Skip to main content
SpringerLink
Log in

Nonsteroidal Anti-Inflammatory Drugs and Heart Failure

  • Current Opinion
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Heart failure constitutes an increasing public health problem because of the growing incidence and prevalence, poor prognosis and high hospital (re)admission rates. Myocardial infarction is the underlying cause in the majority of patients, followed by hypertension, valvular heart disease and idiopathic cardio-myopathy.

Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit the enzymes cyclo-oxygenase (COX) 1 and 2, have been associated with the occurrence of symptoms of heart failure in several case reports and quantitative studies, mainly in patients with a history of cardiovascular disease or left ventricular impairment. NSAIDs may impair renal function in patients with a decreased effective circulating volume by inhibiting prostaglandin synthesis. Consequently, water and sodium retention, and decreases in renal blood flow and glomerular filtration rate may occur, affecting the unstable cardiovascular homeostasis in these patients. In patients with pre-existing heart failure, this may lead to cardiac decompensation. Putative renal-sparing NSAIDs, such as COX-2 selective inhibitors have similar effects on renal function as the traditional NSAIDs, and can likewise be expected to increase the risk of heart failure in susceptible patients. NSAIDs are frequently prescribed to elderly patients, who are particularly at risk for the renal adverse effects. If treatment with NSAIDs in high risk patients cannot be avoided, intensive monitoring and patient education is important.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Table I

Similar content being viewed by others

References

  1. McMurray JJ, Stewart S. Epidemiology, aetiology, and prognosis of heart failure. Heart 2000 May; 83(5): 596–602

    Article  PubMed  CAS  Google Scholar 

  2. Kannel WB, Belanger AJ. Epidemiology of heart failure. Am Heart J 1991 Mar; 121 (3 Pt 1): 951–7

    Article  PubMed  CAS  Google Scholar 

  3. Ho KK, Pinsky JL, Kannel WB, et al. The epidemiology of heart failure: the Framingham Study. J Am Coll Cardiol 1993 Oct; 22 (4 Suppl A): 6A–13A

    Article  PubMed  CAS  Google Scholar 

  4. Mosterd A, Cost B, Hoes AW, et al. The prognosis of heart failure in the general population: the Rotterdam Study. Eur Heart J 2001 Aug; 22(15): 1318–27

    Article  PubMed  CAS  Google Scholar 

  5. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. 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) J Am Coll Cardiol 2001 Dec; 38(7): 2101–13

    Article  PubMed  CAS  Google Scholar 

  6. Remme WJ, Swedberg K. Guidelines for the diagnosis and treatment of chronic heart failure. Task Force for the diagnosis and treatment of chronic heart failure, European Society of Cardiology. Eur Heart J 2001 Sep; 22(17): 1527–60

    Article  PubMed  CAS  Google Scholar 

  7. Packer M. Pathophysiology of chronic heart failure. Lancet 1992 Jul 11; 340(8811): 88–92

    Article  PubMed  CAS  Google Scholar 

  8. Feenstra J, Grobbee DE, Remme WJ, et al. Drug-induced heart failure. J Am Coll Cardiol 1999 Apr; 33(5): 1152–62

    Article  PubMed  CAS  Google Scholar 

  9. Tashima CK, Rose M. Pulmonary edema and salicylates [letter]. Ann Intern Med 1974 Aug; 81(2): 274–5

    PubMed  CAS  Google Scholar 

  10. Schooley RT, Wagley PF, Lietman PS. Edema associated with ibuprofen therapy. JAMA 1977 Apr 18; 237(16): 1716–7

    Article  PubMed  CAS  Google Scholar 

  11. Nevins M, Berque S, Corwin N, et al. Phenylbutazone and pulmonary oedema. Lancet 1969 Dec 20; 2(7634): 1358

    Article  PubMed  CAS  Google Scholar 

  12. Van den Ouweland FA, Gribnau FW, Meyboom RH. Congestive heart failure due to nonsteroidal anti-inflammatory drugs in the elderly. Age Ageing 1988 Jan; 17(1): 8–16

    Article  PubMed  Google Scholar 

  13. Feenstra J, Stricker BHC. Heart failure and fluid retention attributed to the use of non-steroidal anti-inflammatory drugs [in Dutch]. Ned Tijdschr Geneeskd 1996 Oct 5; 140(40): 2000–3

