Coexisting cancer in patients with atrial fibrillation (AF) has been associated with thromboembolism and bleeding. We used Danish population‐based medical databases to conduct a population‐based cohort study that included all AF patients who redeemed a prescription for vitamin K antagonists (VKA) or non‐VKA oral anticoagulant (NOAC) between July 2004 and December 2013. We characterized these patients according to the presence (N = 11,855) or absence (N = 56,264) of a cancer diagnosis before redemption of their oral anticoagulant prescription, and then examined their 1‐year risk of thromboembolic or bleeding complications or death. We next used Cox regression to compare the hazard ratios for complications among VKA‐ or NOAC‐treated AF patients with versus without a cancer diagnosis, after adjusting for sex, age, and CHA₂DS₂ VASc score. One‐year risks of thromboembolic complications in AF patients who redeemed a VKA prescription were similar in those with (6.5%) and without (5.8%) cancer [hazard ratio (HR) 1.0 (95% confidence interval (CI): 0.93, 1.1)]. This also was found for bleeding complications (5.4% vs. 4.3%, HR 1.1 [95% CI: 1.0, 1.2]). For AF patients with cancer who redeemed a NOAC prescription, risks were also similar for thromboembolic complications (4.9% of cancer patients vs. 5.1% of noncancer patients, HR 0.80 [95% CI: 0.61, 1.1]), and for bleeding complications (4.4% vs. 3.1%, HR 1.2 [95% CI: 0.92, 1.7]). The absolute risks of thromboembolic or bleeding complications were nearly the same in patients with and without cancer who redeemed prescription for VKAs or NOACs.

The incidence of cancer-associated venous thromboembolism has increased, but whether short-term mortality after cancer-associated venous thromboembolism has changed remains uncertain. We investigated whether the increasing incidence of venous thromboembolism in cancer patients is associated with a change in mortality. We used administrative medical registries to identify a cohort of all Danish patients diagnosed with a first primary cancer from 2006 to 2017. We examined temporal changes in 1-year risks of venous thromboembolism and in mortality risks at 30 days and 1 year after venous thromboembolism. Cox regression was used to assess changes in mortality rate ratios over time. We included 350,272 cancer patients (median age 68 years, 49.1% female), of whom 8167 developed venous thromboembolism within 1 year after cancer diagnosis. The cumulative 1-year risk of venous thromboembolism was 1.8% in 2006-2008, increasing to 2.8% for patients diagnosed in 2015-2017. The 30-day mortality after venous thromboembolism decreased from 15.1% in 2006-2008 to 12.7% in 2015-2017, and the 1-year mortality decreased from 52.4% to 45.8%, equivalent to a hazard ratio (HR) of 0.83 (95% confidence interval [CI], 0.75-0.90). This pattern of declining 1-year mortality was consistent for patients with pulmonary embolism, HR 0.79 (95% CI, 0.69-0.90), and deep venous thrombosis, HR 0.76 (95% CI, 0.67-0.87). Lower mortality over time was evident across all strata of cancer stage, cancer type, and cancer treatment. The 1-year risk of venous thromboembolism after a first primary cancer diagnosis in Denmark increased during 2006-2017. This increase was accompanied by declining mortality.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication of cancer. It is unknown whether comorbidity interacts clinically with prostate cancer (PC) to increase the VTE rate beyond that explained by PC and comorbidity alone, for example, by delaying diagnosis or precluding treatment.METHODS: A nationwide, registry‐based cohort study of all 44,035 Danish patients diagnosed with PC from 1995 to 2011 and 213,810 men from the general population matched 5:1 on age, calendar time, and comorbidities. The authors calculated VTE rate ratios and the interaction contrast as a measure on the additive scale of the excess VTE rate explained by synergy between PC and comorbidity.RESULTS: In total, 849 patients in the PC cohort and 2360 men from the general population had VTE during 5 years of follow‐up, and their risk of VTE was 2.2% and 1.3%, respectively. The 1‐year VTE standardized rate among PC patients who had high comorbidity levels was 15 per 1000 person‐years (PYs) (95% confidence interval, 6.8‐24 per 1000 PYs), and 29% of that rate was explained by an interaction between PC and comorbidity. The VTE risk was increased among older patients, those with metastases, those with high Gleason scores, those in the D'Amico high‐risk group, and those who underwent surgery.CONCLUSIONS: PC interacted clinically with high comorbidity levels and increased the VTE rate. Because of the large PC burden, reducing VTEs associated with comorbidities may have an impact on VTE risk and the potential to improve prognosis. Clinical interactions between high levels of comorbidity and PC on the risk of VTE were observed. Almost 30% of all episodes of VTE occurred among patients who had high levels of comorbidity. Cancer 2015;121:3692–3699. © 2015 American Cancer Society.

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. 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. 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. 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. 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.

Venous thromboembolism (VTE) is a common complication in patients starting cancer therapies for non-small-cell lung cancer (NSCLC). We examined the risk and timing of VTE in patients with stage IIIA, IIIB to C, and stage IV NSCLC according to received cancer treatments. A nationwide registry-based cohort study of patients recorded in the Danish Lung Cancer Registry (2010-2021) followed for 1 year after entry into the registry to assess the incidence of VTE. The Aalen-Johansen estimator was used to calculate the risk of VTE after treatment commencement with chemotherapy, radiotherapy, chemoradiation, immunotherapy, and targeted therapy. Among the 3475 patients with stage IIIA, 4047 with stage IIIB to C, and 18,082 patients with stage IV cancer, the 1-year risk of VTE was highest in the first 6 months and varied markedly by cancer stage and cancer treatment. In stage IIIA, VTE risk was highest with chemotherapy (3.9%) and chemoradiation (4.1%). In stage IIIB to C, risks increased with chemotherapy (5.2%), immunotherapy (9.4%), and targeted therapy (6.0%). Stage IV NSCLC showed high risk with targeted therapy (12.5%) and immunotherapy (12.2%). The risk was consistently higher for pulmonary embolism than deep vein thrombosis. VTE risks vary substantially according to cancer treatments and cancer stages. The highest risk was observed in the initial 6 months of therapy initiation. These insights emphasize the need for tailored risk assessment and vigilance in managing VTE complications in patients with NSCLC. Further research is needed to optimize individual thromboprophylaxis strategies for patients with unresectable and metastatic NSCLC.