): 31–38. [DOI] [PubMed] [Google Scholar]
- 18. Domanski M, Norman J, Pitt B Diuretic use, progressive heart failure, and death in patients in the Studies Of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol 2003; 42(4): 705–708. [DOI] [PubMed] [Google Scholar]
- 19. Emerman CL, DeMarco T, Costanzo MR, Peacock WR Impact of intravenous diuretics on the outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. J Card Fail 2004; 10(4suppl1): S116–S117. Abstract 368. [DOI] [PubMed] [Google Scholar]
- 20. Eshaghian S, Horwich TB, Fonarow GC Relation of loop diuretic dose to mortality in advanced heart failure. Am J Cardiol 2006; 97(12): 1759–1764. [DOI] [PubMed] [Google Scholar]
- 21. Domanski M, Tian X, Haigney M, Pitt B Diuretic use, progressive heart failure, and death in patients in the DIG study. J Card Fail 2006; 12(5): 327–332. [DOI] [PubMed] [Google Scholar]
- 22. Hasselblad V, Gattis Stough W, Shah MR, et al. Relation between dose of loop diuretics and outcomes in a heart failure population: results of the ESCAPE trial. Eur J Heart Fail 2007; 9(10): 1064–1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. Ishii J, Nomura M, Nakamura Y, et al. Risk stratification using a combination of cardiac troponin T and brain natriuretic peptide in patients hospitalized for worsening chronic heart failure. Am J Cardiol 2002; 89(6): 691–695. [DOI] [PubMed] [Google Scholar]
- 24. Ahmed A, Aronow WS, Fleg JL Higher New York Heart Association classes and increased mortality and hospitalization in patients with heart failure and preserved left ventricular function. Am Heart J 2006; 151(2): 444–450. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Binanay C, Califf RM, Hasselblad V, et al. Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness: the ESCAPE trial. JAMA 2005; 294(13): 1625–1633. [DOI] [PubMed] [Google Scholar]