Eficacia de diclofenaco en pacientes con tromboembolia de pulmón submasivaensayo clínico aleatorizado

Abstract

Background: In patients with acute pulmonary embolism (PE), the inflammatory response might contribute to the development of right ventricular (RV) dysfunction. This double blind, randomized, controlled trial investigated whether diclofenac is superior to anticoagulation alone in the reversal of RV dysfunction in intermediaterisk patients. Methods: We randomly assigned 34 normotensive patients with acute PE and echocardiographic RV dysfunction to receive diclofenac (two doses of 75 mg in the first 24 hours after diagnosis) plus heparin (diclofenac group) or placebo plus heparin (heparin group). Right ventricular dysfunction was defined by the presence of, at least, two of the following criteria: i) diastolic diameter of the right ventricle > 30 mm in the parasternal window; ii) diameter of the right ventricle greater than that of the left ventricle in the apical or subcostal space; iii) hypokinesis of the right ventricular free wall; and iv) pulmonary systolic pressure > 30 mm Hg. The primary efficacy outcome was persistence of RV dysfunction 48 hours after initiation of treatment. The secondary efficacy outcome was persistence of RV dysfunction 7 days after initiation of treatment. The primary safety outcome was major bleeding within 7 days after initiation of treatment. Results: Thirty-four patients were randomly assigned to diclofenac (17) or placebo (17). In intention-to-treat analyses, rates of persistent RV dysfunction at 48 hours were 59% (95% confidence interval [CI], 33-82%) in the diclofenac group and 76% (95% CI, 50-93%) in the placebo group (difference in risk [diclofenac minus standard anticoagulation], -17 percentage points; 95% CI, -47 to 17). By day 7, diclofenac and placebo groups were associated with similar RV dysfunction rates (35% in both arms). Major bleeding occurred in none of patients in the diclofenac group and in 5.9% of patient in the heparin group. Rates of other adverse events were similar in the two groups. Conclusions: Our study is inconclusive as to a potential benefit of diclofenac over placebo to reverse RV dysfunction in patients with pulmonary embolism at intermediate risk.