36-Month Clinical Outcomes of Patients with Venous Thromboembolism: GARFIELD-VTE

Abstract

Background: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide.

Methods: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries.

Findings: A total of 6582 (61.6%) patients had DVT alone, 4097 (38.4%) had PE ± DVT. At baseline, 98.1% of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6% at 3 months, 73.0% at 6 months, 54.2% at 12 months and 42.0% at 36 months. At 12-months follow-up, the incidences (95% confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n=565, 48.6%), followed by cardiac (n=94, 8.1%), and VTE (n=38, 3.2%). Most recurrent VTE events were DVT alone (n=564, 63.3%), with the remainder PE, (n=236, 27.3%), or PE in combination with DVT (n=63, 7.3%).

Interpretation: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population.

Trial Registration Details: (GARFIELD VTE, ClinicalTrials.gov identifier: NCT02155491)

Funding Information: This work was supported by the Thrombosis Research Institute (London, UK).

Declaration of Interests: Alexander G. G. Turpie: Honoraria from Bayer Pharma AG, Janssen. Sylvia Haas: Honoraria from Bayer Pharma AG, Bristol Myers Squibb, Daiichi-Sankyo, Pfizer, Portola, Sanofi. Walter Ageno: Honoraria from Boehringer Ingelheim, Bayer Pharma AG, Bristol Myers Squibb, Pfizer, Daiichi-Sankyo, Portola, Aspen, Sanofi. Research support from Bayer Pharma AG. Jeffrey I. Weitz: Research support from Canadian Institutes of Health Research, Heart and Stroke Foundation, and the Canadian Fund for Innovation. Honoraria from Alnylam, Anthos, Bayer Pharma AG, Boehringer-Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Merck, Novartis Pfizer, PhaseBio, and Servier. Samuel Z. Goldhaber: Research Support from Bayer Pharma AG, Boehringer-Ingelheim, BMS, BTG EKOS, Daiichi, Janssen, NHLBI, Thrombosis Research Institute. Consultancy fees from Bayer Pharma AG, Boehringer-Ingelheim. Shinya Goto: Research funding from Ono, Bristol Myers Squibb, Sanofi, and Pfizer. Personal fees from Thrombosis Research Institute and the American Heart Association. Renato D. Lopes: Research grants and personal fees from Bristol-Myers Squibb and Pfizer, personal fees from Boehringer Ingelheim and Bayer AG, research grants from Amgen Inc, GlaxoSmithKline, Medtronic PLC, and Sanofi Aventis. Chern-En Chiang: Honoraria from Astrazeneca, Boehringer Ingelheim, Daiichi-Sankyo, MSD, Novartis, Pfizer, and Sanofi. Harry Gibbs: Personal fees from Pfizer, Bayer, Boehringer Ingelheim. Peter Verhamme: Research support and honoraria from Bayer Healthcare, Boehringer, Daiichi-Sankyo, Anthos Pharmaceuticals, Portola, Leo-Pharma, BMS and Pfizer. Hugo ten Cate: research support from Bayer, consultant for Alveron. Shareholder Coagulation Profile. Second affiliation is Center of Thrombosis and Hemostasis (CTH), Gutenberg University Medical Center, Mainz, Germany. Juan Muntaner: Speaker fees from Bayer Pharma Latin America. Sebastian Schellong: Speaker fees from Bayer Pharma AG, Boehringer-Ingelheim, Bristol Meyer Squibb, Daiichi-Sankyo, Sanofi Aventis and Pfizer. Consultancy fees from Bayer Pharma AG, Boehringer-Ingelheim, Daiichi-Sankyo, Sanofi Aventis, Aspen and Pfizer. Paolo Prandoni: Personal fees from Bayer Pharma AG, Pfizer, Daiichi-Sankyo and Sanofi. Professor Ajay K Kakkar: Research grants from Bayer Pharma AG and Sanofi. Personal fees from Anthos Therapeutics, Bayer Pharma AG, Sanofi S.A, and Alfredo E. Farjat, Henri Bounameaux, Pantep Angchaisuksiri, Gloria Kayani, Eric Tse: None.

Ethics Approval Statement: The registry is conducted in accordance with the Declaration of Helsinki and guidelines from the International Conference on Harmonisation on Good Clinical Practice (GCP) and Good Pharmaco-epidemiological Practice (GPP) and adheres to all applicable national laws and regulations. Independent ethics committee for each participating country and the hospital based institutional review board approved the design of the registry. All patients provided written informed consent to participate. Confidentiality and anonymity of patients recruited into this registry were maintained.

Keywords: Venous thromboembolism, deep vein thrombosis, pulmonary embolism, registry, anticoagulation