The risk of recurrent venous thromboembolism after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis: a systematic review and meta-analysis.

Background: The optimal duration of anticoagulation in patients with active cancer and venous thromboembolism (VTE) is unknown. Current clinical guidelines advocate anticoagulant therapy for 3-6 months and to continue anticoagulant therapy for as long as the cancer is active. However, an adequate systematic review on the rate of recurrent VTE after discontinuation of anticoagulant therapy has not been performed. Methods: For this systemic review and meta-analysis, we searched Embase.com, Medline (Ovid), Web of Science, Cochrane Library, and Google Scholar, from database inception to February 16, 2023, for studies on anticoagulant therapy in patients with cancer and the recurrence of venous thromboembolism after discontinuation of this therapy. We included randomised controlled trials and cohort studies published in English that reported on patients who met the following: cancer and a first VTE, completed at least 3 months of anticoagulant therapy, were followed after discontinuation of anticoagulant therapy, and with symptomatic recurrent VTE as an outcome during follow-up. Study-level data were requested from study authors. The primary outcome was the rate of recurrent VTE after discontinuation of anticoagulant therapy. A Bayesian random-effects meta-analysis was used to estimate the rate of recurrent VTE per 100 person-years for the pooled studies at different time intervals after discontinuation of anticoagulation therapy. We also calculated the cumulative VTE recurrence rate at different time intervals. Forest plots were mapped and the results were summarized by the median and 95% credible interval (CIs). This study was registered with PROSPERO, CRD42021249060. Findings: Of 3856 studies identified in our search, 33 studies were identified for inclusion. After requesting study-level data, 14 studies involving 1922 patients with cancer-associated thrombosis were included. The pooled rate of recurrent VTE per 100 person-years after discontinuation of anticoagulant therapy was 14.6 events (95% credible interval 6.5-22.8) in the first three months, decreasing to 1.1 events (95% CI 0.3-2.1) in year 2-3, and 2.2 events (95% CI 0.0-4.4) in year 3-5 after discontinuation of anticoagulant therapy. The cumulative VTE recurrence rate was 28.3% (95% CI 15.6-39.6%) at 1 year; 31.1% (95% CI 16.5-43.8%) at 2 years; 31.9% (95% CI 16.8-45.0%) at 3 years; and 35.0% (95% CI 16.8-47.4%) at 5 years after discontinuation of anticoagulant therapy. Interpretation: This meta-analysis demonstrates a high rate of recurrent VTE over time after discontinuation of anticoagulant therapy in patients with cancer-associated thrombosis. Our results support the current clinical guidelines to continue anticoagulant therapy in patients with active cancer. Funding: Erasmus MC.

Risks of Right Heart Catheterization and Right Ventricular Biopsy: A 12-year, Single-Center Experience.

OBJECTIVE: To study the incidence of complications when undergoing right heart catheterization (RHC) and right ventricular biopsy (RVB). METHODS: Complications following RHC and RVB are not well reported. We studied the incidence of death, myocardial infarction, stroke, unplanned bypass, pneumothorax, hemorrhage, hemoptysis, heart valve repair/replacement, pulmonary artery perforation, ventricular arrhythmias, pericardiocentesis, complete heart block, and deep vein thrombosis (primary endpoint) following these procedures. We also adjudicated the severity of tricuspid regurgitation and causes of in-hospital death following RHC. Diagnostic RHC procedures, RVB, multiple right heart procedures alone or combined with left heart catheterization, and complications from January 1, 2002, through December 31, 2013, were identified using the clinical scheduling system and electronic records at Mayo Clinic, Rochester, Minnesota. International Classification of Diseases, Ninth Revision billing codes were used. Registration was queried to identify all-cause mortality. All clinical events and echocardiograms for worsening tricuspid regurgitation were reviewed and adjudicated. RESULTS: A total of 17,696 procedures were identified. Procedures were categorized into those undergoing RHC (n=5556), RVB (n=3846), multiple right heart catheterization (n=776), and combined right and left heart catheterization procedures (n=7518). Primary endpoint was seen in 21.6 and 20.8 of 10,000 procedures for RHC and RVB, respectively. There were 190 (1.1%) deaths during hospital admission and none was related to the procedure. CONCLUSION: Complications following diagnostic RHC and RVB are seen in 21.6 and 20.8 procedures, respectively, of 10,000 procedures and all deaths were secondary to acute illness.

