Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism

A pilot study

David Jimenez, Rosa Nieto, Jesús Corres, Covadonga Fernández-Golfín, Deisy Barrios, Raquel Morillo, Carlos Andres Quezada, Menno Huisman, Roger D. Yusen, Jeffrey Kline

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01590342.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalThrombosis Research
Volume162
DOIs
StatePublished - Feb 1 2018

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Right Ventricular Dysfunction
Diclofenac
Pulmonary Embolism
Placebos
Confidence Intervals
Random Allocation
Hemorrhage
Blood Pressure
Intention to Treat Analysis
Vitamin K
Low Molecular Weight Heparin
Pulmonary Artery
Heart Ventricles
Anti-Inflammatory Agents
Clinical Trials
Safety

ASJC Scopus subject areas

  • Hematology

Cite this

Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism : A pilot study. / Jimenez, David; Nieto, Rosa; Corres, Jesús; Fernández-Golfín, Covadonga; Barrios, Deisy; Morillo, Raquel; Quezada, Carlos Andres; Huisman, Menno; Yusen, Roger D.; Kline, Jeffrey.

In: Thrombosis Research, Vol. 162, 01.02.2018, p. 1-6.

Research output: Contribution to journalArticle

Jimenez, D, Nieto, R, Corres, J, Fernández-Golfín, C, Barrios, D, Morillo, R, Quezada, CA, Huisman, M, Yusen, RD & Kline, J 2018, 'Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism: A pilot study', Thrombosis Research, vol. 162, pp. 1-6. https://doi.org/10.1016/j.thromres.2017.12.002
Jimenez, David ; Nieto, Rosa ; Corres, Jesús ; Fernández-Golfín, Covadonga ; Barrios, Deisy ; Morillo, Raquel ; Quezada, Carlos Andres ; Huisman, Menno ; Yusen, Roger D. ; Kline, Jeffrey. / Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism : A pilot study. In: Thrombosis Research. 2018 ; Vol. 162. pp. 1-6.
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abstract = "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. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01590342.",
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T1 - Diclofenac for reversal of right ventricular dysfunction in acute normotensive pulmonary embolism

T2 - A pilot study

AU - Jimenez, David

AU - Nieto, Rosa

AU - Corres, Jesús

AU - Fernández-Golfín, Covadonga

AU - Barrios, Deisy

AU - Morillo, Raquel

AU - Quezada, Carlos Andres

AU - Huisman, Menno

AU - Yusen, Roger D.

AU - Kline, Jeffrey

PY - 2018/2/1

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N2 - 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. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01590342.

AB - 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. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01590342.

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