Cited by 164Inflammatory mediators and NSAID effectsAntiplatelet Therapy and Cardiovascular DiseasesEicosanoids and Hypertension Pharmacology

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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

Schmidt, Morten, Lamberts, Morten, Olsen, Anne-Marie Schjerning, Fosbøll, Emil, Niessner, Alexander, Tamargo, Juan, Rosano, Giuseppe, Agewall, Stefan, Kaski, Juan Carlos, Kjeldsen, Keld, Lewis, Basil S., Torp-Pedersen, Christian·2016·European Heart Journal

DOI 10.1093/eurheartj/ehv505

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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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See all 164

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: Schmidt, Morten
Lamberts, Morten
Niessner, Alexander
Tamargo, Juan
Rosano, Giuseppe
Agewall, Stefan
Kaski, Juan Carlos
Lewis, Basil S.
Torp-Pedersen, Christian
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
DOI: 10.1093/eurheartj/ehv505
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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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

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