Prognostic Risk Stratification of Patients with Moderate Aortic Stenosis.

BACKGROUND: Currently risk stratification of moderate aortic stenosis (AS) is still incipient. The aim of this study was to identify prognostic factors in patients with moderate AS. METHODS: The prognosis of patients with moderate AS (1 < aortic valve area ≤ 1.5 cm2) stratified by left ventricular ejection fraction (LVEF; 50%), stroke volume index (SVI; 35 mL/m2), and elevated E/e' ratio (average, 14) was compared with that of the age- and sex-matched general population. RESULTS: Of 696 patients (median age, 77 years; aortic valve area 1.3 cm2; 57% men), 279 (40%) died during a median follow-up period of 3.4 years. Mortality was higher in patients with moderate AS than reference (mortality ratio, 2.43; 95% CI, 2.17-2.72). LVEF < 50%, SVI < 35 mL/m2, and elevated E/e' ratio were present in 113 (17%), 54 (8%), and 330 (54%) patients; mortality ratios were 3.89 (95% CI, 3.07-4.85), 6.40 (95% CI, 4.57-8.71), and 2.58 (95% CI, 2.21-3.00), respectively. Even if LVEF or SVI was preserved, the mortality ratio was more than twice than reference (P < .001), but elevated E/e' ratio could discriminate additional patients at higher risk (hazard ratio [HR], 2.71; 95% CI, 1.88-3.91). Two hundred one patients (29%) underwent aortic valve replacement at a median of 2.3 years after the diagnosis of moderate AS. LVEF < 50% (HR, 2.98; 95% CI, 1.39-6.56), SVI < 35 mL/m2 (HR, 3.34; 95% CI, 1.02-10.90) and elevated E/e' ratio (HR, 2.73; 95% CI, 1.26-5.94) were all associated with worse prognosis even if aortic valve replacement was performed. CONCLUSIONS: In patients with moderate AS, those with decreased LVEF and/or SVI are at high risk. Even if these parameters are preserved, patients with elevated E/e' ratios are at intermediate risk. Further investigation is warranted to assess whether earlier intervention could improve outcomes and reduced cardiac-related death among patients at high and intermediate risk.

Is Infection an Independent Risk Factor for Venous Thromboembolism? A Population-Based, Case-Control Study.

BACKGROUND: The independent association of recent infection with venous thromboembolism is uncertain. The study aims were to test both overall infection (site unspecified) and specific infection sites as potential risk factors for deep vein thrombosis and pulmonary embolism adjusting for other known venous thromboembolism factors. METHODS: By using Rochester Epidemiology Project resources, we identified all Olmsted County, Minnesota, residents with objectively diagnosed incident deep vein thrombosis or pulmonary embolism over the 13-year period 1988 to 2000 (cases; n = 1303) and 1 to 2 residents without venous thromboembolism matched to each case on age, sex, and incident venous thromboembolism date (controls; n = 1494). Using conditional logistic regression, we tested recent infection and infection site(s) for an association with venous thromboembolism, adjusting for body mass index, smoking, current/recent hospitalization with/without surgery, nursing home confinement, active cancer, trauma/fracture, leg paresis, prior superficial vein thrombosis, transvenous catheter/pacemaker, ischemic heart disease, congestive heart failure, chronic lung or renal disease, serious liver disease, asthma, diabetes mellitus, hormone therapy, and pregnancy/postpartum. RESULTS: A total of 513 cases (39.4%) and 189 controls (12.7%) had an infection in the previous 92 days (odds ratio, 4.5; 95% confidence interval, 3.6-5.5; P < .0001). In a multivariable analysis adjusting for common venous thromboembolism risk factors, pneumonia and symptomatic urinary tract, oral, intra-abdominal, and systemic bloodstream infections were associated with significantly increased odds of venous thromboembolism. CONCLUSIONS: Infection as a whole and specific infection sites in particular are independent risk factors for venous thromboembolism and should be considered as potential indications for venous thromboembolism prophylaxis.

Temporal Trends of Single-Photon Emission Computed Tomography Myocardial Perfusion Imaging in Patients With Coronary Artery Disease: A 22-Year Experience From a Tertiary Academic Medical Center.

