Increasing Incidence and Declining Mortality After Cancer-Associated Venous Thromboembolism: A Nationwide Cohort Study

Ording, Anne Gulbech; Skjøth, Flemming; Søgaard, Mette; Højen, Anette Arbjerg; Overvad, Thure Filskov; Noble, Simon; Goldhaber, Samuel Z.; Larsen, Torben Bjerregaard

doi:10.1016/j.amjmed.2021.01.031

Cited by 20 publications

(14 citation statements)

References 39 publications

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“…Cancer incidence is rising and venous thromboembolism remains a common and potentially fatal complication among patients with cancer. 1,2 Cancer-associated venous thromboembolism poses a burden on healthcare systems, disrupts cancer treatment, and contributes to emotional distress and physical discomfort. 3,4 Patients with venous thromboembolism also carry a substantial risk of recurrence.…”

Section: Introductionmentioning

confidence: 99%

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy

et al. 2022

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The Khorana score is recommended for guiding primary venous thromboembolism prophylaxis in cancer patients, but its clinical utility overall and across cancer types remains debatable. Also, some previous validation studies have ignored competing risk of death, hereby potentially overestimating venous thromboembolism risk. We identified ambulatory cancer patients initiating chemotherapy without other indications for anticoagulation using Danish health registries and estimated six-month cumulative incidence of venous thromboembolism stratified by Khorana levels. Analyses were conducted with and without considering death as competing risk using the Kaplan-Meier method versus the cumulative incidence function. Analyses were performed overall and stratified by cancer types. Of 40,218 patients, 35.4% were categorized by Khorana as low risk (score 0), 53.6% as intermediate risk (score 1-2) and 10.9% as high risk (score ≥3). Considering competing risk of death, the corresponding six-month risks of venous thromboembolism were 1.5% (95% CI 1.3-1-7), 2.8% (95% CI 2.6-3.1), and 4.1% (95% CI 3.5-4.7), respectively. Among patients recommended anticoagulation by guidelines (Khorana score ≥2), six-month risk was 3.6% (95% CI 3.3-3.9). Kaplan-Meier analysis overestimated incidence up to 23% compared with competing risk analyses. Using the guideline-recommended threshold of ≥2, the Khorana score did not risk stratify patients with hepatobiliary or pancreatic cancer, lung cancer, and gynecologic cancer. In conclusion, the Khorana score was able to stratify ambulatory cancer patients according to risk of venous thromboembolism, but not for all cancer types. Absolute risks varied by methodology but were lower than in key randomized trials. Thus, although certain limitations with outcome identification using administrative registries apply, the absolute benefit of implementing routine primary thromboprophylaxis in an unselected cancer population may be smaller than seen in randomized trials.

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Section: Introductionmentioning

confidence: 99%

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy

et al. 2022

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“…Patients with cancer pose a particular challenge with respect to venous thromboembolism, as reflected by the multiple thrombosis guidelines that are dedicated to this specific population [ 61 , 62 ]. The incidence of both venous thrombosis, bleeding, and recurrent venous thrombosis is high, thereby complicating the decisions on treatment and secondary prophylaxis [ 63 , 64 , 65 ]. Adding to this, the treatment decisions are often taken by the treating oncologist or hematologist without their consultancy with a thrombosis specialist [ 66 ].…”

Section: Recommendations For Specific Populationsmentioning

confidence: 99%

Long-Term Management of Pulmonary Embolism: A Review of Consequences, Treatment, and Rehabilitation

Højen

Nielsen

Overvad

et al. 2022

JCM

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The concept of pulmonary embolism is evolving. Recent and emerging evidence on the treatment of specific patient populations, its secondary prevention, long-term complications, and the unmet need for rehabilitation has the potential to change clinical practice for the benefit of the patients. This review discusses the recent evidence from clinical trials, observational studies, and guidelines focusing on anticoagulation treatment, rehabilitation, emotional stress, quality of life, and the associated outcomes for patients with pulmonary embolism. Guidelines suggest that the type and duration of treatment with anticoagulation should be based on prevalent risk factors. Recent studies demonstrate that an anticoagulant treatment that is longer than two years may be effective and safe for some patients. The evidence for extended treatment in cancer patients is limited. Careful consideration is particularly necessary for pulmonary embolisms in pregnancy, cancer, and at the end of life. The rehabilitation and prevention of unnecessary deconditioning, emotional distress, and a reduced quality of life is an important, but currently they are unmet priorities for many patients with a pulmonary embolism. Future research could demonstrate optimal anticoagulant therapy durations, follow-ups, and rehabilitation, and effective patient-centered decision making at the end of life. A patient preferences and shared decision making should be incorporated in their routine care when weighing the benefits and risks with primary treatment and secondary prevention.

