Display options
Share it on

Drug Saf. 2006;29(7):567-86. doi: 10.2165/00002018-200629070-00003.

Heart failure induced by non-cardiac drugs.

Drug safety

Lars Slørdal, Olav Spigset

Affiliations

  1. Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway. [email protected]

PMID: 16808550 DOI: 10.2165/00002018-200629070-00003

Abstract

Although heart failure is predominantly caused by cardiovascular conditions such as hypertension, coronary heart disease and valvular heart disease, it can also be an adverse reaction induced by drug therapy. In addition, some drugs have the propensity to adversely affect haemodynamic mechanisms in patients with an already existing heart condition. In this article, non-cardiac drugs known to be associated with the development or worsening of heart failure are reviewed. Moreover, drugs that may adversely affect the heart as a pump without causing symptoms or signs of heart failure are also included. The drugs discussed include anticancer agents such as anthracyclines, mitoxantrone, cyclophosphamide, fluorouracil, capecitabine and trastuzumab; immunomodulating drugs such as interferon-alpha-2, interleukin-2, infliximab and etanercept; antidiabetic drugs such as rosiglitazone, pioglitazone and troglitazone; antimigraine drugs such as ergotamine and methysergide; appetite suppressants such as fenfulramine, dexfenfluramine and phentermine; tricyclic antidepressants; antipsychotic drugs such as clozapine; antiparkinsonian drugs such as pergolide and cabergoline; glucocorticoids; and antifungal drugs such as itraconazole and amphotericin B. NSAIDs, including selective cyclo-oxygenase (COX)-2 inhibitors, are included as a result of their ability to cause heart disease, particularly in patients with an already existing cardiorenal dysfunction. Two drug groups are of particular concern. Anthracyclines and their derivatives may cause cardiomyopathy in a disturbingly high number of exposed individuals, who may develop symptoms of insidious onset several years after drug therapy. The risk seems to encompass all exposed individuals, but data suggest that children are particularly vulnerable. Thus, a high degree of awareness towards this particular problem is warranted in cancer survivors subjected to anthracycline-based chemotherapy. A second group of problematic drugs are the NSAIDs, including the selective COX-2 inhibitors. These drugs may cause renal dysfunction and elevated blood pressure, which in turn may precipitate heart failure in vulnerable individuals. Although NSAID-related cardiotoxicity is relatively rare and most commonly seen in elderly individuals with concomitant disease, the widespread long-term use of these drugs in risk groups is potentially hazardous. Pending comprehensive safety analyses, the use of NSAIDs in high-risk patients should be discouraged. In addition, there is an urgent need to resolve the safety issues related to the use of COX-2 inhibitors. As numerous drugs from various drug classes may precipitate or worsen heart failure, a detailed history of drug exposure in patients with signs or symptoms of heart failure is mandatory.