BACKGROUND: There has been a gradual decline in the prevalence of abnormal stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging studies among patients without history of coronary artery disease (CAD). The trends of SPECT studies among patients with known CAD have not been evaluated previously. METHODS AND RESULTS: We assessed the Mayo Clinic nuclear cardiology database for all stress SPECT tests performed between January 1991 and December 2012 in patients with history of CAD defined as having previous myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting. The study cohort was divided into 5 time periods: 1991 to 1995, 1996 to 2000, 2001 to 2005, 2006 to 2010, and 2011 to 2012. There were 19 373 patients with a history of CAD who underwent SPECT between 1991 and 2012 (mean age, 66.2±10.9 years; 75.4% men). Annual utilization of SPECT in these patients increased from an average of 495 tests per year in 1991 to 1995 to 1425 in 2003 and then decreased to 552 tests in 2012 without evidence for substitution with other stress modalities. Asymptomatic patients initially increased until 2006 and then decreased. Patients with typical angina decreased, whereas patients with dyspnea and atypical angina increased. High-risk SPECT tests significantly decreased, and the percentage of low-risk SPECT tests increased despite decreased SPECT utilization between 2003 and 2012. Almost 80% of all tests performed in 2012 had a low-risk summed stress score compared with 29% in 1991 (P<0.001). CONCLUSIONS: In Mayo Clinic, Rochester, annual SPECT utilization in patients with previous CAD increased between 1992 and 2003, but then decreased after 2003. High-risk SPECT tests declined, whereas low-risk tests increased markedly. Our results suggest that among patients with a history of CAD, SPECT was being increasingly utilized in patients with milder CAD. This trend parallels reduced utilization of other stress modalities, coronary angiography, reduced smoking, and greater utilization of optimal medical therapy for prevention and treatment of CAD.

Reasons for the persistent incidence of venous thromboembolism.

Reasons for trends in venous thromboembolism (VTE) incidence are uncertain. It was our objective to determine VTE incidence trends and risk factor prevalence, and estimate population-attributable risk (PAR) trends for each risk factor. In a population-based cohort study of all residents of Olmsted County, Minnesota from 1981-2010, annual incidence rates were calculated using incident VTE cases as the numerator and age- and sex-specific Olmsted County population estimates as the denominator. Poisson regression models were used to assess the relationship of crude incidence rates to year of diagnosis, age at diagnosis, and sex. Trends in annual prevalence of major VTE risk factors were estimated using linear regression. Poisson regression with time-dependent risk factors (person-years approach) was used to model the entire population of Olmsted County and derive the PAR. The age- and sex-adjusted annual VTE incidence, 1981-2010, did not change significantly. Over the time period, 1988-2010, the prevalence of obesity, surgery, active cancer and leg paresis increased. Patient age, hospitalisation, surgery, cancer, trauma, leg paresis and nursing home confinement jointly accounted for 79 % of incident VTE; obesity accounted for 33 % of incident idiopathic VTE. The increasing prevalence of obesity, cancer and surgery accounted in part for the persistent VTE incidence. The PAR of active cancer and surgery, 1981-2010, significantly increased. In conclusion, almost 80 % of incident VTE events are attributable to known major VTE risk factors and one-third of incident idiopathic VTE events are attributable to obesity. Increasing surgery PAR suggests that concurrent efforts to prevent VTE may have been insufficient.

Is lipid lowering therapy an independent risk factor for venous thromboembolism? A population-based case-control study.

