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Cardiovascular risk associated with nonsteroidal anti-inflammatory drugs

Current Rheumatology Reports volume 11, pages 31–35 (2009)Cite this article

Abstract

Since the introduction of selective cyclooxygenase-2 inhibitors (coxibs), there has been an ongoing discussion about the cardiovascular (CV) safety of coxibs and the traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Available data about the CV safety of NSAIDs come mostly from meta-analyses and a few clinical trials. Current evidence suggests that NSAIDs may increase the risk of CV events. Naproxen might be associated with lower risk, but available data are not conclusive. Recent recommendations on the treatment of patients with NSAIDs favor the use of naproxen in patients with increased CV risk. Therefore, this review focuses on data about naproxen and examines CV risk with ibuprofen and non-naproxen NSAIDs. In addition, data about CV safety of paracetamol (acetaminophen) are presented.

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References and Recommended Reading

  1. Graham DJ, Campen D, Hui R, et al.: Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study. Lancet 2005, 365:475–481.

    PubMed  Article  CAS  Google Scholar 

  2. Chan AT, Manson JE, Albert CM, et al.: Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation 2006, 113:1578–1587.

    PubMed  Article  CAS  Google Scholar 

  3. Forman JP, Stampfer MJ, Curhan GC: Non-narcotic analgesic dose and risk of incident hypertension in US women. Hypertension 2005, 46:500–507.

    PubMed  Article  CAS  Google Scholar 

  4. Warner TD, Mitchell JA: COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs. Lancet 2008, 371:270–273.

    PubMed  Article  CAS  Google Scholar 

  5. Kearney PM, Baigent C, Godwin J, et al.: Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ 2006, 332:1302–1308.

    PubMed  Article  CAS  Google Scholar 

  6. McGettigan P, Henry D: Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA 2006, 296:1633–1644.

    PubMed  Article  CAS  Google Scholar 

  7. Andersohn F, Schade R, Suissa S, Garbe E: Cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs and the risk of ischemic stroke: a nested case-control study. Stroke 2006, 37:1725–1730.

    PubMed  Article  CAS  Google Scholar 

  8. Singh G, Wu O, Langhorne P, Madhok R: Risk of acute myocardial infarction with nonselective non-steroidal antiinflammatory drugs: a meta-analysis. Arthritis Res Ther 2006, 8:R153.

    PubMed  Article  Google Scholar 

  9. Salpeter SR, Gregor P, Ormiston TM, et al.: Meta-analysis: cardiovascular events associated with nonsteroidal antiinflammatory drugs. Am J Med 2006, 119:552–559.

    PubMed  Article  CAS  Google Scholar 

  10. 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, 343:1520–1528.

    PubMed  Article  CAS  Google Scholar 

  11. Juni P, Nartey L, Reichenbach S, et al.: Risk of cardiovascular events and rofecoxib: cumulative meta-analysis. Lancet 2004, 364:2021–2029.

    PubMed  Article  CAS  Google Scholar 

  12. Hippisley-Cox J, Coupland C: Risk of myocardial infarction in patients taking cyclo-oxygenase-2 inhibitors or conventional non-steroidal anti-inflammatory drugs: population based nested case-control analysis. BMJ 2005, 330:1366.

    PubMed  Article  CAS  Google Scholar 

  13. Cardiovascular and Cerebrovascular Events in the Randomized, Controlled Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT). PLoS Clinical Trials 2006, 1:e33.

  14. Capone ML, Sciulli MG, Tacconelli S, et al.: Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects. J Am Coll Cardiol 2005, 45:1295–1301.

    PubMed  Article  CAS  Google Scholar 

  15. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002, 324:71–86.

  16. Graham I, Atar D, Borch-Johnsen K, et al.: European guidelines on cardiovascular disease prevention in clinical practice: executive summary. Eur Heart J 2007, 28:2375–2414.

    PubMed  Article  Google Scholar 

  17. Catella-Lawson F, Reilly MP, Kapoor SC, et al.: Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med 2001, 345:1809–1817.

    PubMed  Article  CAS  Google Scholar 

  18. Farkouh ME, Greenberg JD, Jeger RV, et al.: Cardiovascular outcomes in high risk patients with osteoarthritis treated with ibuprofen, naproxen or lumiracoxib. Ann Rheum Dis 2007, 66:764–770.

    PubMed  Article  CAS  Google Scholar 

  19. Solomon DH, Glynn RJ, Rothman KJ, et al.: Subgroup analyses to determine cardiovascular risk associated with nonsteroidal antiinflammatory drugs and coxibs in specific patient groups. Arthritis Rheum 2008, 59:1097–1104.