References

  1. Drugs Aging. 1998 Jan;12(1):17-27 - PubMed
  2. N Engl J Med. 2004 Jul 8;351(2):145-53 - PubMed
  3. BMJ. 1994 Apr 30;308(6937):1162 - PubMed
  4. CMAJ. 2002 Jan 22;166(2):219 - PubMed
  5. Circulation. 2000 May 2;101(17 ):2071-7 - PubMed
  6. J Pediatr. 1998 Mar;132(3 Pt 1):550-2 - PubMed
  7. Am J Psychiatry. 1991 Nov;148(11):1601 - PubMed
  8. Am Heart J. 1985 May;109(5 Pt 1):992-8 - PubMed
  9. Breast. 2004 Jun;13(3):171-2 - PubMed
  10. Eur J Heart Fail. 2002 Jun;4(3):235-42 - PubMed
  11. Ann Intern Med. 1979 Nov;91(5):710-7 - PubMed
  12. N Engl J Med. 2005 Mar 17;352(11):1092-102 - PubMed
  13. Mov Disord. 2004 Jun;19(6):656-62 - PubMed
  14. Cancer. 2003 Jun 1;97(11):2869-79 - PubMed
  15. J Cancer Res Clin Oncol. 2004 Jan;130(1):1-7 - PubMed
  16. Mayo Clin Proc. 1999 Apr;74(4):371-5 - PubMed
  17. Ann Intern Med. 1994 Aug 15;121(4):289-300 - PubMed
  18. J Clin Oncol. 2002 Mar 1;20(5):1215-21 - PubMed
  19. Br J Clin Pharmacol. 2002 Sep;54(3):327-32 - PubMed
  20. JAMA. 1994 Sep 14;272(10):781-6 - PubMed
  21. Cardiovasc Res. 2004 Nov 1;64(2):217-26 - PubMed
  22. J Clin Oncol. 2002 Feb 1;20(3):719-26 - PubMed
  23. Cancer. 1994 Nov 15;74(10):2850-6 - PubMed
  24. JAMA. 2000 Apr 5;283(13):1703-9 - PubMed
  25. JAMA. 2000 Sep 13;284(10):1247-55 - PubMed
  26. J Toxicol Environ Health. 1984;14(2-3):137-43 - PubMed
  27. Am J Med. 1987 Jun;82(6):1109-18 - PubMed
  28. Curr Probl Cancer. 1997 Nov-Dec;21(6):301-60 - PubMed
  29. Arch Intern Med. 1993 Feb 22;153(4):477-84 - PubMed
  30. Epidemiology. 2003 Mar;14 (2):240-6 - PubMed
  31. Cancer. 1998 Sep 15;83(6):1231-6 - PubMed
  32. Drug Saf. 1997 Sep;17(3):166-80 - PubMed
  33. Arch Intern Med. 2002 May 27;162(10):1099-104 - PubMed
  34. Heart. 2004 Aug;90(8):e47 - PubMed
  35. Circulation. 1993 Apr;87(4):1340-53 - PubMed
  36. Am J Med. 1994 Dec;97(6):560-2 - PubMed
  37. Cancer. 1990 Feb 15;65(4):870-3 - PubMed
  38. Drug Saf. 2001;24(12):903-20 - PubMed
  39. Mayo Clin Proc. 2002 Dec;77(12 ):1280-6 - PubMed
  40. Cancer. 1990 Oct 1;66(7):1513-6 - PubMed
  41. Drugs. 2003;63(6):525-34 - PubMed
  42. JAMA. 1991 Sep 25;266(12 ):1672-7 - PubMed
  43. Neurology. 2003 Sep 23;61(6):859-61 - PubMed
  44. Lancet. 2004 May 29;363(9423):1751-6 - PubMed
  45. J Clin Oncol. 2002 Mar 15;20(6):1677-82 - PubMed
  46. Oncologist. 2003;8 Suppl 2:17-24 - PubMed
  47. Cancer. 1989 Jan 1;63(1):37-45 - PubMed
  48. J Am Soc Echocardiogr. 2002 Jun;15(6):653-7 - PubMed
  49. Am J Cardiol. 2002 Mar 21;89(6A):18D-25D - PubMed
  50. Cancer Treat Rev. 2004 Apr;30(2):181-91 - PubMed
  51. N Engl J Med. 1989 Nov 2;321(18):1246-9 - PubMed
  52. BMJ. 2002 Aug 3;325(7358):269-71 - PubMed
