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. 2023 Nov 15;5(6):758-772.
doi: 10.1016/j.jaccao.2023.09.003. eCollection 2023 Dec.

Cancer-Associated Thrombosis: Trends in Clinical Features, Treatment, and Outcomes From 2001 to 2020

Laurent Bertoletti  1   2   3 , Olga Madridano  4 , David Jiménez  5   6   7 , Alfonso Muriel  8 , Behnood Bikdeli  9   10   11   12 , Cihan Ay  13 , Javier Trujillo-Santos  14   15 , Marijan Bosevski  16 , Patricia Sigüenza  17 , Manuel Monreal  18
Affiliations

Cancer-Associated Thrombosis: Trends in Clinical Features, Treatment, and Outcomes From 2001 to 2020

Laurent Bertoletti et al. JACC CardioOncol. .

Abstract

Background: Despite advances in cancer and venous thromboembolism (VTE) management, the epidemiology of cancer-associated thrombosis management over time remains unclear.

Objectives: We analyzed data from the RIETE (Registro Informatizado de la Enfermedad Trombo Embólica) registry spanning 2001 to 2020 to investigate temporal trends in clinical characteristics and treatments for cancer-associated thrombosis.

Methods: Using multivariable survival regression, we examined temporal trends in risk-adjusted rates of symptomatic VTE recurrences, major bleeding, and death within 30 days after incident VTE.

Results: Among the 17,271 patients with cancer-associated thrombosis, there was a progressive increase in patients presenting with pulmonary embolism (from 44% in 2001-2005 to 55% in 2016-2020; P < 0.001 for trend), lung (from 12.7% to 18.1%; P < 0.001) or pancreatic cancer (from 3.8% to 5.6%; P = 0.003), and utilization of immunotherapy (from 0% to 7.4%; P < 0.001). Conversely, there was a decline in patients with prostate cancer (from 11.7% to 6.6%; P < 0.001) or carcinoma of unknown origin (from 3.5% to 0.7%; P < 0.001). At the 30-day follow-up, a reduction was observed in the proportion of patients experiencing symptomatic VTE recurrences (from 3.1% to 1.1%; P < 0.001), major bleeding (from 3.1% to 2.2%; P = 0.004), and death (from 11.9% to 8.4%; P < 0.001). Multivariable analyses revealed a decreased risk over time for VTE recurrence (adjusted subdistribution HR [asHR]: 0.94 per year; 95% CI: 0.92-0.98), major bleeding (asHR: 0.98; 95% CI: 0.96-0.99), and death (aHR: 0.97; 95% CI: 0.96-0.98).

Conclusions: In this multicenter study of cancer patients with VTE, there was a decline in thrombotic, hemorrhagic, and fatal events from 2001 to 2020. (Registro Informatizado de la Enfermedad Trombo Embólica [RIETE]; NCT02832245).

Keywords: anticoagulant; bleeding; cancer; survival; thrombosis.

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Conflict of interest statement

Dr Bertoletti has received personal fees and nonfinancial support from Aspen, Bayer, BMS-Pfizer, and Léo-Pharma and Johnson & Johnson; and has received grants, personal fees, and nonfinancial support from Merck Sharp & Dohme outside the submitted work. Dr Jimenez has received grants or contracts from Daiichi-Sankyo, Sanofi, and ROVI; and has received personal fees and honoraria for lectures from Bayer, Boehringer Ingelheim, BMS, Daiichi-Sankyo, Léo-Pharma, Pfizer, ROVI, and Sanofi outside the submitted work. Dr Bikdeli is supported by the Scott Schoen and Nancy Adams IGNITE Award from the Mary Horrigan Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital and a Career Development Award from the American Heart Association (#938814). Dr Ay has received honoraria for lectures from Bayer, BMS, Daiichi-Sankyo, Pfizer, and Sanofi outside the submitted work; and has served on Advisory Boards of Bayer, BMS, Daiichi-Sankyo, Pfizer, and Sanofi. Dr Trujillo-Santos has received personal fees and honoraria for lectures from Bayer, Boehringer Ingelheim, BMS, Daiichi-Sankyo, Léo-Pharma, Pfizer, ROVI, and Sanofi outside the submitted work. Dr Sigüenza has received support for attending meetings for Sanofi, ROVI, and Viatris. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Trends in the Use of Anticoagulant Drugs for Initial Venous Thromboembolism Therapy Low molecular weight heparins (LMWHs) remain the most commonly used anticoagulants for the initial treatment of cancer-associated thrombosis, with a recent increase in the use of direct oral anticoagulants (DOACs) since 2016. UFH = unfractionated heparin; VTE = venous thromboembolism.
Figure 2
Figure 2
Trends in Anticoagulant Drug Use Beyond the First Week of Venous Thromboembolism Therapy Beyond the first week of therapy, LMWHs have progressively replaced vitamin K antagonists (VKAs) for cancer-associated thrombosis maintenance therapy. Recently, there has been an increasing adoption of DOACs, especially since 2018. Abbreviations as in Figure 1.
Figure 3
Figure 3
Thirty-Day Unadjusted Crude Rates of Outcomes Over a 20-Year Period The unadjusted curves suggest a decline in death rates resulting from pulmonary embolism (PE) or hemorrhage over the last 20 years. The results are based on crude rates not considering competing risk.
Figure 4
Figure 4
Thirty-Day Unadjusted Crude Rates of Symptomatic VTE Recurrences and Major Bleeding Over a 20-Year Period The unadjusted curves suggest a decrease in the rates of symptomatic cancer-associated thrombosis recurrence and bleeding events over the last 20 years. The results are based on crude rates not considering competing risk. VTE = venous thromboembolism.
Figure 5
Figure 5
Trends in 30-Day Fatal Events Over a 20-Year Period The analysis of trends of 30-day HR (or subdistribution HR for competing risk analysis) (adjusted by moving average) shows a decrease in the HR of death by bleeding or pulmonary embolism (PE) and all-cause death. The risk of death caused by PE exhibits a significant decline beginning in 2007. Trends of 30-day HR (or subdistribution HR for competing risk analysis) adjusted using a moving average are depicted. We applied a smoothing technique by using a fifth-order moving average, with the SD serving as the descriptive measure for the values used in calculating these moving averages.
Figure 6
Figure 6
Trends in VTE Recurrences and Bleeding Over a 20-Year Period Trends in the 30-day HR (or sub-HR for competing risk analysis) for venous thromboembolism (VTE) recurrence and major bleeding are presented, with adjustments made using a moving average. The analysis was adjusted for potential confounding factors, showing a decrease in the HR (or sub-HR for competing risk analysis) for recurrent VTE and major bleeding over the last 20 years. However, no increase in bleeding events has been observed during recent years of analysis.
Central Illustration
Central Illustration
Advancements in Cancer-Associated Thrombosis Management Over a 20-Year Period This illustration portrays the trends in the 30-day adjusted HR (or subdistribution HR for competing risk analysis) of symptomatic venous thromboembolism (VTE) recurrences and major bleeding over a 20-year time period. The analysis was adjusted for potential confounding factors, showing a decrease in the HR (or subdistribution HR for competing risk analysis) for the recurrence of cancer-associated thrombosis and major bleeding, which has remained constant throughout the entire 20-year period. However, there has been no increase in bleeding events during the recent years of analysis. Trends are presented with adjustments made using a moving average. DVT = deep vein thrombosis; PE = pulmonary embolism; RIETE = Registro Informatizado de la Enfermedad Trombo Embólica.
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