Browsing by Subject "Diclofenac"

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    Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism: A pilot study
    (Elsevier, 2018-02) Jimenez, David; Nieto, Rosa; Corres, Jesús; Fernández-Golfín, Covadonga; Barrios, Deisy; Morillo, Raquel; Quezada, Carlos Andres; Huisman, Menno; Yusen, Roger D.; Kline, Jeffrey A.; Emergency Medicine, School of Medicine
    Background The inflammatory response associated with acute pulmonary embolism (PE) contributes to the development of right ventricular (RV) dysfunction. Nonsteroidal anti-inflammatory drugs (NSAIDs) may facilitate the reversal of PE-associated RV dysfunction. Methods We randomly assigned normotensive patients who had acute PE associated with echocardiographic RV dysfunction and normal systemic blood pressure to receive intravenous (IV) diclofenac (two doses of 75 mg in the first 24 h after diagnosis) or IV placebo. All patients received standard anticoagulation with subcutaneous low-molecular-weight heparin (LMWH) and an oral vitamin K antagonist. RV dysfunction was defined by the presence of, at least, two of the following criteria: i) RV diastolic diameter > 30 mm in the parasternal window; ii) RV diameter > left ventricle diameter in the apical or subcostal space; iii) RV free wall hypokinesis; and iv) estimated pulmonary artery systolic pressure > 30 mm Hg. Persistence of RV dysfunction at 48 h and 7 days after randomization were the primary and secondary efficacy outcomes, respectively. The primary safety outcome was major bleeding within 7 days after randomization. Results Of the 34 patients randomly assigned to diclofenac or placebo, the intention-to-treat analysis showed persistent RV dysfunction at 48 h in 59% (95% confidence interval [CI], 33–82%) of the diclofenac group and in 76% (95% CI, 50–93%) of the placebo group (difference in risk [diclofenac minus standard anticoagulation], − 17 percentage points; 95% CI, − 47 to 17). Similar proportions (35%) of patients in the diclofenac and placebo groups had persistent RV dysfunction at 7 days. Major bleeding occurred in none of patients in the diclofenac group and in 5.9% (95% CI, 0.2–29%) of patient in the placebo group. Conclusions Due to slow recruitment, our study is inconclusive as to a potential benefit of diclofenac over placebo to reverse RV dysfunction in normotensive patients with acute PE.
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    Drug-Induced Liver Injury [DILI] ascribed to Non-steroidal Anti-inflammatory Drugs [NSAIDs] in the USA— Update with Genetic Correlations
    (Wiley, 2024) Bonkovsky, Herbert L.; Ghabril, Marwan; Nicoletti, Paola; Dellinger, Andrew; Fontana, Robert J.; Barnhart, Huiman; Gu, Jiezhun; Daly, Ann K.; Aithal, Guruprasad P.; Phillips, Elizabeth J.; Kleiner, David E.; US DILIN Investigators; Medicine, School of Medicine
    Objective: To describe patients with NSAID-DILI, including genetic factors associated with idiosyncratic DILI. Methods: In DILIN, subjects with presumed DILI are enrolled and followed for at least 6 months. Causality is adjudicated by a Delphic approach. HLA sequencing of multiethnic NSAID-DILI patients and HLA allele imputation of matching population controls were performed following overall, class and drug-based association analysis. Significant results were tested in a non-Hispanic White (NHW) case-control replication cohort. Results: Between September 2004 and March 2022, causality was adjudicated in 2498, and 55 (41 [75%] women) were assessed as likely due to NSAIDs. Median age at onset was 55 y (range 22-83 y). Diclofenac was the causative drug in 29, celecoxib in 7, ibuprofen in 5, etodolac and meloxicam each in 4. Except for meloxicam and oxaprozin (n = 2), the liver injury was hepatocellular with median R 15-25. HLA-DRB1*04:03 and HLA-B*35:03 were significantly more frequent in NSAID-DILI patients than in non-NSAID DILI controls. Interestingly, 85% of the HLA-DRB1*04:03 carriers developed DILI due to the use of acetic acid derivative NSAIDs, supporting the hypothesis that HLA-DRB1*04:03 could be a drug and/or class risk factor. HLA-B*35:03 but not HLA-DRB1*04:03 association was confirmed in the independent NHW replication cohort, which was largely driven by diclofenac. Conclusions: Despite prevalent use, NSAID-DILI is infrequent in the United States. Diclofenac is the most commonly implicated, and adherence to warnings of risk and close observation are recommended. The increased frequency of HLA-B*35:03 and DRB1*04:03, driven by diclofenac, suggests the importance of immune-mediated responses.