Impact of breast-, gastrointestinal-, and lung cancer on prognosis in patients with first-time pulmonary embolism: A Danish nationwide cohort study.

BACKGROUND: Pulmonary embolism (PE) is described as a prognostic factor in patients with cancer however, the prognostic impact of PE remains unknown. This study investigated, the 1-year prognosis following PE in patients with breast-, gastrointestinal-, or lung cancer stratified by cancer status. METHODS: All Danish patients with first-time PE from 2008 to 2018 were included. Cancer status was categorized as no cancer, history of cancer, non-active cancer and active cancer. Unadjusted and age-stratified 1-year risk of death was estimated using the Kaplan-Meier estimator. Cause of death was reported using the Aalen-Johansen method. RESULTS: Of 35,679 patients with PE, 18% had a breast-, gastrointestinal-, or lung cancer. Patients with cancer were older compared with no cancer (69.8 years [IQR: 56.2-79.8]). One-year risk of death (95% confidence interval) for active breast-, gastrointestinal-, and lung cancer was 49.5% (44.0%-54.9%), 75.0% (72.5%-77.4%) and 80.1% (78.0%-82.3%) respectively, compared with 18.9% (18.4%-19.3%) for no cancer. Age-stratified analysis revealed no association with increasing age in non-active lung cancer and all active cancers. Further, non-cardiovascular death accounted for an increasing proportion by cancer status (no cancer < history of cancer < non-active cancer < active cancer). CONCLUSIONS: One-year risk of death was dependent on both cancer type and status; no association with age was found for patients with active cancers. Non-cardiovascular death was leading in non-active and active cancers. Thus, the occurrence of first-time PE could be regarded as a marker of cancer severity for patients with breast-, gastrointestinal-, and lung cancer.

Infrequent transition to direct oral anticoagulants in patients with cancer.

INTRODUCTION: Pharmacokinetic drug-drug interactions (DDIs) are challenging aspects of direct oral anticoagulant (DOAC) therapy in patients with cancer. We evaluated the prevalence of potential DOAC/antineoplastic agent DDIs and the one-year cumulative incidence of switching from low-molecular-weight heparin (LMWH) to a DOAC in patients with cancer. METHODS: Patients with cancer and an indication of LMWH were included from Herlev and Gentofte Hospital, Denmark, in the 2014-2019 period. Follow-up was initiated when the first dose of LMWH was dispensed. Data were obtained from electronic medical records. One-year cumulative incidence of switching from LMWH to DOAC was estimated using the Aalen-Johansen estimator. Potential DDIs were evaluated using a report from the European Heart Rhythm Association (EHRA) and a review by Hellfritzsch et al. RESULTS. A total of 161 patients were included with a median age of 70.8 (interquartile range: 64.2-76.1) years. The one-year cumulative incidence of switching from LMWH to DOAC was 32% (95% confidence intervals: 21-43%) in patients eligible for DOACs. Using the EHRA report, a total of 24% of antineoplastic agents were not identified. This percentage decreased to 8% using data from Hellfritzsch et al. CONCLUSIONS. In patients with cancer, the one-year cumulative incidence of switching from LMWH to DOAC was less-t 35% in patients eligible for DOAC, revealing a potential for improved anticoagulant treatment. Furthermore, contemporary data elaborated on potential DDIs between DOACs/antineoplastic agents. FUNDING: "Helsefonden" (21-B-0350) and the "Karen Elise Jensens Fonden" (29-4-2021) funded the study. TRIAL REGISTRATION: Not relevant.

Cannabis for chronic pain: cardiovascular safety in a nationwide Danish study.

BACKGROUND AND AIMS: A rising number of countries allow physicians to treat chronic pain with medical cannabis. However, recreational cannabis use has been linked with cardiovascular side effects, necessitating investigations concerning the safety of prescribed medical cannabis. METHODS: Using nationwide Danish registers, patients with chronic pain initiating first-time treatment with medical cannabis during 2018-21 were identified and matched 1:5 to corresponding control patients on age, sex, chronic pain diagnosis, and concomitant use of other pain medication. The absolute risks of first-time arrhythmia (atrial fibrillation/flutter, conduction disorders, paroxysmal tachycardias, and ventricular arrhythmias) and acute coronary syndrome were reported comparing medical cannabis use with no use. RESULTS: Among 1.88 million patients with chronic pain (46% musculoskeletal, 11% cancer, 13% neurological, and 30% unspecified pain), 5391 patients claimed a prescription of medical cannabis [63.2% women, median age: 59 (inter-quartile range 48-70) years] and were compared with 26 941 control patients of equal sex- and age composition. Arrhythmia was observed in 42 and 107 individuals, respectively, within 180 days. Medical cannabis use was associated with an elevated risk of new-onset arrhythmia {180-day absolute risk: 0.8% [95% confidence interval (CI) 0.6%-1.1%]} compared with no use [180-day absolute risk: 0.4% (95% CI 0.3%-0.5%)]: a risk ratio of 2.07 (95% CI 1.34-2.80) and a 1-year risk ratio of 1.36 (95% CI 1.00-1.73). No significant association was found for acute coronary syndrome [180-day risk ratio: 1.20 (95% CI 0.35-2.04)]. CONCLUSIONS: In patients with chronic pain, the use of prescribed medical cannabis was associated with an elevated risk of new-onset arrhythmia compared with no use-most pronounced in the 180 days following the initiation of treatment.

