The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
Cardiovascular safety of non-aspirin non-steroidal anti-inflammatory drugs: review and position paper by the working group for Cardiovascular Pharmacotherapy of the European Society of Cardiology
Abstract
Non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) have been used in clinical practice for more than a century and are among the most widely used drugs worldwide for the treatment of pain, fever, and inflammation.1,2 For decades, it has been known that many of these drugs can cause fluid retention and elevate blood pressure,3 thus increasing cardiovascular risk particularly in heart failure patients.4 However, the main worry in relation to the use of these agents has been gastrointestinal bleeding.5 Newer selective COX-2 inhibitors (coxibs) were developed as NSAIDs with reduced gastrointestinal toxicity, but retained analgesic and anti-inflammatory properties. Coxibs were tested in accordance to modern drug development regulations with large numbers of patients included in clinical trials. These trials demonstrated that rofecoxib,6–8 celecoxib,9 valdecoxib,10 and parecoxib10 increased the risk of cardiovascular complications. As a result, coxibs currently have very limited indications for use. Paradoxically, an older and relatively selective COX-2 inhibitor, diclofenac,11 continues to be one of the most widely used drugs worldwide and is in most countries sold over the counter.1 Mixed COX-1/COX-2 inhibitors such as ibuprofen and naproxen are also used widely and, without solid evidence, assumed to be safe. Given the current uncertainty regarding the safety of this class of agents and the rapidly accumulating data on their cardiovascular risks, this review summarizes the current evidence from randomized and observational studies on the cardiovascular safety of non-aspirin NSAIDs and presents a position for their use. Non-steroidal anti-inflammatory drugs exhibit their anti-inflammatory effect by inhibiting COX, which is the rate-limiting enzyme in prostaglandin synthesis ( Figure 1 ).12 There are …
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“Conversely, non‐steroidal anti‐inflammatory drugs can increase the risk of progression of CHF as well as the frequency of adverse events, making its use controversial. 90”
From Prioritizing symptom management in the treatment of chronic heart failure (2020) · cites this paper as [90]
Citations
Cites
Collaboration, A. T. (2002) · BMJ · doi:10.1136/bmj.324.7329.71 · Cited by 6,943
Bombardier, C., Laine, L., Reicin, A. S., Shapiro, D., Burgos‐Vargas, R., Davis, B. R., Day, R. O., Ferraz, M. B., Hawkey, C. J., Hochberg, M. C., et al. (2000) · New England Journal of Medicine · doi:10.1056/nejm200011233432103 · Cited by 4,014
Silverstein, F. E., Faich, G. A., Goldstein, J. L., Simon, L. S., Pincus, T., Whelton, A., Makuch, R., Eisen, G. M., Agrawal, N. M., Stenson, W. F., et al. (2000) · JAMA · doi:10.1001/jama.284.10.1247 · Cited by 3,144
Cardiovascular Events Associated with Rofecoxib in a Colorectal Adenoma Chemoprevention Trial
Bresalier, R. S., Sandler, R. S., Quan, H., Bolognese, J. A., Oxenius, B., Horgan, K., Lines, C., Riddell, R., Morton, D., Lanas, A., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050493 · Cited by 2,519
Cardiovascular Risk Associated with Celecoxib in a Clinical Trial for Colorectal Adenoma Prevention
Solomon, S. D., McMurray, J. J. V., Pfeffer, M. A., Wittes, J. T., Fowler, R. A., Finn, P. V., Anderson, W. F., Zauber, A. G., Hawk, E. T., & Bertagnolli, M. M. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050405 · Cited by 2,041
Risk of Cardiovascular Events Associated with Selective COX-2 Inhibitors
Mukherjee, D. (2001) · JAMA · doi:10.1001/jama.286.8.954 · Cited by 1,741
The Coxibs, Selective Inhibitors of Cyclooxygenase-2
FitzGerald, G. A., & Patrono, C. (2001) · New England Journal of Medicine · doi:10.1056/nejm200108093450607 · Cited by 1,572