  53. Am Heart J. 2002 Sep;144(3):508-15 - PubMed
  54. Br J Haematol. 2004 Feb;124(4):463-8 - PubMed
  55. Circulation. 2004 Mar 23;109 (11):1428-33 - PubMed
  56. Methods Enzymol. 1990;186:611-21 - PubMed
  57. Ann Intern Med. 2003 May 20;138(10):807-11 - PubMed
  58. Lancet. 1999 Jan 23;353(9149):307-14 - PubMed
  59. Annu Rev Med. 2001;52:239-57 - PubMed
  60. Med Sci Monit. 2000 Mar-Apr;6(2):411-20 - PubMed
  61. J Am Coll Cardiol. 2003 Apr 16;41(8):1394-8 - PubMed
  62. Cancer Treat Rep. 1976 Jul;60(7):813-22 - PubMed
  63. Drugs. 2000 Jun;59(6):1207-16 - PubMed
  64. N Engl J Med. 1991 Mar 21;324(12):808-15 - PubMed
  65. N Engl J Med. 1998 Sep 10;339(11):725-32 - PubMed
  66. Cancer Treat Rep. 1978 Jun;62(6):955-61 - PubMed
  67. N Engl J Med. 2001 Dec 6;345(23):1689-97 - PubMed
  68. Pediatr Blood Cancer. 2004 Mar;42(3):220-4 - PubMed
  69. J Am Coll Cardiol. 1999 Apr;33(5):1152-62 - PubMed
  70. J R Soc Promot Health. 2000 Jun;120(2):83-9 - PubMed
  71. J Immunother (1991). 1992 Apr;11(3):225-9 - PubMed
  72. N Engl J Med. 1998 Sep 24;339(13):900-5 - PubMed
  73. Arch Intern Med. 2005 May 9;165(9):978-84 - PubMed
  74. Cancer. 1967 Mar;20(3):333-53 - PubMed
  75. J Clin Oncol. 2003 Jun 15;21(12 ):2349-56 - PubMed
  76. Arthritis Rheum. 1991 Sep;34(9):1207 - PubMed
  77. Circulation. 2003 Jul 1;107(25):3133-40 - PubMed
  78. Lancet. 2002 Oct 5;360(9339):1071-3 - PubMed
  79. Drugs. 1998 Jan;55(1):5-30 - PubMed
  80. Drug Saf. 2002;25(5):301-11 - PubMed
  81. Arch Intern Med. 2002 May 27;162(10):1111-5 - PubMed
  82. J Antimicrob Chemother. 2004 Jan;53(1):115-7 - PubMed
  83. BMJ. 1990 May 5;300(6733):1174-5 - PubMed
  84. Br Med J. 1979 Sep 15;2(6191):668 - PubMed
  85. Can J Cardiol. 2000 Apr;16(4):505-11 - PubMed
  86. Diabetes Care. 2003 Nov;26(11):2983-9 - PubMed
  87. Diabetes Obes Metab. 2004 Jan;6(1):50-5 - PubMed
  88. Semin Oncol. 1998 Aug;25(4 Suppl 10):72-85 - PubMed
  89. Arch Intern Med. 1998 May 25;158(10):1108-12 - PubMed
  90. Ann Hematol. 2003 Apr;82(4):218-22 - PubMed
  91. J Clin Psychiatry. 1989 Oct;50(10):368-78 - PubMed
  92. Am J Med Sci. 2001 Apr;321(4):285-91 - PubMed
  93. Breast. 2004 Jun;13(3):173-83 - PubMed
  94. Lancet. 1999 Nov 27;354(9193):1841-5 - PubMed
  95. JAMA. 2001 Oct 24-31;286(16):2011-4 - PubMed
  96. Heart. 2004 Aug;90(8):859-65 - PubMed
  97. Circulation. 1999 Jun 29;99(25):3224-6 - PubMed
  98. Eur J Clin Pharmacol. 2001 Apr;57(1):71-5 - PubMed
  99. Ann Intern Med. 1982 Feb;96(2):133-9 - PubMed
  100. Lancet. 2001 Jun 2;357(9270):1766-7 - PubMed
  101. Am J Med. 1999 May 31;106(5B):13S-24S - PubMed
  102. Am J Psychiatry. 1998 May;155(5):660-5 - PubMed
