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Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs

  • Carlo PatronoEmail author
Ischemic Heart Disease (D Mukherjee, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Ischemic Heart Disease

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) include aspirin, other traditional NSAIDs, and coxibs. Evidence obtained during the past 10 years has focused attention on the cardiovascular hazard associated with coxibs and some traditional NSAIDs. The large randomized trials of prolonged coxib treatment added importantly to information provided by epidemiological studies that had previously associated regular use of NSAIDs with increased blood pressure and enhanced risk of congestive heart failure, and identified an increased risk of myocardial infarction as a class effect of cyclooxygenase-2 inhibitors. The aim of this article is to review the cardiovascular effects of aspirin, other traditional NSAIDs, and coxibs, to discuss the mechanisms underlying these effects, and to provide a clinical perspective on the cardiovascular hazard associated with their use.

Keywords

Aspirin Atherothrombosis Coxib Cyclooxygenase inhibitors Diclofenac Heart failure Ibuprofen Naproxen 

Notes

Compliance with Ethics Standards

Conflict of Interest

Carlo Patrono declares that he is a member of the Scientific Advisory Board of the Aspirin Foundation and he has received consultant and speaker fees from AstraZeneca and Bayer and an institutional grant from Bayer AG for investigator-initiated research.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Patrono C. Nonsteroidal antiinflammatory drugs. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, editors. Rheumatology. 6th ed. Philadelphia: Elsevier Mosby; 2015. p. 415–22.Google Scholar
  2. 2.
    FitzGerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001;345:433–42.CrossRefPubMedGoogle Scholar
  3. 3.•
    Patrignani P, Patrono C. Cyclooxygenase inhibitors: from pharmacology to clinical read-outs. Biochim Biophys Acta. 2015;1851:422–32. This article reviews in detail the human pharmacology of cyclooxygenase inhibitors.CrossRefPubMedGoogle Scholar
  4. 4.
    de Abajo FJ, Gil MJ, Bryant V, et al. Upper gastrointestinal bleeding associated with NSAIDs, other drugs and interactions: a nested case-control study in a new general practice database. Eur J Clin Pharmacol. 2013;69:691–701.CrossRefPubMedGoogle Scholar
  5. 5.
    Patrono C, Baigent C. Nonsteroidal anti-inflammatory drugs and the heart. Circulation. 2014;129:907–16.CrossRefPubMedGoogle Scholar
  6. 6.••
    Coxib and traditional NSAID Trialists' (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013;382:769–79. These meta-analyses provide the most reliable and comprehensive source of information on the cardiovascular and gastrointestinal effects of coxibs and traditional NSAIDs.CrossRefGoogle Scholar
  7. 7.
    Patrignani P, Panara MR, Greco A, et al. Biochemical and pharmacological characterization of the cyclooxygenase activity of human blood prostaglandin endoperoxide synthases. J Pharmacol Exp Ther. 1994;271:1705–12.PubMedGoogle Scholar
  8. 8.
    Reilly IA, FitzGerald GA. Inhibition of thromboxane formation in vivo and ex vivo: implications for therapy with platelet inhibitory drugs. Blood. 1987;69:180–6.PubMedGoogle Scholar
  9. 9.
    Santilli F, Rocca B, De Cristofaro R, et al. Platelet cyclooxygenase inhibition by low-dose aspirin is not reflected consistently by platelet function assays: implications for aspirin “resistance”. J Am Coll Cardiol. 2009;53:667–77.CrossRefPubMedGoogle Scholar
  10. 10.
    Patrignani P, Filabozzi P, Patrono C. Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects. J Clin Invest. 1982;69:1366–72.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Capone ML, Tacconelli S, Sciulli MG, et al. Clinical pharmacology of platelet, monocyte, and vascular cyclooxygenase inhibition by naproxen and low-dose aspirin in healthy subjects. Circulation. 2004;109:1468–71.CrossRefPubMedGoogle Scholar
  12. 12.
    Shimokawa T, Smith WL. Prostaglandin endoperoxide synthase. The aspirin acetylation region. J Biol Chem. 1992;267:12387–92.PubMedGoogle Scholar
  13. 13.
    Lecomte M, Laneuville O, Ji C, et al. Acetylation of human prostaglandin endoperoxide synthase-2 (cyclooxygenase-2) by aspirin. J Biol Chem. 1994;269:13207–15.PubMedGoogle Scholar
  14. 14.
    Patrono C, Ciabattoni G, Pinca E, et al. Low-dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res. 1980;17:317–27.CrossRefPubMedGoogle Scholar
  15. 15.
    Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994;330:1287–94.CrossRefPubMedGoogle Scholar
  16. 16.
    Pedersen AK, FitzGerald GA. Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase. N Engl J Med. 1984;311:1206–11.CrossRefPubMedGoogle Scholar