    PubMed  CAS  Google Scholar 

  14. Brooks P. Use and benefits of nonsteroidal anti-inflammatory drugs. Am J Med 1998 Mar 30; 104(3A): 9S–13S

    Article  PubMed  CAS  Google Scholar 

  15. Tamblyn R, Berkson L, Dauphinee WD, et al. Unnecessary prescribing of NSAIDs and the management of NSAID-related gastropathy in medical practice. Ann Intern Med 1997 Sep 15; 127(6): 429–38

    PubMed  CAS  Google Scholar 

  16. Brater DC, Harris C, Redfern JS, et al. Renal effects of COX-2-selective inhibitors. Am J Nephrol 2001 Jan–Feb; 21(1): 1–15

    Article  PubMed  CAS  Google Scholar 

  17. Bennett WM, Henrich WL, Stoff JS. The renal effects of nonsteroidal anti-inflammatory drugs: summary and recommendations. Am J Kidney Dis 1996 Jul; 28 (1 Suppl. 1): S56–62

    Article  PubMed  CAS  Google Scholar 

  18. Feenstra J, Grobbee DE, Mosterd A, et al. Adverse cardiovascular effects of NSAIDs in patients with congestive heart failure. Drug Saf 1997 Sep; 17(3): 166–80

    Article  PubMed  CAS  Google Scholar 

  19. Hirsch AT, Dzau VJ, Creager A. Broreceptor function in congestive heart failure: effect on neurohormonal activation and regional vascular resistance. Circulation 1987 May; 75 (5 Pt 2): IV36–48

    PubMed  CAS  Google Scholar 

  20. Baughman KL. B-type natriuretic peptide-a window to the heart. N Engl J Med 2002 Jul 18; 347(3): 158–9

    Article  PubMed  Google Scholar 

  21. Packer M. Interaction of prostaglandins and angiotensin II in the modulation of renal function in congestive heart failure. Circulation 1988 Jun; 77 (6 Pt 2): 164–73

    Article  Google Scholar 

  22. Davies NM, Skjodt NM. Choosing the right nonsteroidal anti-inflammatory drug for the right patient. Clin Pharmacokinet 2000 May; 38(5): 377–92

    Article  PubMed  CAS  Google Scholar 

  23. Simon LS, Mills JA. Drug therapy: nonsteroidal antiinflam-matory drugs (first of two parts). N Engl J Med 1980 May 22; 302(21): 1179–85

    Article  PubMed  CAS  Google Scholar 

  24. Meade EA, Smith WL, DeWitt DL. Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. J Biol Chem 1993 Mar 25; 268(9): 6610–4

    PubMed  CAS  Google Scholar 

  25. Schlondorff D. Renal complications of nonsteroidal anti-inflammatory drugs. Kidney Int 1993 Sep; 44(3): 643–53

    Article  PubMed  CAS  Google Scholar 

  26. Carmichael J, Shankel SW. Effects of nonsteroidal anti-inflammatory drugs on prostaglandins and renal function. Am J Med 1985 Jun; 78 (6 Pt 1): 992–1000

    Article  PubMed  CAS  Google Scholar 

  27. Whelton A. Renal aspects of treatment with conventional nonsteroidal anti-inflammatory drugs versus cyclooxygenase-2-specific inhibitors. Am J Med 2001 Feb 19; 110 (Suppl 3A): 33S–42S

    Article  PubMed  CAS  Google Scholar 

  28. Clive DM, Stoff JS. Renal syndromes associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1984 Mar 1; 310(9): 563–72

    Article  PubMed  CAS  Google Scholar 

  29. Johnson AG, Nguyen TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med 1994 Aug 15; 121(4): 289–300

    PubMed  CAS  Google Scholar 

  30. Houston MC. Nonsteroidal anti-inflammatory drugs and anti-hypertensives. Am J Med 1991 May 17; 90(5A): 42S–7S

    Article  PubMed  CAS  Google Scholar 

  31. Koopmans PP. Pathophysiological and clinical aspects of the interaction between non-steroidal anti-inflammatory drugs (NSAID) and diuretics. Neth J Med 1985; 28(11): 524–9

    PubMed  CAS  Google Scholar 

  32. Sturrock ND, Struthers AD. Non-steroidal anti-inflammatory drugs and angiotensin converting enzyme inhibitors: a commonly prescribed combination with variable effects on renal function. Br J Clin Pharmacol 1993 Apr; 35(4): 343–8

