Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes in Patients Hospitalized for COPD Exacerbation: A Randomized Clinical Trial

Abstract

Importance: Active search for pulmonary embolism (PE) may improve outcomes in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD).

Objective: To compare usual care plus an active strategy for diagnosing PE with usual care alone in patients hospitalized for COPD exacerbation.

Design, setting, and participants: Randomized clinical trial conducted across 18 hospitals in Spain. A total of 746 patients were randomized from September 2014 to July 2020 (final follow-up was November 2020).

Interventions: Usual care plus an active strategy for diagnosing PE (D-dimer testing and, if positive, computed tomography pulmonary angiogram) (n = 370) vs usual care (n = 367).

Main outcomes and measures: The primary outcome was a composite of nonfatal symptomatic venous thromboembolism (VTE), readmission for COPD, or death within 90 days after randomization. There were 4 secondary outcomes, including nonfatal new or recurrent VTE, readmission for COPD, and death from any cause within 90 days. Adverse events were also collected.

Results: Among the 746 patients who were randomized, 737 (98.8%) completed the trial (mean age, 70 years; 195 [26%] women). The primary outcome occurred in 110 patients (29.7%) in the intervention group and 107 patients (29.2%) in the control group (absolute risk difference, 0.5% [95% CI, -6.2% to 7.3%]; relative risk, 1.02 [95% CI, 0.82-1.28]; P = .86). Nonfatal new or recurrent VTE was not significantly different in the 2 groups (0.5% vs 2.5%; risk difference, -2.0% [95% CI, -4.3% to 0.1%]). By day 90, a total of 94 patients (25.4%) in the intervention group and 84 (22.9%) in the control group had been readmitted for exacerbation of COPD (risk difference, 2.5% [95% CI, -3.9% to 8.9%]). Death from any cause occurred in 23 patients (6.2%) in the intervention group and 29 (7.9%) in the control group (risk difference, -1.7% [95% CI, -5.7% to 2.3%]). Major bleeding occurred in 3 patients (0.8%) in the intervention group and 3 patients (0.8%) in the control group (risk difference, 0% [95% CI, -1.9% to 1.8%]; P = .99).

Conclusions and relevance: Among patients hospitalized for an exacerbation of COPD, the addition of an active strategy for the diagnosis of PE to usual care, compared with usual care alone, did not significantly improve a composite health outcome. The study may not have had adequate power to assess individual components of the composite outcome.

Trial registration: ClinicalTrials.gov Identifier: NCT02238639.

Conflict of interest statement

Conflict of Interest Disclosures: Dr D. Jimenez reported receiving personal fees from Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Leo Pharma, and Pfizer and grants from Daiichi Sankyo, Rovi, and Sanofi outside the submitted work. Dr Agusti reported receiving grants and personal fees from AstraZeneca, GlaxoSmithKline, and Menarini and personal fees from Chiesi outside the submitted work. Dr Jara-Palomares reported receiving grants from Leo Pharma and MSD and personal fees from Daichii, Rovi, GlaxoSmithKline, and Actellion outside the submitted work. Dr Ruiz-Artacho reported receiving personal fees from Bristol Myers Squibb, Leo Pharma, and Daiichi Sankyo and grants from ROVI outside the submitted work. Dr Calle Rubio reported receiving personal fees from Boehringer Ingelheim, AstraZeneca, Menarini, Novartis, Grifols, and GlaxoSmithKline and consulting fees from GlaxoSmithKline, Gebro Pharma, and Novartis during the conduct of the study. Dr Bertoletti reported receiving personal fees from board, symposia, and congress travel from Actelion, Aspen, Bayer, Bristol Myers Squibb/Pfizer, Leo Pharma, and MSD and travel support from Daiichi Sankyo outside the submitted work. Dr Couturaud reported receiving grants from Bristol Myers Squibb; personal fees from Bayer, AstraZeneca, and Bristol Myers Squibb; and travel support from Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Leo Pharma, InterMune, and Actelion outside the submitted work. Dr Huisman reported receiving grants from Pfizer-Bristol Myers Squibb Alliance, Bayer Health Care, ZonMw, the Dutch Heart Foundation outside the submitted work. Dr Yusen reported receiving personal fees from Ortho Pharmaceuticals for providing expert review of venous thromboembolism cases and relationship to hormonal contraceptive therapy, Organon for providing expert review of venous thromboembolism cases and relationship to hormonal contraceptive therapy, Merck for providing expert review of venous thromboembolism cases and relationship to hormonal contraceptive therapy, Portola for providing consulting related to the oral anticoagulant betrixaban, and Janssen for providing consulting related to the oral anticoagulant rivaroxaban and grants from Cyclomedica for funding as a co-investigator of a study of an imaging agent, Technegas, outside the submitted work. Dr Bikdeli reported being a consulting expert, on behalf of the plaintiff, for litigation related to 2 specific brand models of inferior vena cava filters. Dr Monreal reported receiving educational grants from Sanofi and Rovi Pharmaceuticals for research and personal fees from Sanofi and Leo Pharma for advisory committees outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Flow of Patients in a Study of the Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes

Figure 2.. Composite Outcome in a Study of the Effect of a Pulmonary Embolism Diagnostic Strategy on Clinical Outcomes

The median (IQR) observation time was 90 (70-90) days for the intervention group and 90 (76-90) days for the control group.