Short- and Long-Term Mortality for Patients With and Without a Cancer Diagnosis Following Pulmonary Embolism in Denmark, 2000 to 2020: A Nationwide Study.

BACKGROUND: New treatment regimens have been introduced in the past 20 years, which may influence the short- and long-term prognosis for patients with and without a cancer diagnosis following pulmonary embolism. However, newer studies investigating these trends are lacking. Therefore, we aimed to investigate the 30- and 31- to 365-day mortality following pulmonary embolism. METHODS AND RESULTS: Using the Danish nationwide registries, patients with a diagnosis of pulmonary embolism between 2000 and 2020 were included. Age- and sex-standardized 30- and 31- to 365-day mortality was calculated and stratified by cancer status. In total, 60 614 patients (29.6% with recent cancer; mean age, 68.2 years) were included. The 30-day mortality for patients with no recent cancer decreased from 19.1% (95% CI, 17.9%-20.4%) in 2000 to 7.3% (95% CI, 6.7%-8.0%) in 2018 to 2020 (hazard ratio [HR], 0.36 [95% CI, 0.32-0.40]; P<0.001). The 30-day mortality for patients with recent cancer decreased from 32.2% (95% CI, 28.8%-36.6%) to 14.1% (95% CI, 12.7%-15.5%) (HR, 0.38 [95% CI, 0.33-0.44]; P<0.001). The 31- to 365-day mortality for patients with no recent cancer decreased from 12.5% (95% CI, 11.4%-13.6%) to 9.4% (95% CI, 8.6%-10.2%) (HR, 0.73 [95% CI, 0.64-0.83]; P<0.001).The 31- to 365-day mortality for patients with recent cancer remained stable: 39.4% (95% CI, 35.1%-43.7%) to 38.3% (95% CI, 35.9%-40.6%) (HR, 0.97 [95% CI, 0.84-1.12]; P=0.69). CONCLUSIONS: From 2000 to 2020, improvements were observed in 30-day mortality following pulmonary embolism regardless of cancer status. For patients with recent cancer, 31- to 365-day mortality did not improve, whereas a minor improvement was observed for patients without recent cancer.

Patient mortality following new-onset heart failure stratified by cancer type and status.

AIM: Expected 1-year survival is essential to risk stratification of patients with heart failure (HF); however, little is known about the 1-year prognosis of patients with HF and cancer. Thus, the objective was to investigate the 1-year prognosis following new-onset HF stratified by cancer status in patients with breast, gastrointestinal, or lung cancer. METHODS AND RESULTS: All Danish patients with new-onset HF from 2000 to 2018 were included. Cancer status was categorized as history of cancer (no cancer-related contact within 5 years of HF diagnosis), non-active cancer (curative intended procedure administered) and active cancer. Standardized 1-year all-cause mortality was reported using G-computation. Age-stratified 1-year all-cause mortality was estimated using the Kaplan-Meier estimator. In total, 193 359 patients with HF were included, 7.3% had either a breast, gastrointestinal, or lung cancer diagnosis. Patients with cancer were older and more comorbid than patients without cancer. Standardized 1-year all-cause mortality (95% confidence intervals) was 24.6% (23.0-26.2%), 27.1% (25.5-28.6%), and 29.9% (25.9-34.0%) for history of breast, gastrointestinal and lung cancer, respectively, which was comparable to patients with non-active cancers. For active breast, gastrointestinal and lung cancer, standardized 1-year all-cause mortality was 36.2% (33.8-38.6%), 49.0% (47.2-50.9%), and 61.6% (59.7-63.5%), respectively. One-year all-cause mortality increased incrementally with age, except for active lung cancer. CONCLUSION: Standardized 1-year all-cause mortality was comparable for patients with history of cancer and non-active cancer regardless of cancer type, but varied comprehensively for active cancers. Prognostic impact of age was limited for active lung cancer. Thus, granular stratification of cancer is necessary for optimized management of new-onset HF.

