Cardiovascular Risk of Nonsteroidal Anti‐inflammatory Drugs and Classical and Selective Cyclooxygenase‐2 Inhibitors: A Meta‐analysis of Observational Studies

Arias, Luis H. Martín; González, Antonio Martín; Fadrique, Rosario Sanz; Salgueiro, Esther

doi:10.1002/jcph.1302

Cited by 48 publications

(32 citation statements)

References 109 publications

(214 reference statements)

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“…Benzodiazepines and opioids are frequently used in the pre- and postoperative stage and of undisputed benefit for anxiety and pain relief, yet they should be stopped as soon as possible because of their large potential to induce falls and therefore their impact on mortality [26–28]. Numerous studies on NSAIDs show their negative impact on cardiovascular system and the increased risk for major bleedings, despite intake of proton-pump inhibitors [29, 30]. They appeared to be the major proportion of PIMs detected in both CTC- and OGC-treated patients, which also might be associated with their beneficial effect, i.e., for the prophylaxis of periarticular ossification in hip fracture patients.…”

Section: Discussionmentioning

confidence: 99%

Orthogeriatric treatment reduces potential inappropriate medication in older trauma patients: a retrospective, dual-center study comparing conventional trauma care and co-managed treatment

et al. 2019

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BackgroundMultimorbidity and polypharmacy are common challenges in the treatment of older trauma patients. Therefore, various integrated care models were developed over the last few years, merging the expertise of geriatricians and trauma surgeons. The aim of this study was to evaluate, if the number of prescriptions of potentially inappropriate medication (PIM) could be reduced in these patients by an interdisciplinary co-managed concept compared to conventional trauma care.MethodsWe conducted a retrospective, dual-center cohort study, including all patients aged 70 years and older admitted with a fracture of the hip or the proximal humerus within the study period. Patients were treated in the universities department of trauma surgery with two different hospital sites, one with conventional trauma care (CTC) and the other one with a certified orthogeriatric trauma unit (OGC). Based on the STOPP/START criteria by O´Mahony et al., PIMs were defined, which should be avoided in (ortho)geriatric patients. Medical records of each patient were analyzed at discharge. Besides patients basic information, all prescribed drugs, changes in the medication plan and who carried out these changes were collected. For statistical analysis based on the data quality and distribution, the t test, Mann–Whitney U test and the Chi-square test were used.ResultsA total of 95 patients were included, 73 of them females, with an average age of 82.59 years (SD ± 6.96). Mean length of hospital stay was 12.98 at CTC and 13.36 days at OGC (p = 0.536). Among conventional care (41 patients), prescription of one or more PIMs was found in 85.4% of the patients, whereas at the orthogeriatric ward (54 patients) only in 22.2% (p < 0.001). Besides that, changes in medication were made for 48.1% of the patients during their stay on the orthogeriatric ward.ConclusionsOur findings show that an integrated care concept can reduce the number of prescriptions of PIMs significantly and potentially avoids adverse drug reactions and additional burdens in older trauma patients.

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Section: Discussionmentioning

confidence: 99%

Orthogeriatric treatment reduces potential inappropriate medication in older trauma patients: a retrospective, dual-center study comparing conventional trauma care and co-managed treatment

et al. 2019

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“…In this work, we aimed to describe the effects of diclofenac (DIC) and naproxen (NAP) on the permeability and structure of lipid bilayers, used as simple model systems of cell and mitochondrial membranes. The rational beyond this study was based on the following points: (a) DIC and NAP ( Figure 1) were chosen because they belong to the higher and lower risk groups (respectively) of NSAIDs to induce cardiotoxicity [12], (b) beyond cell membranes, mitochondrial membranes are of particular interest due to the high density of mitochondria existing in cardiomyocytes, which is crucial to maintain cardiac function; (c) cell death in the myocardium may occur due to alterations in the structure of both inner and outer mitochondria membranes [21]. Therefore, NSAIDs-lipid interactions were evaluated using 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC):cholesterol (80:20) as a model system of cell membranes, POPC:cardiolipin (85:15) as model system of the inner mitochondrial membrane, and POPC:phosphatidylinositol (85:15) as model system of the outer mitochondrial membrane.…”

