Original Investigation
Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism

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Abstract

Background

The long-term effect of thrombolytic treatment of pulmonary embolism (PE) is unknown.

Objectives

This study investigated the long-term prognosis of patients with intermediate-risk PE and the effect of thrombolytic treatment on the persistence of symptoms or the development of late complications.

Methods

The PEITHO (Pulmonary Embolism Thrombolysis) trial was a randomized (1:1) comparison of thrombolysis with tenecteplase versus placebo in normotensive patients with acute PE, right ventricular (RV) dysfunction on imaging, and a positive cardiac troponin test result. Both treatment arms received standard anticoagulation. Long-term follow-up was included in the third protocol amendment; 28 sites randomizing 709 of the 1,006 patients participated.

Results

Long-term (median 37.8 months) survival was assessed in 353 of 359 (98.3%) patients in the thrombolysis arm and in 343 of 350 (98.0%) in the placebo arm. Overall mortality rates were 20.3% and 18.0%, respectively (p = 0.43). Between day 30 and long-term follow-up, 65 deaths occurred in the thrombolysis arm and 53 occurred in the placebo arm. At follow-up examination of survivors, persistent dyspnea (mostly mild) or functional limitation was reported by 36.0% versus 30.1% of the patients (p = 0.23). Echocardiography (performed in 144 and 146 patients randomized to thrombolysis and placebo, respectively) did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension (CTEPH) was confirmed in 4 (2.1%) versus 6 (3.2%) cases (p = 0.79).

Conclusions

Approximately 33% of patients report some degree of persistent functional limitation after intermediate-risk PE, but CTEPH is infrequent. Thrombolytic treatment did not affect long-term mortality rates, and it did not appear to reduce residual dyspnea or RV dysfunction in these patients. (Pulmonary Embolism Thrombolysis study [PEITHO]; NCT00639743)

Key Words

chronic thromboembolic pulmonary hypertension
long-term survival
prognosis
pulmonary embolism
thrombolysis

Abbreviations and Acronyms

CTEPH
chronic thromboembolic pulmonary hypertension
PE
pulmonary embolism
RV
right ventricular

Cited by (0)

This work was supported by grants from the Federal Ministry of Education and Research (BMBF; 01KG0802, 01EO1003, and 01EO1503) of Germany; grants from the Programme Hospitalier de Recherche Clinique (PHRC; AOM 03063, AOM 08231, and AOM 10171) of France; and by a grant from the market authorization holder of tenecteplase, Boehringer Ingelheim, to the trial sponsor, Assistance Publique Hôpitaux de Paris. Dr. Konstantinides has received consultant fees and lecture honoraria from Bayer HealthCare, Boehringer Ingelheim, Daiichi-Sankyo, Pfizer, and Bristol-Myers Squibb (BMS); has received payment for travel accommodation and meeting expenses from Bayer HealthCare; and has received institutional grants from Boehringer Ingelheim, Bayer HealthCare, and Daiichi-Sankyo. Dr. Vicaut has received honoria for advisory board membership and lectures from AstraZeneca, Bayer HealthCare, Bristol-Myers Squibb, Daiichi-Sankyo, Eli Lilly, Johnson & Johnson, Merck Sharpe & Dohme, and Pfizer; has received consulting fees from Pfizer, Bristol-Myers Squibb, Eli Lilly, Celgene, Novartis, and Abbott; and has received institutional grants from Boehringer Ingelheim. Dr. Danays is an employee of Boehringer Ingelheim. Dr. Becattini has received lecture honoraria from Bayer HealthCare, Pfizer, Bristol-Myers Squibb, and Boehringer Ingelheim. Dr. Bouvaist has received payment for travel accommodation and meeting expenses and lecture honoraria from Bayer HealthCare, AstraZeneca, Medtronic, GlaxoSmithKline, and Actelion; and has received institutional grants from Biosensor. Dr. Couturaud has received research grant support from Pfizer; has been a co-investigator in clinical trials with Bayer, Bristol-Myers Squibb, Boehringher Ingelheim, AstraZeneca, GlaxoSmithKline, Leo Pharma, Pfizer, Roche, Novartis, Merck Sharpe & Dohme, Daiichi-Sankyo, Gilead; has received fees for scientific board memberships or symposia from Bristol-Myers Squibb, Boehringer Ingelheim, Bayer HealthCare, Merck Sharpe & Dohme, and AstraZeneca; and has received travel support from Bristol-Myers Squibb, AstraZeneca, Bayer HealthCare, Daiichi-Sankyo, Leo Pharma, Roche, and Actelion. Dr. Kupatt has received lecture honoraria from Boehringer Ingelheim. Dr. Lang has received consultant fees and lecture honoraria from AOP Orphan Pharmaceuticals, Actelion, Bayer-Schering, AstraZeneca, Servier, Cordis, Medtronic, GlaxoSmithKline, Novartis, Pfizer, and United Therapeutics; and was an investigator in trials involving products of these companies. Dr. Lankeit has received consultant fees and lecture honoraria from Bayer HealthCare, Daiichi-Sankyo, Pfizer, Bristol-Myers Squibb, and Actelion. Dr. Meneveau has received payment for travel accommodation or meeting expenses from Bayer HealthCare, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Daiichi-Sankyo; is a member of the scientific advisory board for Bayer HealthCare, Pfizer, Bristol-Myers Squibb, and Daiichi-Sankyo; has received consultant fees and lecture honoraria paid to his institution from Bayer HealthCare, Pfizer, Bristol-Myers Squibb, AstraZeneca, St. Jude Medical, and Daiichi-Sankyo; and has received institutional grants from Boehringer Ingelheim, Bayer HealthCare, and Daiichi-Sankyo. Dr. Meyer has received reimbursement for travel accommodation or meeting expenses from Bayer HealthCare and Daiichi-Sankyo; is a member of the scientific advisory board of Leo Pharma; has received consultant fees and lecture honoraria paid to his institution from Bayer HealthCare, Pfizer, Bristol-Myers Squibb, and Daiichi-Sankyo; and has received institutional grants from Boehringer Ingelheim. Dr. Pruszczyk has received payment for travel accommodation or meeting expenses, consultant fees, and lecture honoraria from Bayer HealthCare, Pfizer, and Boehringer Ingelheim. Dr. Sanchez has received payment for travel accommodation or meeting expenses from Bayer HealthCare, GlaxoSmithKline, Actelion, Boehringer Ingelheim, and Chiesi; is a member of the scientific advisory board for Actelion, Bayer HealthCare, Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, and Chiesi; has received consultant fees and lecture honoraria paid to his institution from Actelion, Bayer HealthCare, Pfizer, Bristol-Myers Squibb, GlaxoSmithKline, and Chiesi; and has received institutional grants from Bayer HealthCare, Actelion, Daiichi-Sankyo, and Portola. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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