TY - JOUR
T1 - Long-term risk of recurrent venous thromboembolism among patients receiving extended oral anticoagulant therapy for first unprovoked venous thromboembolism
T2 - A systematic review and meta-analysis
AU - Khan, Faizan
AU - Tritschler, Tobias
AU - Kimpton, Miriam
AU - Wells, Philip S
AU - Kearon, Clive
AU - Weitz, Jeffrey I
AU - Büller, Harry R
AU - Raskob, Gary E
AU - Ageno, Walter
AU - Couturaud, Francis
AU - Prandoni, Paolo
AU - Palareti, Gualtiero
AU - Legnani, Cristina
AU - Kyrle, Paul A
AU - Eichinger, Sabine
AU - Eischer, Lisbeth
AU - Becattini, Cecilia
AU - Agnelli, Giancarlo
AU - Vedovati, Maria Cristina
AU - Geersing, Geert-Jan
AU - Takada, Toshihiko
AU - Cosmi, Benilde
AU - Aujesky, Drahomir
AU - Marconi, Letizia
AU - Palla, Antonio
AU - Siragusa, Sergio
AU - Bradbury, Charlotte A
AU - Parpia, Sameer
AU - Mallick, Ranjeeta
AU - Lensing, Anthonie W A
AU - Gebel, Martin
AU - Grosso, Michael A
AU - Shi, Minggao
AU - Thavorn, Kednapa
AU - Hutton, Brian
AU - Le Gal, Gregoire
AU - Rodger, Marc
AU - Fergusson, Dean
N1 - Funding Information:
FK, T Tritschler, MK, PW, CK, JW, SP, KT, GLG, MR, and DF are members of the CanVECTOR Network; the Network receives grant funding from the Canadian Institutes of Health Research (Funding Reference: CDT‐142654). FK holds the Frederick Banting and Charles Best doctoral research scholarship from the Canadian Institutes of Health Research. JW holds the Canada Research Chair (Tier I) in Thrombosis and the Heart and Stroke Foundation of Canada J. F. Mustard Chair in Cardiovascular Research. T Tritschler holds an Early Postdoc. Mobility Award from the Swiss National Science Foundation (SNSF P2ZHP3_177999) and a Fellowship Award from the CanVECTOR Network. GLG holds the Chair on Diagnosis of Venous Thromboembolism at the Department of Medicine, University of Ottawa, and a Clinician‐Scientist Award from the Heart and Stroke Foundation of Canada. MR is the McGill University Harry Webster Thorp Professor of Medicine.
Funding Information:
FK, T Tritschler, MK, PW, CK, JW, SP, KT, GLG, MR, and DF are members of the CanVECTOR Network; the Network receives grant funding from the Canadian Institutes of Health Research (Funding Reference: CDT-142654). FK holds the Frederick Banting and Charles Best doctoral research scholarship from the Canadian Institutes of Health Research. JW holds the Canada Research Chair (Tier I) in Thrombosis and the Heart and Stroke Foundation of Canada J. F. Mustard Chair in Cardiovascular Research. T Tritschler holds an Early Postdoc. Mobility Award from the Swiss National Science Foundation (SNSF P2ZHP3_177999) and a Fellowship Award from the CanVECTOR Network. GLG holds the Chair on Diagnosis of Venous Thromboembolism at the Department of Medicine, University of Ottawa, and a Clinician-Scientist Award from the Heart and Stroke Foundation of Canada. MR is the McGill University Harry Webster Thorp Professor of Medicine.
Funding Information:
PW reports receiving honoraria for advisory board meetings from Bayer Healthcare, Sanofi, and Daiichi Sankyo, and Research Funding from BMS/Pfizer. JW reports serving as a consultant for which he has received honoraria from Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, Daiichi Sankyo, Ionis, Janssen, Merck, Novartis, Pfizer, Anthos, PhaseBio, Itreas, and Servier, outside the submitted work. GR reports receiving consultancy fees or honoraria from Anthos, Bristol‐Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Janssen, Novartis, Pfizer, Portola, and Tetherex; and personal fees from Bayer Healthcare, Bristol‐Myers Squibb, Boehringer Ingelheim, Eli Lilly, Daiichi Sankyo, Janssen, Pfizer, Portola, Itreas, Tetherex, Anthos, and Novartis, outside the submitted work. WA reports grants from Bayer, and personal fees from Bayer, Daiichi Sankyo, Boehringer Ingelheim, BMS Pfizer, Aspen, Sanofi, Portola, and Janssen, outside the submitted work. FC reports receiving research grant support from Pfizer, fees for board memberships or symposia from Bayer, Bristol‐Myers Squibb/Pfizer and Astra Zeneca, and travel support from Bayer, Bristol‐Myers Squibb/Pfizer, Daiichi Sankyo, Boehringer Ingelheim, Leo Pharma, Intermune and Actelion, outside the submitted work. GP reports serving on advisory boards for Alfasigma, Pfizer, BMS and Roche, outside the submitted work. CB reports receiving personal fees from Bayer HealthCare, Bristol Myers Squibb, and Daiichi Sankyo, outside the submitted work. GA reports receiving personal fees from Bristol Myers Squibb, Bayer HealthCare, and Daiichi Sankyo, outside the submitted work. BC reports receiving personal fees from Daiichi Sankyo, Werfen, and Sanofi, outside the submitted work. SS reports grants from Bayer, SOBI, NOVARTIS, and personal fees from Bayer, Sobi, Novartis, Amgen, and Janssen, outside the submitted work. TL and MG report being an employee of Bayer. M. Grosso and MS report being employees of Daiichi Sankyo. BH reports receiving honoraria from Cornerstone Research Group for provision of methodologic advice related to systematic reviews and meta‐analysis. GLG reports other support from Portola Pharmaceuticals, Boehringer Ingelheim, Pfizer, BristolMyers Squibb, LEO Pharma, Daiichi Sankyo, Bayer, Sanofi, and bioMerieux, outside the submitted work. The remaining authors declare no competing financial interests.