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“…Venous thromboembolism remains a frequent and potentially serious complication among patients with cancer 1‐4 . In recent years, guidelines have recommended primary thromboprophylaxis with anticoagulation in selected cancer patients initiating systemic treatment following risk stratification with the Khorana score, a simple, point‐based risk score originally developed to assess risk of venous thromboembolism in patients initiating chemotherapy 5,6 .…”

Section: Introductionmentioning

confidence: 99%

“…Venous thromboembolism remains a frequent and potentially serious complication among patients with cancer. 1 , 2 , 3 , 4 In recent years, guidelines have recommended primary thromboprophylaxis with anticoagulation in selected cancer patients initiating systemic treatment following risk stratification with the Khorana score, a simple, point‐based risk score originally developed to assess risk of venous thromboembolism in patients initiating chemotherapy. 5 , 6 The benefit of primary anticoagulant thromboprophylaxis guided by the Khorana score has even been explored in randomized trials, but not specifically for patients treated with immune checkpoint inhibitors, and the Khorana score was developed in an era prior to clinical use of these agents.…”

Section: Introductionmentioning

confidence: 99%

The Khorana score and venous and arterial thrombosis in patients with cancer treated with immune checkpoint inhibitors: A Danish cohort study

Overvad

Skjøth

Piazza

et al. 2022

Journal of Thrombosis and Haemostasis

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Background:Thrombosis is common among patients with cancer. Primary thromboprophylaxis guided by the Khorana score is endorsed by guidelines but recommendations rely mainly on data from patients treated with chemotherapy.Objectives: To explore if the Khorana score could risk stratify patients with cancer treated with immune checkpoint inhibitors according to risk of venous and arterial thrombosis.Patients/Methods: The study population and Khorana score were defined using administrative Danish health registries. The primary outcome was 6-month risk of venous thromboembolism after initiation of checkpoint inhibitor treatment. Secondary outcomes were arterial thrombosis and any thromboembolic event. Death was considered a competing risk event.Results: Among 3946 patients with cancer initiating checkpoint inhibitor treatment without other indications for anticoagulation, the overall 6-month incidence of venous thromboembolism was 2.6% (95% confidence interval [CI]: 2.1-3.1). Risks were 2.1% (95% CI: 1.5-3.0), 2.6% (95% CI: 2.0-3.4), and 3.7% (95% CI: 2.1-5.9) in low (score 0), intermediate (score 1-2), and high risk (score ≥3) Khorana categories, respectively. Among patients eligible for primary thromboprophylaxis according to guidelines (Khorana score ≥2), risk of venous thromboembolism was 4.1% (95% CI: 3.1-5.4). Higher Khorana risk category was also associated with higher 6-month risk of both arterial thrombosis and any thromboembolic events. Conclusions:The Khorana score was able to risk stratify patients with cancer treated with immune checkpoint inhibitors according to 6-month risk of thromboembolic events. Risks of venous thromboembolism were lower than in randomized thromboprophylaxis trials, thus questioning the absolute benefit of routine primary thromboprophylaxis in an unselected population of patients treated with immune checkpoint inhibitors.

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Increasing Incidence and Declining Mortality After Cancer-Associated Venous Thromboembolism: A Nationwide Cohort Study

Cited by 20 publications

References 39 publications

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy

Validation of the Khorana score for predicting venous thromboembolism in 40 218 patients with cancer initiating chemotherapy

Long-Term Management of Pulmonary Embolism: A Review of Consequences, Treatment, and Rehabilitation

The Khorana score and venous and arterial thrombosis in patients with cancer treated with immune checkpoint inhibitors: A Danish cohort study

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