    Article  PubMed  CAS  Google Scholar 

  33. Brater DC. Effects of nonsteroidal anti-inflammatory drugs on renal function: focus on cyclooxygenase-2-selective inhibition. Am J Med 1999 Dec 13; 107(6A): 65S–71S

    Article  PubMed  CAS  Google Scholar 

  34. Cangiano JL, Figueroa J, Palmer R. Renal hemodynamic effects of nabumetone, sulindac, and placebo in patients with osteoar-thritis. Clin Ther 1999 Mar; 21(3): 503–12

    Article  PubMed  CAS  Google Scholar 

  35. Freed MI, Audet PR, Zariffa N, et al. Comparative effects of nabumetone, sulindac, and indomethacin on urinary prostaglandin excretion and platelet function in volunteers. J Clin Pharmacol 1994 Nov; 34(11): 1098–108

    PubMed  CAS  Google Scholar 

  36. Cook ME, Wallin JD, Thakur VD, et al. Comparative effects of nabumetone, sulindac, and ibuprofen on renal function. J Rheumatol 1997 Jun; 24(6): 1137–44

    PubMed  CAS  Google Scholar 

  37. Sedor JR, Williams SL, Chremos AN, et al. Effects of sulindac and indomethacin on renal prostaglandin synthesis. Clin Pharmacol Ther 1984 Jul; 36(1): 85–91

    Article  PubMed  CAS  Google Scholar 

  38. Murray MD, Black PK, Kuzmik DD, et al. Acute and chronic effects of nonsteroidal antiinflammatory drugs on glomerular filtration rate in elderly patients. Am J Med Sci 1995 Nov; 310(5): 188–97

    Article  PubMed  CAS  Google Scholar 

  39. Murray MD, Lazaridis EN, Brizendine E, et al. The effect of nonsteroidal antiinflammatory drugs on electrolyte homeostasis and blood pressure in young and elderly persons with and without renal insufficiency. Am J Med Sci 1997 Aug; 314(2): 80–8

    Article  PubMed  CAS  Google Scholar 

  40. Aronoff GR. Therapeutic implications associated with renal studies of nabumetone. J Rheumatol 1992 Nov; 19 Suppl. 36: 25–31

    CAS  Google Scholar 

  41. Skeith KJ, Wright M, Davis P. Differences in NSAID tolerability profiles. Fact or fiction? Drug Saf 1994 Mar; 10(3): 183–95

    Article  PubMed  CAS  Google Scholar 

  42. Ofran Y, Bursztyn M, Ackerman Z. Rofecoxib-induced renal dysfunction in a patient with compensated cirrhosis and heart failure. Am J Gastroenterol 2001 Jun; 96(6): 1941

    Article  PubMed  CAS  Google Scholar 

  43. Perazella MA, Tray K. Selective cyclooxygenase-2 inhibitors: a pattern of nephrotoxicity similar to traditional nonsteroidal anti-inflammatory drugs. Am J Med 2001 Jul; 111(1): 64–7

    Article  PubMed  CAS  Google Scholar 

  44. Pitkala KH, Strandberg TE, Tilvis RS. Worsening heart failure associated with COX-2 inhibitors. Am J Med 2002 Apr; 112(5): 424–6

    Article  PubMed  Google Scholar 

  45. Henao J, Hisamuddin I, Nzerue CM, et al. Celecoxib-induced acute interstitial nephritis. Am J Kidney Dis 2002 Jun; 39(6): 1313–7

    Article  PubMed  Google Scholar 

  46. Fitzgerald GA. Cardiovascular pharmacology of nonselective nonsteroidal anti-inflammatory drugs and coxibs: clinical considerations. Am J Cardiol 2002 Mar 21; 89(6A): 26D–32D

    Article  PubMed  CAS  Google Scholar 

  47. Harris RC, McKanna JA, Akai Y, et al. Cyxlooxygenase-2 is associated with the macula densa of rat kidney and increases with salt restriction. J Clin Invest 1994 Dec; 94(6): 2504–10

    Article  PubMed  CAS  Google Scholar 

  48. Khan KNM, Venturini CM, Bunch RT, et al. Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal anti-inflammatory drug-related nephrotoxicity. Toxicol Pathol 1998 Sep–Oct; 26(5): 612–20