    PubMed  Article  Google Scholar 

  20. Antman EM, Bennett JS, Daugherty A, et al.: Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation 2007, 115:1634–1642.

    PubMed  Article  Google Scholar 

  21. Chan FK, Abraham NS, Scheiman JM, Laine L: Management of patients on nonsteroidal anti-inflammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Antiplatelet Agents. Am J Gastroenterol 2008 (in press).

  22. Forman JP, Rimm EB, Curhan GC: Frequency of analgesic use and risk of hypertension among men. Arch Intern Med 2007, 167:394–399.

    PubMed  Article  Google Scholar 

  23. Montgomery B: Does paracetamol cause hypertension? BMJ 2008, 336:1190–1191.

    PubMed  Article  Google Scholar 

  24. Sudano I, Flammer AJ, Periat D, et al.: Paracetamol increases 24-hour blood pressure in patients with stable coronary artery disease. Paper presented at 18th Scientific Meeting of the European Society of Hypertension/22nd Scientific Meeting of the International Society of Hypertension. Berlin, Germany, 2008.

  25. Aw TJ, Haas SJ, Liew D, Krum H: Meta-analysis of cyclooxygenase-2 inhibitors and their effects on blood pressure. Arch Intern Med 2005, 165:490–496.

    PubMed  Article  CAS  Google Scholar 

  26. Bresalier RS, Sandler RS, Quan H, et al.: Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial. N Engl J Med 2005, 352:1092–1102.

    PubMed  Article  CAS  Google Scholar 

  27. Solomon SD, McMurray JJ, Pfeffer MA, et al.: Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention. N Engl J Med 2005, 352:1071–1080.

    PubMed  Article  CAS  Google Scholar 

  28. Kurth T, Hennekens CH, Sturmer T, et al.: Analgesic use and risk of subsequent hypertension in apparently healthy men. Arch Intern Med 2005, 165:1903–1909.

    PubMed  Article  Google Scholar 

  29. Chenevard R, Hurlimann D, Bechir M, et al.: Selective COX-2 inhibition improves endothelial function in coronary artery disease. Circulation 2003, 107:405–409.

    PubMed  Article  Google Scholar 

  30. Berndt G, Grosser N, Hoogstraate J, Schroder H: A common pathway of nitric oxide release from AZD3582 and glyceryl trinitrate. Eur J Pharm Sci 2004, 21:331–335.

    PubMed  Article  CAS  Google Scholar 

  31. Rossoni G, Manfredi B, Del Soldato P, Berti F: The nitric oxide-releasing naproxen derivative displays cardioprotection in perfused rabbit heart submitted to ischemia-reperfusion. J Pharmacol Exp Ther 2004, 310:555–562.

    PubMed  Article  CAS  Google Scholar 

  32. Hawkey CJ, Jones JI, Atherton CT, et al.: Gastrointestinal safety of AZD3582, a cyclooxygenase inhibiting nitric oxide donator: proof of concept study in humans. Gut 2003, 52:1537–1542.

    PubMed  Article  CAS  Google Scholar 

  33. Romero-Sandoval EA, Mazario J, Howat D, Herrero JF: NCX-701 (nitroparacetamol) is an effective antinociceptive agent in rat withdrawal reflexes and wind-up. Br J Pharmacol 2002, 135:1556–1562.

    PubMed  Article  CAS  Google Scholar 

  34. Zhu YZ, Chong CL, Chuah SC, et al.: Cardioprotective effects of nitroparacetamol and paracetamol in acute phase of myocardial infarction in experimental rats. Am J Physiol Heart Circ Physiol 2006, 290:H517–H524.

    PubMed  Article  CAS  Google Scholar 

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Affiliations

  1. Department of Cardiology, University Hospital Zürich, Ramistrasse 100, CH-8091, Zürich, Switzerland

    Matthias Hermann

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  1. Matthias Hermann
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Correspondence to Matthias Hermann.

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Hermann, M. Cardiovascular risk associated with nonsteroidal anti-inflammatory drugs. Curr Rheumatol Rep 11, 31–35 (2009). https://doi.org/10.1007/s11926-009-0005-5

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  • DOI: https://doi.org/10.1007/s11926-009-0005-5

Keywords

  • Ibuprofen
  • Paracetamol
  • Celecoxib
  • Naproxen
  • Rofecoxib