Temporal Trends in Noncardiovascular Morbidity and Mortality Following Acute Myocardial Infarction.

BACKGROUND: Due to improved management, diagnosis, and care of myocardial infarction (MI), patients may now survive long enough to increasingly develop serious noncardiovascular conditions. OBJECTIVES: This study aimed to test this hypothesis by investigating the temporal trends in noncardiovascular morbidity and mortality following MI. METHODS: We conducted a registry-based nationwide cohort study of all Danish patients with MI during 2000 to 2017. Outcomes were cardiovascular and noncardiovascular mortality, incident cancer, incident renal disease, and severe infectious disease. RESULTS: From 2000 to 2017, 136,293 consecutive patients were identified (63.2% men, median age 69 years). The 1-year risk of cardiovascular mortality between 2000 to 2002 and 2015 to 2017 decreased from 18.4% to 7.6%, whereas noncardiovascular mortality decreased from 5.8% to 5.0%. This corresponded to an increase in the proportion of total 1-year mortality attributed to noncardiovascular causes from 24.1% to 39.5%. Furthermore, increases in 1-year risk of incident cancer (1.9%-2.4%), incident renal disease (1.0%-1.6%), and infectious disease (5.5%-9.1%) were observed (all P trend <0.01). In analyses standardized for changes in patient characteristics, the increased risk of cancer in 2015 to 2017 compared with 2000 to 2002 was no longer significant (standardized risk ratios for cancer: 0.99 [95% CI: 0.91-1.07]; renal disease: 1.28 [95% CI: 1.15-1.41]; infectious disease: 1.28 [95% CI: 1.23-1.34]). CONCLUSIONS: Although cardiovascular mortality following MI improved substantially during 2000 to 2017, the risk of noncardiovascular morbidity increased. Moreover, noncardiovascular causes constitute an increasing proportion of post-MI mortality. These findings suggest that further attention on noncardiovascular outcomes is warranted in guidelines and clinical practice and should be considered in the design of future clinical trials.

The Validity of a New Procedure-Based Definition of Cancer Status in Patients with Breast-, Lung- and Colorectal Cancer in the Danish National Patient Registry.

Background/Aim: The Danish National Patient Registry (DNPR) provides unique epidemiological insight, but often lacks granular data. We propose a procedure-based definition of cancer status in patients with breast-, lung- and colorectal cancer, which can be applied to administrative health databases. New definitions of cancer status are needed as mortality and morbidity are closely linked to cancer status, yet most studies only use duration since cancer diagnosis as a severity marker. The aim of the study was to validate a new pragmatic definition. Methods: Medical journals of 600 patients, with breast-, lung- and colorectal cancer from the Department of Oncology at Herlev-Gentofte Hospital were retrospectively reviewed. We defined active cancer as a cancer diagnosis, not followed by a potentially curative procedure within 6 months of the diagnosis. The remaining patients were characterized as having non-active cancer. This dichotomization was then compared to a cancer status assessment based on treatment received and paraclinical test such as their first post-procedural control scan. Based on this comparison, we calculated the positive predictive value (PPV) of our definitions of active and non-active cancer. Results: The calculated PPVs for active breast-, lung- and colorectal cancer were 87% (CI 95%: 0.74-0.99), 91% (CI 95%: 0.87-0.96) and 82% (CI 95%: 0.73-0.91). The PPVs for non-active breast-, lung- and colorectal cancer were 95% (CI 95%: 0.92-0.99), 91% (CI 95%: 0.82-0.99) and 73% (CI 95%: 0.66-0.81), respectively. Conclusion: We found an overall high PPV for both active and non-active cancer across all three types of cancer.

Risk and timing of venous thromboembolism in patients with gastrointestinal cancer: a nationwide Danish cohort study.