INTRODUCTION: The independent effect of lipid lowering therapy (LLT) on venous thromboembolism (VTE) risk is uncertain. OBJECTIVE: To test statin and non-statin LLT as potential VTE risk factors. METHODS: Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively diagnosed incident VTE (cases) over the 13-year period, 1988-2000 (n=1340), and one to two matched controls (n=1538). We reviewed their complete medical records for baseline characteristics previously identified as independent VTE risk factors, and for statin and non-statin LLT. Using conditional logistic regression, we tested the overall effect of LLT on VTE risk and also separately explored the role of statin versus that of non-statin LLT, adjusting for other baseline characteristics. RESULTS: Among cases and controls, 74 and 111 received statin LLT, and 32 and 50 received non-statin LLT, respectively. Univariately, and after individually controlling for other potential VTE risk factors (i.e., BMI, trauma/fracture, leg paresis, hospitalization for surgery or medical illness, nursing home residence, active cancer, central venous catheter, varicose veins, prior superficial vein thrombosis, diabetes, congestive heart failure, angina/myocardial infarction, stroke, peripheral vascular disease, smoking, anticoagulation), LLT was associated with decreased odds of VTE (unadjusted OR=0.73; p=0.03). When considered separately, statin and non-statin LLT were each associated with moderate, non-significant lower odds of VTE. After adjusting for angina/myocardial infarction, each was significantly associated with decreased odds of VTE (OR=0.63, p<0.01 and OR=0.61, p=0.04, respectively). CONCLUSIONS: LLT is associated with decreased VTE risk after adjusting for known risk factors.

Population-based study of the use of cardiac stress imaging and referral for coronary angiography and repeated revascularization after coronary artery bypass graft surgery.

OBJECTIVE: To assess stress single-photon emission computed tomography (SPECT) and stress echocardiography use after coronary artery bypass grafting (CABG) and their effect on referral for coronary angiography and revascularization. PATIENTS AND METHODS: The referral, timing, and results of stress imaging after CABG; referral for coronary angiography and revascularization; and all-cause mortality were assessed in this longitudinal, population-based, retrospective study of 1138 Olmsted County, Minnesota, patients undergoing CABG between January 1, 1993, and December 31, 2003. RESULTS: A total of 570 patients (50.1%) underwent a stress imaging study (341 SPECT and 229 echocardiography) during the study period. Of the 1138 patients, 372 (32.7%) were referred for coronary angiography, and 144 of those patients (12.7%) underwent repeated revascularization (132 percutaneous revascularization and 12 CABG). The median interval between CABG and the index stress imaging study was 3.0 years (25th-75th percentile, 1.2-5.7 years). The results of 75.7% (258 of 341) of the stress SPECT studies and 70.7% (162 of 229) of the stress echocardiograms were abnormal. Seventy-six of 570 patients (13.3%) referred for stress imaging underwent coronary angiography within 180 days after the stress test. Repeated coronary revascularization was performed in 25 patients (4.4%) who underwent a stress imaging study within the preceding 180 days. The 5- and 10-year survival rates in the entire study cohort (83.5% and 65.1%, respectively) were not significantly different than predicted for the age- and sex-matched Minnesota population. CONCLUSION: Half of this community-based population of patients with CABG underwent stress SPECT or echocardiography during median follow-up of 8.9 years. Despite that approximately 75% of the results of stress imaging studies were abnormal, subsequent referral for coronary angiography within 180 days was low (13.3%), and the yield for repeated revascularization was very low (4.4%).

The association of active cancer with venous thromboembolism location: a population-based study.

OBJECTIVE: To test active cancer for an association with venous thromboembolism (VTE) location. PATIENTS AND METHODS: Using the resources of the Rochester Epidemiology Project, we identified all Olmsted County, MN, residents with incident VTE during the 35-year period 1966-2000 (N = 3385). We restricted analyses to residents with objectively diagnosed VTE during the 17-year period from January 1, 1984, to December 31, 2000 (N = 1599). For each patient, we reviewed the complete medical records in the community for patient age, gender, and most recent body mass index at VTE onset; VTE event type and location; and previously identified independent VTE risk factors (ie, surgery, hospitalization for acute medical illness, active cancer, leg paresis, superficial venous thrombosis, and varicose veins). Using logistic regression we tested active cancer for an association with each of 4 symptomatic VTE locations (arm or intra-abdominal deep venous thrombosis [DVT], intra-abdominal DVT, pulmonary embolism, and bilateral leg DVT), adjusted for age, gender, body mass index, and other VTE risk factors. RESULTS: In multivariate analyses, active cancer was independently associated with arm or intra-abdominal DVT (odds ratio [OR], 1.76; P = .01), intra-abdominal DVT (OR, 2.22; P = .004), and bilateral leg DVT (OR, 2.09; P = .02), but not pulmonary embolism (OR, 0.93). CONCLUSION: Active cancer is associated with VTE location. Location of VTE may be useful in decision making regarding cancer screening.