  103. Drug Saf. 2000 Apr;22(4):263-302 - PubMed
  104. N Engl J Med. 2001 Mar 15;344(11):783-92 - PubMed
  105. Semin Oncol. 1982 Mar;9(1):23-33 - PubMed
  106. J Clin Oncol. 1999 Sep;17(9):2639-48 - PubMed
  107. Br Med J. 1978 Sep 2;2(6138):666-7 - PubMed
  108. Circulation. 1995 Mar 15;91(6):1619-23 - PubMed
  109. Arch Pathol Lab Med. 1990 Jan;114(1):62-4 - PubMed
  110. Circulation. 2004 Jun 8;109(22):2749-54 - PubMed
  111. JAMA. 2001 Aug 22-29;286(8):954-9 - PubMed
  112. Am Rev Respir Dis. 1971 Jun;103(6):831-41 - PubMed
  113. J Clin Invest. 2001 Aug;108(4):585-90 - PubMed
  114. Cancer Treat Rep. 1980 Jan;64(1):47-51 - PubMed
  115. Circulation. 2003 Mar 18;107(10):1350-4 - PubMed
  116. Chest. 2000 Mar;117(3):870-4 - PubMed
  117. Arch Intern Med. 2002 Feb 11;162(3):265-70 - PubMed
  118. Adverse Drug React Toxicol Rev. 2002;21(4):219-29 - PubMed
  119. Arch Intern Med. 2002 May 27;162(10):1105-10 - PubMed
  120. Ann Oncol. 2002 May;13(5):710-5 - PubMed
  121. J Intern Med. 2002 Mar;251(3):228-34 - PubMed
  122. J Clin Oncol. 1995 Nov;13(11):2688-99 - PubMed
  123. Arch Intern Med. 2005 Mar 14;165(5):490-6 - PubMed
  124. Circulation. 2001 Feb 27;103(8):1044-7 - PubMed
  125. Circulation. 1997 Oct 21;96(8):2641-8 - PubMed
  126. BMJ. 2001 May 19;322(7296):1207-9 - PubMed
  127. BMJ. 2005 Jun 11;330(7504):1370 - PubMed
  128. Am J Med Sci. 2002 Dec;324(6):331-4 - PubMed
  129. Br Med J. 1979 Aug 4;2(6185):308 - PubMed
  130. Cancer. 1994 Dec 15;74(12):3212-22 - PubMed
  131. Lancet. 2002 Jan 12;359(9301):118-23 - PubMed
  132. Hum Pathol. 1990 May;21(5):493-502 - PubMed
  133. Cancer. 2004 May 15;100(10):2052-63 - PubMed
  134. Arch Pathol Lab Med. 1989 Aug;113(8):838-41 - PubMed
  135. Br J Clin Pharmacol. 1993 May;35(5):455-9 - PubMed
  136. Ann Oncol. 2002 May;13(5):699-709 - PubMed
  137. N Engl J Med. 2005 Mar 17;352(11):1071-80 - PubMed
  138. Arch Intern Med. 2000 Mar 27;160(6):777-84 - PubMed
  139. Intern Med. 1992 Jul;31(7):936-40 - PubMed
  140. Chest. 1991 Mar;99(3):557-61 - PubMed
  141. N Engl J Med. 2000 Nov 23;343 (21):1520-8, 2 p following 1528 - PubMed
  142. BMJ. 2005 Jun 11;330(7504):1366 - PubMed
  143. Ann Intern Med. 2004 Nov 16;141(10):764-70 - PubMed
  144. Arch Intern Med. 2003 Feb 24;163(4):481-6 - PubMed
  145. N Engl J Med. 1982 Apr 22;306(16):954-9 - PubMed
  146. J Clin Psychopharmacol. 2001 Aug;21(4):382-8 - PubMed
  147. Am Heart J. 1974 Nov;88(5):640-55 - PubMed
  148. Lancet. 2005 Feb 5-11;365(9458):475-81 - PubMed
  149. N Engl J Med. 1991 Oct 24;325(17):1223-7 - PubMed
  150. N Engl J Med. 1996 Aug 29;335(9):609-16 - PubMed

MeSH terms

Publication Types