AIMS: Cancer is a well-known risk factor of venous thromboembolism (VTE). Some cancers are believed to be more thrombogenic. The purpose of this study was to investigate the characteristics of patients with incident gastrointestinal cancers (GI) and their associated 1-year risk and timing of venous thromboembolic events and the 1-year mortality. METHODS: This study was a retrospective cohort study. Through Danish nationwide registries, all patients with first-time GI cancer diagnosis from 2008 to 2018 were identified. Incident VTE events were identified within a 1-year follow-up after GI cancer diagnosis using the Aalen-Johansen estimator. Cox proportional-hazard models were applied to investigate risk factors for VTE events and the impact of VTE on mortality. RESULTS: A total of 87 069 patients were included and stratified by cancer types: liver (5.8%), pancreatic (12.0%), gastric (6.9%), small intestinal (1.9%), colorectal (61.8%), oesophageal (7.3%) and gallbladder (3%). Most VTE events happened close to onset of the cancer diagnosis with declining events by time. The 1-year cumulative incidence of VTE differed according to cancer type with pancreatic cancer being most thrombogenic (7.8%), and colorectal and liver cancer being the least (3.6%). Prior VTE, heart failure, chronic obstructive pulmonary disease (COPD), liver disease, chronic kidney disease (CKD) and diabetes increased the VTE risk. Overall, the patients with GI cancer had high 1-year mortality of 33.3% with patients with pancreatic cancer having the highest mortality (70.3%). CONCLUSION: We found that most VTE events happen close to onset of the GI cancer diagnosis and thrombogenicity differed by type of GI cancer, ranging from 7.8% in patients with pancreatic cancer to 3.6% in colorectal and patients with liver cancer. Prior VTE, heart failure, COPD, liver disease, CKD and DM were associated with increased risk of VTE.

Prognosis of acute coronary syndrome stratified by cancer type and status - a nationwide cohort study.

BACKGROUND: To investigated the prognosis of the most prevalent cancers (breast-, gastrointestinal-, and lung cancer), according to cancer status (i.e., active-, non-active-, history of-, and no cancer), following first-time of acute coronary syndrome (ACS). METHODS: Danish nationwide registers were used to identify patients with first-time ACS from 2000-2018. Patients were stratified according to cancer type and status. Hazard ratios (HR) estimated by adjusted Cox regression models for 1year all-cause mortality reported. Further absolute risks of 1year cardiovascular versus non-cardiovascular death and 30-day cumulative incidence of coronary angiograms (CAG) was estimated, using the Aalen-Johansen non-parametric method, with competing risk of death. RESULTS: We identified 150,478 (95.7%) with no cancer, 2,370 (1.5%) with history of cancer, 2,712 (1.7%) with non-active cancer and 1,704 (1.1%) with active cancer. Cancer patients were older with more comorbidities than patients with no cancer. When compared with no cancer, we found HRs (95% confidence intervals) of 1.71 (1.44-2.02), 2.47 (2.23-2.73) and 4.22 (3.87-4.60) correspondingly for active breast-, gastrointestinal-, and lung cancer. Increased HRs were also found for non-active cancers, but not for history of cancer. Cardiovascular disease was the leading cause of death in all patients. Among patients with active breast-, gastrointestinal-, and lung cancer 43%, 43%, and 31% underwent CAG, correspondingly, compared with 77% of patients without cancer. CONCLUSIONS: Active- and non-active cancers were associated with an increased 1-year all-cause mortality compared with patients with history of cancer and no cancer. Cardiovascular disease was the leading cause of death; notably CAG was less frequently performed in cancer patients.

"No one told me anything about it and I cannot explain it": Illness perception in symptomatic and asymptomatic patients with cancer-associated thrombosis.

INTRODUCTION: Patients with cancer, have reported cancer-associated thrombosis (CAT), a distressing event in their overall illness. However, whether the clinical presentation of CAT; symptomatic versus asymptomatic, impacts illness perception is poorly elucidated. The aim of this study was to explore illness perception in patients with CAT, stratified by the clinical presentation. MATERIALS AND METHODS: In a qualitative design, we conducted a three-step workshop. Patients were included from a specialised cardiology care unit for oncology patients. Data analysis was performed using framework analysis. The analytic framework was based on the five components of illness perception: (1) identity of illness, (2) causal beliefs, (3) timeline beliefs, (4) beliefs about control/cure and (5) consequences. RESULTS: Elleven patients with CAT participated in the workshop; five symptomatic and six asymptomatic. Whitin each category of illness perception following notions emerged (1) the identity of CAT was only tangible for symptomatic participants, (2) the aetiology was considered important information for symptomatic participants, which was in contrast to asymptomatic participants, (3) asymptomatic participant did not consider recurrent CAT a threat towards their health, (4) asymptomatic participants were prone to information overload, whilst information was imperative to the sense of control in symptomatic participants, (5) low molecular weight heparin treatment was accepted in symptomatic participants due to remission of symptoms. CONCLUSIONS: The clinical presentation of CAT (asymptomatic/symptomatic) proved essential to illness perception. These findings indicate that information level and communication within the medical consultation, should actively consider the clinical presentation of CAT in order to optimize management and compliance.