Section: Of 12mentioning

confidence: 99%

Unraveling the Role of Drug-Lipid Interactions in NSAIDs-Induced Cardiotoxicity

Pereira-Leite¹,

Figueiredo²,

Burdach³

et al. 2020

Membranes

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Cardiovascular (CV) toxicity is nowadays recognized as a class effect of non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs). However, their mechanisms of cardiotoxicity are not yet well understood, since different compounds with similar action mechanisms exhibit distinct cardiotoxicity. For instance, diclofenac (DIC) is among the most cardiotoxic compounds, while naproxen (NAP) is associated with low CV risk. In this sense, this study aimed to unravel the role of drug-lipid interactions in NSAIDs-induced cardiotoxicity. For that, DIC and NAP interactions with lipid bilayers as model systems of cell and mitochondrial membranes were characterized by derivative spectrophotometry, fluorometric leakage assays, and synchrotron X-ray scattering. Both DIC and NAP were found to have the ability to permeabilize the membrane models, as well as to alter the bilayers’ structure. The NSAIDs-induced modifications were dependent on the lipid composition of the membrane model, the three-dimensional structure of the drug, as well as the drug:lipid molar ratio tested. Altogether, this work supports the hypothesis that NSAIDs-lipid interactions, in particular at the mitochondrial level, may be another key step among the mechanisms underlying NSAIDs-induced cardiotoxicity.

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“…Neither celecoxib nor etoricoxib differed significantly from diclofenac in major vascular events (Table 4) [11]. In another meta-analysis of 31 randomized trials (116,429 patients) assessing CV risk (Antiplatelet Trialists' Collaboration composite outcome) versus placebo, both celecoxib and etoricoxib were also comparable to diclofenac and other NSAIDs [54]—a result supported by the largest meta-analysis of observational data (Table 4) [55, 56]. In most of these meta-analyses, a mixture of direct and indirect comparisons was used to draw the conclusions, as there are no direct data comparing the CV safety of celecoxib and etoricoxib.…”

Section: Comparison Of Safety Profiles Of Celecoxib Etoricoxib Amentioning

confidence: 92%

Are All Oral COX-2 Selective Inhibitors the Same? A Consideration of Celecoxib, Etoricoxib, and Diclofenac

Walker

2018

International Journal of Rheumatology

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Nonsteroidal anti-inflammatory drugs (NSAIDs) have been widely used for the treatment of arthritic conditions. Drugs in this heterogeneous class alleviate pain and inflammation by inhibiting cyclooxygenase-2 (COX-2). Cyclooxygenase-1 (COX-1) inhibition has traditionally been associated with increased gastrointestinal (GI) harm, whereas increased COX-2 selectivity has more recently become associated with greater risk of cardiovascular (CV) harm. When the entirety of data is considered, NSAIDs can be seen to exhibit a range of COX isoform selectivity, with all oral NSAIDs appearing to be associated with an increase in CV events. This review focuses on a comparison of the efficacy and the GI and CV safety profiles of three commonly used NSAIDs—celecoxib, etoricoxib, and diclofenac—using direct comparisons where available. While all three treatments are shown to have comparable efficacy, there are differences in their safety profiles. Both celecoxib and etoricoxib are associated with less GI harm than diclofenac despite the similarity of its COX-2 selectivity to celecoxib. Each of the three medicines under consideration is associated with a similar overall risk of CV events (fatal and nonfatal heart attacks and strokes). However, there are consistent differences in effects on blood pressure (BP), reported both from trials using ambulatory techniques and from meta-analyses of randomized trials, reporting investigator determined effects, with etoricoxib being associated with a greater propensity to destabilize BP control than either diclofenac or celecoxib.

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Cardiovascular Risk of Nonsteroidal Anti‐inflammatory Drugs and Classical and Selective Cyclooxygenase‐2 Inhibitors: A Meta‐analysis of Observational Studies

Cited by 48 publications

References 109 publications

Orthogeriatric treatment reduces potential inappropriate medication in older trauma patients: a retrospective, dual-center study comparing conventional trauma care and co-managed treatment

Orthogeriatric treatment reduces potential inappropriate medication in older trauma patients: a retrospective, dual-center study comparing conventional trauma care and co-managed treatment

Unraveling the Role of Drug-Lipid Interactions in NSAIDs-Induced Cardiotoxicity

Are All Oral COX-2 Selective Inhibitors the Same? A Consideration of Celecoxib, Etoricoxib, and Diclofenac

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