Kearney, P. M., Baigent, C., Godwin, J., Halls, H. J., Emberson, J., & Patrono, C. (2006) · BMJ · doi:10.1136/bmj.332.7553.1302 · Cited by 1,440
Cyclooxygenase Inhibitors and the Antiplatelet Effects of Aspirin
Catella-Lawson, F., Reilly, M. P., Kapoor, S. C., Cucchiara, A. J., DeMarco, S., Tournier, B., Vyas, S. N., & FitzGerald, G. A. (2001) · New England Journal of Medicine · doi:10.1056/nejmoa003199 · Cited by 1,394
Research works printed but not linked: 3
- European Medicines Agency, 2006, Public CHMP assessment report for medicinal products containing non-selective non-steroidal anti-inflammatory drugs (NSAIDs)
- European Medicines Agency, 2012, Assessment report for non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk
- Oxford Centre for Evidence-based Medicine, Levels of Evidence (March 2009)
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Sorted by citations
Halvorsen, S., Mehilli, J., Cassese, S., Hall, T. S., Abdelhamid, M., Barbato, E., Hert, S. G. D., de Laval, I., Geisler, T., Hinterbuchner, L., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac270 · Cited by 1,287
Rao, S. V., O’Donoghue, M. L., Ruel, M., Rab, T., Tamis-Holland, J. E., Alexander, J. H., Baber, U., Baker, H., Cohen, M. G., Cruz-Ruiz, M., et al. (2025) · Circulation · doi:10.1161/cir.0000000000001309 · Cited by 625
2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes
Rao, S. V., O’Donoghue, M. L., Ruel, M., Rab, T., Tamis-Holland, J. E., Alexander, J. H., Baber, U., Baker, H., Cohen, M. G., Cruz-Ruiz, M., et al. (2025) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2024.11.009 · Cited by 668
Cardiovascular effects and safety of (non-aspirin) NSAIDs
Schjerning, A.-M., McGettigan, P., & Gislason, G. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-0366-z · Cited by 387
Anti‐inflammatory therapies in myocardial infarction: failures, hopes and challenges
Huang, S., & Frangogiannis, N. G. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14155 · Cited by 283
Metadata
- Authors
- Schmidt, M., Lamberts, M., Olsen, A.-M. S., Fosbøll, E., Niessner, A., Tamargo, J., Rosano, G., Agewall, S., Kaski, J. C., Kjeldsen, K., Lewis, B. S., & Torp-Pedersen, C.
- Affiliations
- Aarhus University Hospital (DK)
- Gentofte Hospital (DK)
- The Heart Centre, Copenhagen University Hospital Rigshospitalet 3 Department of Cardiology , , Copenhagen,
- Medical University of Vienna (AT)
- Universidad Complutense de Madrid (ES)
- St George's Hospital (GB)
- Oslo University Hospital (NO)
- St George's, University of London (GB)
- University of Copenhagen (DK)
- Technion – Israel Institute of Technology (IL)
- Aalborg University (DK)
- Corresponding author
- Schmidt, Morten
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-03-16
- Volume
- 37
- Issue
- 13
- Pages
- 1015-1023
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2298123402
- Cited by
- 164
- References
- 83
- Citations by year
- 2026: 11 · 2025: 13 · 2024: 9 · 2023: 14 · 2022: 21 · 2021: 13 · 2020: 16 · 2019: 24 · 2018: 18 · 2017: 17 · 2016: 6
- FWCI
- 17.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Scopus (Elsevier) (submittedVersion)
- VBN Forskningsportal (Aalborg Universitet) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- cardiovascular safety, cardiovascular risk, COX-2 inhibitors, rofecoxib, celecoxib, valdecoxib, parecoxib, diclofenac, ibuprofen, naproxen, gastrointestinal bleeding, heart failure, fluid retention, elevated blood pressure, cyclooxygenase inhibition, prostaglandin synthesis
- MeSH terms
- Anti-Inflammatory Agents, Non-Steroidal, Atrial Fibrillation, Cardiovascular Diseases, Drug Therapy, Combination, Fibrinolytic Agents, Heart Failure, Hemostasis, Humans, Intraoperative Complications, Myocardial Infarction, Public Health, Risk Factors, Randomized Controlled Trials as Topic, Cyclooxygenase Inhibitors, Drug Approval, Risk Assessment, Safety-Based Drug Withdrawals, Observational Studies as Topic
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