  17. 17.
    Bala M, Chin CN, Logan AT, et al. Acetylation of prostaglandin H2 synthases by aspirin is inhibited by redox cycling of the peroxidase. Biochem Pharmacol. 2008;75:1472–81.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Patrono C, Ciabattoni G, Patrignani P, et al. Clinical pharmacology of platelet cyclooxygenase inhibition. Circulation. 1985;72:1177–84.CrossRefPubMedGoogle Scholar
  19. 19.
    McAdam BF, Catella-Lawson F, Mardini IA, et al. Systemic biosynthesis of prostacyclin by cyclooxygenase (COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc Natl Acad Sci U S A. 1999;96:272–7.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    FitzGerald GA, Oates JA, Hawiger J, et al. Endogenous biosynthesis of prostacyclin and thromboxane and platelet function during chronic administration of aspirin in man. J Clin Invest. 1983;71:676–88.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Patrono C, García Rodríguez LA, Landolfi R, et al. Low-dose aspirin for the prevention of atherothrombosis. N Engl J Med. 2005;353:2373–83.CrossRefPubMedGoogle Scholar
  22. 22.
    ATT Collaboration. 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.Google Scholar
  23. 23.
    ATT Collaboration. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet. 2009;373:1849–60.Google Scholar
  24. 24.
    Patrono C. Low-dose aspirin in primary prevention: cardioprotection, chemoprevention, both or neither? Eur Heart J. 2013;34:2403–11.CrossRefGoogle Scholar
  25. 25.
    Thun MJ, Jacobs EJ, Patrono C. The role of aspirin in cancer prevention. Nat Rev Clin Oncol. 2012;9:259–67.CrossRefPubMedGoogle Scholar
  26. 26.
    Patrono C, Baigent C, Hirsh J, et al. Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133:199S–233S.Google Scholar
  27. 27.
    Pierucci A, Simonetti BM, Pecci G, et al. Improvement of renal function with selective thromboxane antagonism in lupus nephritis. N Engl J Med. 1989;320:421–5.CrossRefPubMedGoogle Scholar
  28. 28.
    Hansson L, Zanchetti A, Carruthers S, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomized trial. Lancet. 1998;351:1755–62.CrossRefPubMedGoogle Scholar
  29. 29.
    Brochier ML. Evaluation of flurbiprofen for prevention of reinfarction and reocclusion after successful thrombolysis or angioplasty in acute myocardial infarction. The Flurbiprofen French Trial. Eur Heart J. 1993;14:951–7.CrossRefPubMedGoogle Scholar
  30. 30.
    Garcìa Rodrìguez LA, Varas C, Patrono C. Differential effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs in the primary prevention of myocardial infarction in postmenopausal women. Epidemiology. 2000;11:382–7.CrossRefPubMedGoogle Scholar
  31. 31.
    Kearney PM, Baigent C, Godwin J, et al. Do selective cyclooxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomized trials. BMJ. 2006;332:1302–8.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Catella-Lawson F, Reilly MP, Kapoor SC, et al. Cyclooxygenase inhibitors and the antiplatelet effects of aspirin. N Engl J Med. 2001;345:1809–17.CrossRefPubMedGoogle Scholar
  33. 33.
    Renda G, Tacconelli S, Capone ML, et al. Celecoxib, ibuprofen, and the antiplatelet effect of aspirin in patients with osteoarthritis and ischemic heart disease. Clin Pharmacol Ther. 2006;80:264–74.CrossRefPubMedGoogle Scholar
  34. 34.
    Capone ML, Sciulli MG, Tacconelli S, et al. Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects. J Am Coll Cardiol. 2005;45:1295–301.CrossRefPubMedGoogle Scholar
  35. 35.
    Baigent C, Patrono C. Selective cyclooxygenase 2 inhibitors, aspirin, and cardiovascular disease: a reappraisal. Arthritis Rheum. 2003;48:12–20.CrossRefPubMedGoogle Scholar
  36. 36.
    Grosser T, Fries S, FitzGerald GA. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J Clin Invest. 2006;116:4–15.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Nussmeier NA, Whelton AA, Brown MT, et al. Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery. N Engl J Med. 2005;352:1081–91.CrossRefPubMedGoogle Scholar
  38. 38.
    Furberg CD, Psaty BM, FitzGerald GA. Parecoxib, valdecoxib, and cardiovascular risk. Circulation. 2005;111:249.CrossRefPubMedGoogle Scholar
  39. 39.
    MacDonald TM. Standard care versus celecoxib outcome trial. Presented at the European Society of Cardiology Congress, London 29 August-2 September 2015.Google Scholar
  40. 40.
    Antman EM, Bennett JS, Daugherty A, Furberg C, Roberts H, Taubert KA, et al. Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association. Circulation. 2007;115:1634–42.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of PharmacologyCatholic University School of MedicineRomeItaly

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