Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism: A pilot study

• Published in: Thrombosis research 2018-02, Vol.162, p.1-6
• Main Authors: Jimenez, David, Nieto, Rosa, Corres, Jesús, Fernández-Golfín, Covadonga, Barrios, Deisy, Morillo, Raquel, Quezada, Carlos Andres, Huisman, Menno, Yusen, Roger D., Kline, Jeffrey
• Format: Article
• Language: English
• Subjects: Aged; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Diclofenac - pharmacology; Diclofenac - therapeutic use; Female; Humans; Male; Pilot Projects; Pulmonary Embolism - drug therapy; Pulmonary Embolism - pathology; Ventricular Dysfunction, Right - drug therapy; Ventricular Dysfunction, Right - pathology
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2017.12.002

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. 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 75mg in the first 24h 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>30mm 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>30mmHg. Persistence of RV dysfunction at 48h and 7days after randomization were the primary and secondary efficacy outcomes, respectively. The primary safety outcome was major bleeding within 7days after randomization. Of the 34 patients randomly assigned to diclofenac or placebo, the intention-to-treat analysis showed persistent RV dysfunction at 48h 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 7days. 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. 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. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01590342. •Anti-inflammatory drugs may facilitate the reversal of RV dysfunction in PE.•We assessed the efficacy of diclofenac for reversing RV dysfunction in PE.•Our study is inconclusive as to a potential benefit of diclofenac in PE.