    PubMed  CAS  Google Scholar 

  49. Vio CP, Cespedes C, Gallardo P, et al. Renal identification of cyclooxygenase-2 in a subset of thick ascending limb cells. Hypertension 1997 Sep; 30 (3 Pt 2): 687–92

    Article  PubMed  CAS  Google Scholar 

  50. O'Neill GP, Ford-Hutchinson AW. Expression of mRNA for cyclooxygenase-1 and cyclooxygenase-2 in human tissues. FEBS Lett 1993 Sep 13; 330(2): 156–60

    Article  PubMed  Google Scholar 

  51. Kömhoff M, Gröne HJ, Klein T, et al. Localization of cyclooxygenase-1 and -2 in adult and fetal human kidney: implication for renal function. Am J Physiol 1997 Apr; 272 (4 Pt 2): F460–8

    PubMed  Google Scholar 

  52. Guan Y, Chang M, Cho W, et al. Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells. Am J Physiol 1997 Jul; 273 (1 Pt 2): F18–26

    PubMed  CAS  Google Scholar 

  53. Harris RC. Cyclooxygenase-2 inhibition and renal physiology. Am J Cardiol 2002 Mar 21; 89(6A): 10D–7D

    Article  PubMed  CAS  Google Scholar 

  54. Hao CM, Yull F, Blackwell T, et al. Dehydration activates a NF-kappaB-driven, COX-2-dependent survival mechanism in renal medullary interstitial cells. J Clin Invest 2000 Oct; 106(8): 973–82

    Article  PubMed  CAS  Google Scholar 

  55. Yang T, Singh I, Pham H, et al. Regulation of cyclooxygenase expression in the kidney by dietary salt intake. Am J Physiol 1998 Mar; 274 (3 Pt 2): F481–9

    PubMed  CAS  Google Scholar 

  56. Yang T, Schnermann JB, Briggs JP. Regulation of cyclooxygenase-2 expression in renal medulla by tonicity in vivo and in vitro. Am J Physiol 1999 Jul; 277 (1 Pt 2): Fl–9

    Google Scholar 

  57. Cheng HF, Wang JL, Zhang MZ, et al. Angiotensin II attenuates renal cortical cyclooxygenase-2 expression. J Clin Invest 1999 Apr; 103(7): 953–61

    Article  PubMed  CAS  Google Scholar 

  58. Whelton A, Schulman G, Wallemark C, et al. Effects of celecoxib and naproxen on renal function in the elderly. Arch Intern Med 2000 May 22; 160(10): 1465–70

    Article  PubMed  CAS  Google Scholar 

  59. Catella-Lawson F, McAdam B, Morrison BW, et al. Effects of specific inhibition of cyclooxygenase-2 on sodium balance, hemodynamics, and vasoactive eicosanoids. J Pharmacol Exp Ther 1999 May; 289(2): 735–41

    PubMed  CAS  Google Scholar 

  60. Swan SK, Rudy DW, Lasseter KC, et al. Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet. A randomized, controlled trial. Ann Intern Med 2000 Jul 4; 133(1): 1–9

    CAS  Google Scholar 

  61. Rossat J, Maillard M, Nussberger J, et al. Renal effects of selective cyclooxygenase-2 inhibition in normotensive salt-depleted subjects. Clin Pharmacol Ther 1999 Jul; 66(1): 76–84

    Article  PubMed  CAS  Google Scholar 

  62. Frishman WH. Effects of nonsteroidal anti-inflammatory drug therapy on blood pressure and peripheral edema. Am J Cardiol 2002 Mar 21; 89(6A): 18D–25D

    Article  PubMed  CAS  Google Scholar 

  63. Whelton A, Fort JG, Puma JA, et al., SUCCESS VI Study Group. Cyclooxygenase-2-specific inhibitors and cardiorenal function: a randomized, controlled trial of celecoxib and rofecoxib in older hypertensive osteoarthritis patients. Am J Ther 2001 Mar–Apr; 8(2): 85–95

    Article  PubMed  CAS  Google Scholar 

  64. Silverstein FE, Faich G, Goldstein JL, et al. Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. The CLASS study: a randomized controlled trial. JAMA 2000 Sep 13; 284(10): 1247–55

    Article  PubMed  CAS  Google Scholar 

  65. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA 2001 Aug 22–29; 286(8): 954–9

