TY - JOUR
T1 - Redefining clinical venous thromboembolism phenotypes
T2 - a novel approach using latent class analysis
AU - de Winter, Maria A.
AU - Uijl, Alicia
AU - Büller, Harry R.
AU - Carrier, Marc
AU - Cohen, Alexander T.
AU - Hansen, John-Bjarne
AU - Kaasjager, Karin H. A. H.
AU - Kakkar, Ajay K.
AU - Middeldorp, Saskia
AU - Raskob, Gary E.
AU - Sørensen, Henrik Toft
AU - Wells, Philip S.
AU - Nijkeuter, Mathilde
AU - Dorresteijn, Jannick A. N.
N1 - Funding Information: M.C. reports research funding from BMS, Leo Pharma , and Pfizer and honorarium from Bayer , Sanofi, BMS, Leo Pharma, Servier, and Pfizer (all fees are paid to the institution). A.T.C. reports consulting fees, membership on the advisory boards, and research support from Abbott , AbbVie , ACI Clinical, Alexion Pharmaceuticals , Aplagon Ltd, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, BTG, Cambridge Healthcare Research, Daiichi Sankyo, EmstoPA Ltd, EPG Health, Guidepoint Global, Gulf Coast Developments, Janssen, Johnson & Johnson, Leo Pharma, LifeSciences Consulting, Medscape, McKinsey, Navigant, North Star Communications, ONO Pharmaceuticals, Pfizer, Portola Pharmaceuticals, Sanofi, Takeda, Total CME, and Windrose Consulting Group. A.K.K. reports research support from Bayer and Sanofi and personal fees from Bayer, Sanofi, and Anthos Inc. S.M. reports grants and personal fees from Daiichi Sankyo, Bayer, Pfizer, and Boehringer Ingelheim and personal fees from Portola/Alexion, AbbVie, BMS, Pfizer, and Norgine (all fees are paid to her institution). G.E.R. reports consultancy fees or honoraria from Bayer HealthCare Pharmaceuticals Inc, Bristol-Myers Squibb, Daiichi Sankyo Inc, Eli Lilly and Company, Itreas, Janssen Global Services LLC, Medscape, Novartis, Pfizer, Portola Pharmaceuticals, Teherex, and XaTrek; honoraria from ACC Oklahoma, Canadian Cardiovascular Society, Japanese Circulation Society, M3 LTD, MD Magazine and North American Thrombosis Forum; and stock or stock option ownership for AbbVie, Inc, ACADIA Pharmaceuticals Inc, Altimmune Inc, Arch Therapeutics, Atea Pharmaceuticals, Biomarin, Cohbar, Eli Lilly and Company, EsperionTherapeutics, Gilead Sciences Inc, GlaxoSmithKline LLC, Incyte Corporation, Merck, Moderna, NKTR, Pfizer, Precigen, Sangamo Therapeutics Inc, Vaxart, and ZioPharm Oncology. P.S.W. reports grants and speaker fees from BMS/Pfizer and speaker fees from Bayer Healthcare (all fees are paid to his institution). The other authors have no competing interests to disclose. Publisher Copyright: © 2022 International Society on Thrombosis and Haemostasis
PY - 2023/3/1
Y1 - 2023/3/1
N2 - Background: Patients with venous thromboembolism (VTE) are commonly classified by the presence or absence of provoking factors at the time of VTE to guide treatment decisions. This approach may not capture the heterogeneity of the disease and its prognosis. Objectives: To evaluate clinically important novel phenotypic clusters among patients with VTE without cancer and to explore their association with anticoagulant treatment and clinical outcomes. Methods: Latent class analysis was performed with 18 baseline clinical variables in 3062 adult patients with VTE without active cancer participating in PREFER in VTE, a noninterventional disease registry. The derived latent classes were externally validated in a post hoc analysis of Hokusai-VTE (n = 6593), a randomized trial comparing edoxaban with warfarin. The associations between cluster membership and anticoagulant treatment, recurrent VTE, bleeding, and mortality after initial treatment were studied. Results: The following 5 clusters were identified: young men cluster (n = 1126, 37%), young women cluster (n = 215, 7%), older people cluster (n = 1106, 36%), comorbidity cluster (n = 447, 15%), and history of venous thromboembolism cluster (n = 168, 5%). Patient characteristics varied by age, sex, medical history, and treatment patterns. Consistent clusters were evident on external validation. In Cox proportional hazard models, recurrence risk was lower in the young women cluster (hazard ratio [HR], 0.27; 95% CI, 0.12-0.61) compared with the comorbidity cluster, after adjusting for extended anticoagulation. The risk of bleeding was lower in young men, young women, and older people clusters (HR, 0.50; 95% CI, 0.38-0.66; HR, 0.23; 95% CI, 0.11-0.46; and HR, 0.55; 95% CI 0.41-0.73, respectively). Conclusion: The heterogeneity of VTE cases extends beyond the distinction between provoked and unprovoked VTE.
AB - Background: Patients with venous thromboembolism (VTE) are commonly classified by the presence or absence of provoking factors at the time of VTE to guide treatment decisions. This approach may not capture the heterogeneity of the disease and its prognosis. Objectives: To evaluate clinically important novel phenotypic clusters among patients with VTE without cancer and to explore their association with anticoagulant treatment and clinical outcomes. Methods: Latent class analysis was performed with 18 baseline clinical variables in 3062 adult patients with VTE without active cancer participating in PREFER in VTE, a noninterventional disease registry. The derived latent classes were externally validated in a post hoc analysis of Hokusai-VTE (n = 6593), a randomized trial comparing edoxaban with warfarin. The associations between cluster membership and anticoagulant treatment, recurrent VTE, bleeding, and mortality after initial treatment were studied. Results: The following 5 clusters were identified: young men cluster (n = 1126, 37%), young women cluster (n = 215, 7%), older people cluster (n = 1106, 36%), comorbidity cluster (n = 447, 15%), and history of venous thromboembolism cluster (n = 168, 5%). Patient characteristics varied by age, sex, medical history, and treatment patterns. Consistent clusters were evident on external validation. In Cox proportional hazard models, recurrence risk was lower in the young women cluster (hazard ratio [HR], 0.27; 95% CI, 0.12-0.61) compared with the comorbidity cluster, after adjusting for extended anticoagulation. The risk of bleeding was lower in young men, young women, and older people clusters (HR, 0.50; 95% CI, 0.38-0.66; HR, 0.23; 95% CI, 0.11-0.46; and HR, 0.55; 95% CI 0.41-0.73, respectively). Conclusion: The heterogeneity of VTE cases extends beyond the distinction between provoked and unprovoked VTE.
KW - anticoagulants
KW - bleeding
KW - cluster analysis
KW - deep venous thrombosis
KW - venous thromboembolism
UR - http://www.scopus.com/inward/record.url?scp=85149178357&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jtha.2022.11.013
DO - https://doi.org/10.1016/j.jtha.2022.11.013
M3 - Article
C2 - 36696208
SN - 1538-7933
VL - 21
SP - 573
EP - 585
JO - Journal of thrombosis and haemostasis
JF - Journal of thrombosis and haemostasis
IS - 3
ER -