Publisher Copyright:
© 2021 International Society on Thrombosis and Haemostasis.
PY - 2021/11
Y1 - 2021/11
N2 - BACKGROUND: The long-term risk for recurrent venous thromboembolism (VTE) during extended anticoagulation for a first unprovoked VTE is uncertain.OBJECTIVES: To determine the incidence of recurrent VTE during extended anticoagulation of up to 5 years in patients with a first unprovoked VTE.METHODS: MEDLINE, EMBASE, and the Cochrane CENTRAL were searched to identify randomized trials and prospective cohort studies reporting recurrent VTE among patients with a first unprovoked VTE who were to receive anticoagulation for a minimum of six additional months after completing ≥3 months of initial treatment. Unpublished data on number of recurrent VTE and person-years, obtained from authors of included studies, were used to calculate study-level incidence rate, and random-effects meta-analysis was used to pool results.RESULTS: Twenty-six studies and 15 603 patients were included in the analysis. During 11 631 person-years of follow-up, the incidence of recurrent VTE and fatal pulmonary embolism per 100 person-years was 1.41 (95% CI, 1.03-1.84) and 0.09 (0.04-0.16), with 5-year cumulative incidences of 7.1% (3.0%-13.2%) and 1.2% (0.4%-4.6%), respectively. The incidence of recurrent VTE was 1.08 (95% CI, 0.77-1.44) with direct oral anticoagulants and 1.55 (1.01-2.20) with vitamin K antagonists. The case-fatality rate of recurrent VTE was 4.9% (95% CI, 2.2%-8.7%).CONCLUSIONS: In patients with a first unprovoked VTE, the long-term risk of recurrent VTE during extended anticoagulation is low but not negligible. Thus, clinicians and patients should be aware of this risk and take appropriate and timely action in case of suspicion of recurrent VTE. Estimates from this study can be used to advise patients on what to expect while receiving extended anticoagulation, and estimate the net clinical benefit of extended treatment to guide long-term management of unprovoked VTE.
AB - BACKGROUND: The long-term risk for recurrent venous thromboembolism (VTE) during extended anticoagulation for a first unprovoked VTE is uncertain.OBJECTIVES: To determine the incidence of recurrent VTE during extended anticoagulation of up to 5 years in patients with a first unprovoked VTE.METHODS: MEDLINE, EMBASE, and the Cochrane CENTRAL were searched to identify randomized trials and prospective cohort studies reporting recurrent VTE among patients with a first unprovoked VTE who were to receive anticoagulation for a minimum of six additional months after completing ≥3 months of initial treatment. Unpublished data on number of recurrent VTE and person-years, obtained from authors of included studies, were used to calculate study-level incidence rate, and random-effects meta-analysis was used to pool results.RESULTS: Twenty-six studies and 15 603 patients were included in the analysis. During 11 631 person-years of follow-up, the incidence of recurrent VTE and fatal pulmonary embolism per 100 person-years was 1.41 (95% CI, 1.03-1.84) and 0.09 (0.04-0.16), with 5-year cumulative incidences of 7.1% (3.0%-13.2%) and 1.2% (0.4%-4.6%), respectively. The incidence of recurrent VTE was 1.08 (95% CI, 0.77-1.44) with direct oral anticoagulants and 1.55 (1.01-2.20) with vitamin K antagonists. The case-fatality rate of recurrent VTE was 4.9% (95% CI, 2.2%-8.7%).CONCLUSIONS: In patients with a first unprovoked VTE, the long-term risk of recurrent VTE during extended anticoagulation is low but not negligible. Thus, clinicians and patients should be aware of this risk and take appropriate and timely action in case of suspicion of recurrent VTE. Estimates from this study can be used to advise patients on what to expect while receiving extended anticoagulation, and estimate the net clinical benefit of extended treatment to guide long-term management of unprovoked VTE.
KW - anticoagulant therapy
KW - prognosis
KW - pulmonary embolism
KW - systematic review
KW - venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=85113201816&partnerID=8YFLogxK
U2 - 10.1111/jth.15491
DO - 10.1111/jth.15491
M3 - Review article
C2 - 34379859
SN - 1538-7933
VL - 19
SP - 2801
EP - 2813
JO - Journal of thrombosis and haemostasis : JTH
JF - Journal of thrombosis and haemostasis : JTH
IS - 11
ER -