    Article  PubMed  CAS  Google Scholar 

  66. Bombardier C, Laine L, Reicin A, et al. Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR study group. N Engl J Med 2000 Nov 23; 343(21): 1520–8

    Article  CAS  Google Scholar 

  67. White WB, Faich G, Whelton A, et al. Comparison of thrombo-embolic events in patients treated with celecoxib, a cyclooxygenase-2 specific inhibitor, versus ibuprofen or diclofenac. Am J Cardiol 2002 Feb 15; 89(4): 425–30

    Article  PubMed  CAS  Google Scholar 

  68. Konstam MA, Weir MR, Reicin A, et al. Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib. Circulation 2001 Nov 6; 104(19): 2280–8

    Article  PubMed  CAS  Google Scholar 

  69. Mukherjee D. Selective cyclooxygenase-2 (COX-2) inhibitors and potential risk of cardiovascular events. Biochem Pharmacol 2002 Mar 1; 63(5): 817–21

    Article  PubMed  CAS  Google Scholar 

  70. Ray WA, Stein CM, Hall K, et al. Non-steroidal anti-inflammatory drugs and risk of serious coronary heart disease: an observational study. Lancet 2002 Jan 12; 359(9301): 118–23

    Article  PubMed  CAS  Google Scholar 

  71. Solomon DH, Glynn RJ, Levin R, et al. Nonsteroidal anti-inflammatory drug use and acute myocardial infarction. Arch Inetrn Med 2002 May 27; 162(10): 1099–104

    Article  CAS  Google Scholar 

  72. Watson DJ, Rhodes T, Cai B, et al. Lower risk of thromboembolic cardiovascular events with naproxen among patients with rheumatoid arthritis. Arch Intern Med May 27; 162(10): 1105–10

  73. Rahme E, Pilote L, LeLorier J. Association between naproxen use and protection against acute myocardial infarction. Arch Intern Med 2002 May 27; 162(10): 1111–5

    Article  PubMed  CAS  Google Scholar 

  74. Heerdink ER, Leufkens HG, Herings RMC, et al. NSAIDs associated with increased risk of congestive heart failure in elderly patients taking diuretics. Arch Intern Med 1998 May 25; 158(10): 1108–12

    Article  PubMed  CAS  Google Scholar 

  75. Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an under-recognized public health problem. Arch Intern Med 2000 Mar 27; 160(6): 777–84

    Article  PubMed  CAS  Google Scholar 

  76. Feenstra J. Adverse cardiovascular effects of drugs in patients with heart failure [thesis]. Rotterdam: Erasmus Medical Centre Rotterdam, 2000

    Google Scholar 

  77. Merlo J, Broms K, Lindblad U, et al. Association of outpatient utilisation of non-steroidal anti-inflammatory drugs and hospitalised heart failure in the entire Swedish population. Eur J Clin Pharmacol 2001 Apr; 57(1): 71–5

    Article  PubMed  CAS  Google Scholar 

  78. Feenstra J, Heerdink ER, Grobbee DE, et al. Association of nonsteroidal anti-inflammatory drugs with first occurrence of heart failure and with relapsing heart failure: the Rotterdam Study. Arch Intern Med 2002 Feb 11; 162(3): 265–7

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this manuscript.

Author information

Authors and Affiliations

  1. Department of Epidemiology & Biostatistics, Erasmus Medical Centre, Rotterdam, The Netherlands

    Gysèle S. Bleumink, Miriam C. J. M. Sturkenboom & Bruno H. Ch. Stricker

  2. Inspectorate for Healthcare, The Hague, The Netherlands

    Gysèle S. Bleumink & Bruno H. Ch. Stricker

  3. Department of Internal Medicine, Albert Schweitzer Hospital, Dordrecht, The Netherlands

    Johannes Feenstra

Authors
  1. Gysèle S. Bleumink
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Johannes Feenstra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miriam C. J. M. Sturkenboom
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bruno H. Ch. Stricker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bruno H. Ch. Stricker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bleumink, G.S., Feenstra, J., Sturkenboom, M.C.J.M. et al. Nonsteroidal Anti-Inflammatory Drugs and Heart Failure. Drugs 63, 525–534 (2003). https://doi.org/10.2165/00003495-200363060-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200363060-00001

Keywords

Search

Navigation