Abstract
Background
There is limited information about the safety of chronic nonsteroidal anti-inflammatory
drugs (NSAIDs) in hypertensive patients with coronary artery disease.
Methods
This was a post hoc analysis from the INternational VErapamil Trandolapril STudy (INVEST),
which enrolled patients with hypertension and coronary artery disease. At each visit,
patients were asked by the local site investigator if they were currently taking NSAIDs.
Patients who reported NSAID use at every visit were defined as chronic NSAID users,
while all others (occasional or never users) were defined as nonchronic NSAID users.
The primary composite outcome was all-cause death, nonfatal myocardial infarction,
or nonfatal stroke. Cox regression was used to construct a multivariate analysis for
the primary outcome.
Results
There were 882 chronic NSAID users and 21,694 nonchronic NSAID users (n = 14,408 for
never users and n=7286 for intermittent users). At a mean follow-up of 2.7 years, the primary outcome
occurred at a rate of 4.4 events per 100 patient-years in the chronic NSAID group,
versus 3.7 events per 100 patient-years in the nonchronic NSAID group (adjusted hazard
ratio [HR] 1.47; 95% confidence interval [CI], 1.19-1.82; P=.0003). This was due to an increase in cardiovascular mortality (adjusted HR 2.26;
95% CI, 1.70-3.01; P<.0001).
Conclusion
Among hypertensive patients with coronary artery disease, chronic self-reported use
of NSAIDs was associated with an increased risk of adverse events during long-term
follow-up.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The American Journal of MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.N Engl J Med. 2000; 343: 1520-1528
- Cardiovascular events associated with rofecoxib in a colorectal adenoma chemoprevention trial.N Engl J Med. 2005; 352: 1092-1102
- Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention.N Engl J Med. 2005; 352: 1071-1080
- Risk of cardiovascular events and rofecoxib: cumulative meta-analysis.Lancet. 2004; 364: 2021-2029
- Cardiovascular risk of celecoxib in 6 randomized placebo-controlled trials: the cross trial safety analysis.Circulation. 2008; 117: 2104-2113
- Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis?.BMJ. 2006; 332: 1302-1308
- Use of nonsteroidal antiinflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association.Circulation. 2007; 115: 1634-1642
- Nonselective nonsteroidal antiinflammatory drugs and cardiovascular risk: are they safe?.Ann Pharmacother. 2007; 41: 1163-1173
- 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
- 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
- Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals.Circ Cardiovasc Qual Outcomes. 2010; 3: 395-405
- 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
- Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis.BMJ. 2011; 342: c7086
- Cognitive function over time in the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT): results of a randomized, controlled trial of naproxen and celecoxib.Arch Neurol. 2008; 65: 896-905
- 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
- Risk of death or reinfarction associated with the use of selective cyclooxygenase-2 inhibitors and nonselective nonsteroidal antiinflammatory drugs after acute myocardial infarction.Circulation. 2006; 113: 2906-2913
- Effect of ibuprofen on cardioprotective effect of aspirin.Lancet. 2003; 361: 573-574
- Aspirin, ibuprofen, and mortality after myocardial infarction: retrospective cohort study.BMJ. 2003; 327: 1322-1323
- A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease.JAMA. 2003; 290: 2805-2816
- Rationale, design, and governance of Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION), a cardiovascular end point trial of nonsteroidal antiinflammatory agents in patients with arthritis.Am Heart J. 2009; 157: 606-612
- Pharmacological management of persistent pain in older persons.J Am Geriatr Soc. 2009; 57: 1331-1346
- Do nonsteroidal anti-inflammatory drugs affect blood pressure?.Ann Intern Med. 1994; 121: 289-300
- Systematic review of trials of the effect of continued use of oral non-selective NSAIDs on blood pressure and hypertension.Curr Med Res Opin. 2007; 23: 2395-2404
- Inhibition of clinical benefits of aspirin on first myocardial infarction by nonsteroidal antiinflammatory drugs.Circulation. 2003; 108: 1191-1195
- Cyclooxygenase inhibitors and the antiplatelet effects of aspirin.N Engl J Med. 2001; 345: 1809-1817
- Pharmacodynamic interaction of naproxen with low-dose aspirin in healthy subjects.J Am Coll Cardiol. 2005; 45: 1295-1301
- Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs.N Engl J Med. 1999; 340: 1888-1899
- Nonsteroidal anti-inflammatory drugs and gastrointestinal disease: pathophysiology, treatment and prevention.Dig Dis. 1995; 13: 119-129
- Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events.Circulation. 2006; 113: 1578-1587
- Coronary artery disease and rheumatoid arthritis.Curr Opin Rheumatol. 2002; 14: 115-120
- Prevalence of cardiovascular disease risk factors among US adults with self-reported osteoarthritis: data from the Third National Health and Nutrition Examination Survey.Am J Manag Care. 2002; 8: S383-S391
- Increased prevalence of metabolic syndrome in individuals with osteoarthritis: an analysis of NHANES III data.Postgrad Med. 2009; 121: 9-20
- Osteoarthritis: another component of metabolic syndrome?.Metab Syndr Relat Disord. 2010; 8: 295-305
- Obesity paradox in patients with hypertension and coronary artery disease.Am J Med. 2007; 120: 863-870
- Hypercholesterolemia paradox in relation to mortality in acute coronary syndrome.Clin Cardiol. 2009; 32: E22-E28
Article info
Publication history
Published online: May 19, 2011
Footnotes
Funding: INVEST was funded by a grant from Abbott Laboratories and the University of Florida Opportunity Fund.
Conflict of Interest: Drs. Bavry, Khaliq, and Gong have no financial disclosures. Dr. Handberg received grant support from the National Institutes of Health (NIH) (National Heart, Lung and Blood Institute [NHLBI]), Abbott Laboratories, Fujisawa, Pfizer, and GlaxoSmithKline. Dr. Cooper-DeHoff received research funding from Abbott Laboratories during the conduct of INVEST and is currently receiving funding from NIH (NHLBI) K23HL086558. Dr. Pepine received research grants from NIH (NHLBI), Baxter, Pfizer, GlaxoSmithKline, and Bioheart, Inc. and is a consultant for Abbott Laboratories, Forest Laboratories, Novartis/Cleveland Clinic, NicOx, Angioblast, Sanofi-Aventis, NHLBI, NIH, Medtelligence, and SLACK Inc. Drs. Handberg and Pepine have received educational grants from the Vascular Biology Working Group (AstraZeneca, Sanofi-Aventis, Schering-Plough, Daiichi-Sankyo Lilly, AtCor Medical, and XOMA).
Authorship: This work is original, and all authors significantly contributed to this paper and accept responsibility for its scientific content.
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
ScienceDirect
Access this article on ScienceDirectLinked Article
- Aspirin and the Harmful Effect of NSAIDsThe American Journal of MedicineVol. 125Issue 2
- PreviewThe article by Bavry et al1 reporting the recurrence of myocardial infarction after the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with established cardiovascular disease is of great interest and of relevance for clinicians working in the “real world.” Although the mechanism for the harmful effect of NSAIDs remains poorly understood, it is feasible that NSAIDs would induce an imbalance between cyclooxygenase-2 (COX-2)-derived prostacyclin (PGI2) and the COX-1-derived thromboxane (TXA2).
- Full-Text
- Preview
