Elsevier

Clinical Therapeutics

Volume 32, Issue 4, April 2010, Pages 667-677
Clinical Therapeutics

Strategies to optimize treatment with NSAIDs in patients at risk for gastrointestinal and cardiovascular adverse events

https://doi.org/10.1016/j.clinthera.2010.04.009Get rights and content

Abstract

Background: NSAIDs, including cyclooxygenase (COX)-2 inhibitors, are among the most widely prescribed medications worldwide. However, NSAIDs have been associated with gastrointestinal (GI) toxicity. The cardiovascular (CV) toxicity associated with COX-2 inhibitors and some other NSAIDs further complicates the choice of therapy.

Objective: The aim of this commentary was to appraise current NSAID treatment strategies and provide clinicians with guidance on the GI and CV risks of these strategies and choosing an appropriate treatment in individual patients.

Methods: A literature search of PubMed was conducted (1989-August 2009) to gather relevant studies, meta-analyses, reviews, and treatment guidelines using the following terms, either alone or in combination: NSAID, gastrointestinal, cardiovascular, toxicity, gastroprotection, proton pump inhibitor, COX-2 inhibitor, aspirin, fixed-dose combination, and adherence.

Results: Based on the data from the literature search, gastroprotective strategies (eg, proton pump inhibitors [PPIs]) are underused in patients at risk for NSAIDrelated GI complications, including in those patients most at risk. Risk factors for GI toxicity with NSAID use include high NSAID dose, a history of NSAID-associated GI adverse events or the presence of upper GI symptoms, advanced age, corticosteroid use, concurrent aspirin use, and certain comorbidities (eg, rheumatoid arthritis). Risk factors for CV toxicity with NSAID use include established CV disease or an estimated 10-year CV risk >20%. Findings from randomized controlled trials have suggested that, in patients with an increased risk for GI complications, the use of a nonselective NSAID with a PPI may be at least as effective as the use of a COX-2 selective inhibitor in preventing the recurrence of ulcer complications. In patients with a high GI risk and a moderate CV risk, the use of a COX-2 inhibitor with a PPI may be appropriate.

Conclusions: The choice of NSAID should be tailored to the GI and CV risks in the patient. The risk profile can be affected by numerous factors, including NSAID dosing and concurrent aspirin use. Thus, individualized risk stratification should be the clinician's primary consideration when selecting treatment.

References (60)

  • WA Ray et al.

    Risk of peptic ulcer hospitalizations in users of NSAIDs with gastroprotective cotherapyversus coxibs

    Gastroenterology

    (2007)
  • FK Chan et al.

    Combination of a cyclo-oxygenase-2 inhibitor and a proton-pump inhibi tor for prevention of recurrent ulcer bleeding in patients at very high risk: A double-blind, randomised trial

    Lancet

    (2007)
  • JL Goldstein et al.

    Ulcer recurrence in high-risk patients receiving non steroidal anti-inflammatory drugs plus low-dose aspirin: Results of a post hoc subanalysis

    Clin Ther

    (2004)
  • JL Goldstein et al.

    Celecoxib plus aspirin versus naproxen and lansoprazole plus aspirin: A randomized, double-blind, endoscopic trial

    Clin Gastroenterol Hepatol

    (2007)
  • RC Becker et al.

    The primary and secondary prevention of coronary artery disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)

    Chest

    (2008)
  • C Cheong et al.

    Patient adherence and reimbursement amount for antidiabetic fixed-dose combination products compared with dual therapy among Texas Medicaid recipients

    Clin Ther

    (2008)
  • KC Jackson et al.

    Adherence with multiplecombination anti hypertensive phar macotherapies in a US managed care database

    Clin Ther

    (2008)
  • R Pounder

    Silent peptic ulceration: Deadly silence or golden silence?

    Gastroenterology

    (1989)
  • S Bangalore et al.

    Fixed-dose combinations improve medication compliance: A meta-analysis

    Am J Med

    (2007)
  • R Paulose-Ram et al.

    Frequent monthly use of selected non-prescription and prescription non-narcotic analgesics among US adults

    Pharmacoepidemiol Drug Saf

    (2005)
  • A Lanas et al.

    Inappropriate prevention of NSAI Dinduced gastrointestinal events among long-term users in the elderly

    Drugs Aging

    (2007)
  • JM Scheiman

    The impact of nonsteroidal anti-inflammatory drug-induced gastropathy

    Am J Manag Care

    (2001)
  • G Singh et al.

    Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. A prospective observational cohort study

    Arch Intern Med

    (1996)
  • MC Sturkenboom et al.

    Underutilization of preventive strategies inpatients receiving NSAIDs

    Rheumatology (Oxford)

    (2003)
  • HE Vonkeman et al.

    Underutilisation of gastroprotective drugs in patients with NSAID-related ulcers

  • MM Wolfe et al.

    Gastrointestinal toxicity of nonsteroidal anti inflammatory drugs

    N Engl J Med

    (1999)
  • FE Silverstein et al.

    Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti inflammatory drugs. A randomized, double-blind, placebocontrolled trial

    Ann Intern Med

    (1995)
  • A Lanas et al.

    A nationwide study of mortality associated with hospital admission due to severe gastrointestinal events and those associated with nonsteroidal anti inflammatory drug use

    Am J Gastroenterol

    (2005)
  • F Catella-Lawson et al.

    Cyclooxygenase inhibitors and the antiplatelet effects of aspirin

    N Engl J Med

    (2001)
  • Cited by (82)

    • Diclofenac induced gastrointestinal and renal toxicity is alleviated by thymoquinone treatment

      2018, Food and Chemical Toxicology
      Citation Excerpt :

      Diclofenac also causes gastrointestinal (GI) damage via systemic inhibition of GI mucosal COX activity and thereby modulating arachidonic acid metabolism (Kanbayashi and Konishi, 2015). Diclofenac inhibits lipoxygenases, decreases the production of leukotrienes, suppresses prostaglandin synthesis and thromboxane-prostanoid receptor signaling (Scheiman and Hindley, 2010). Diclofenac is metabolized to 4-hydroxydiclofenac and other hydroxylated forms in the liver, after conjugation and sulfation, the metabolites are excreted mainly in the urine and bile (Kumar et al., 2002).

    • Upper Gastrointestinal Toxicity Associated With Long-Term Aspirin Therapy: Consequences and Prevention

      2017, Current Problems in Cardiology
      Citation Excerpt :

      These relative risks, which were derived from real-world settings, concur with those from randomized trials,18 and are not mitigated by the use of enteric-coated or buffered aspirin.19,20 Further, many of these bleeding episodes occur without prior symptoms. The adverse effects of aspirin on the GI tract are of sufficient frequency and potential severity that it is important to balance the risks of GI and CVD events when deciding on the advisability of prescribing aspirin to a particular patient.21,22 This is particularly problematic in those at increased CVD risk who have experienced a previous GI bleed.23

    View all citing articles on Scopus
    View full text