Predictors of mortality from pulmonary embolism and their influence on clinical management -
Abstract Background New management, risk stratification and treatment strategies have become available over the last years for patients with acute pulmonary embolism (PE), potentially leading to changes in clinical practice and improvement of patients’ outcome. Methods The COntemporary management of Pulmonary Embolism (COPE) is a prospective, non-interventional, multicentre study in patients with acute PE evaluated at internal medicine, cardiology and emergency departments in Italy. The aim of the COPE study is to assess contemporary management strategies in patients with acute, symptomatic, objectively confirmed PE concerning diagnosis, risk stratification, hospitalization and treatment and to assess rates and predictors of in-hospital and 30-day mortality. The composite of death (either overall or PE-related) or clinical deterioration at 30 days from the diagnosis of PE, major bleeding occurring in hospital and up to 30 days from the diagnosis of PE and adherence to guidelines of the European Society of Cardiology (ESC) are secondary study outcomes. Participation in controlled trials on the management of acute PE is the only exclusion criteria. Expecting a 10–15%, 3% and 0.5% incidence of death for patients with high, intermediate or low-risk PE, respectively, it is estimated that 400 patients with high, 2100 patients with intermediate and 2500 with low-risk PE should be included in the study. This will allow to have about 100 deaths in study patients and will empower assessment of independent predictors of death. Conclusions COPE will provide contemporary data on in-hospital and 30-day mortality of patients with documented PE as well as information on guidelines adherence and its impact on clinical outcomes. Trail registration NCT number: NCT03631810.
This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation.The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (≤1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age ≥80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings.The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events.In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.
In a case-control study in patients with acute ischemic stroke and extracranial internal carotid artery (eICA) occlusion, thrombolytic treatment was associated with increased mortality. The aim of this cohort study was to assess the efficacy and safety of thrombolysis in patients with eICA occlusion compared to those without eICA occlusion.Consecutive patients treated with intravenous tissue-type plasminogen activator within 4.5 h from symptom onset included in the Safe Implementation of Thrombolysis in Stroke - International Stroke Thrombolysis Registry (SITS-ISTR) in 20 Italian centres were analyzed. Acute carotid occlusion was diagnosed using ultrasound examination, angio-CT scan or angio-MRI. Since the SITS-ISTR database did not plan to report the site of vessel occlusion, each participating center provided the code of the patient with eICA occlusion. Patients were divided into 2 groups, those with and those without eICA occlusion. Main outcome measures were: death, disability (modified Rankin Scale, mRS, 3-6) and any intracranial bleeding at 3 months. Multiple logistic regression analysis was performed to reveal predictors for main outcomes. The following variables of interest were included in the analysis: presence of eICA occlusion, age, gender, diabetes mellitus, hyperlipidemia, atrial fibrillation, congestive heart failure, previous stroke, current smoking, antiplatelet treatment at stroke onset, baseline NIHSS score, baseline blood glucose, cholesterol and blood pressure, history of hypertension and stroke onset to treatment time.A total of 1,761 patients without eICA occlusion and 137 with eICA occlusion were included in the study. At 3 months, 42 patients were lost to follow-up (3 with eICA occlusion). Death occurred in 30 (22.4%) patients with eICA occlusion and in 175 (10.2%) patients without (p < 0.0001). Death or disability at 3 months occurred in 91 of 134 patients with eICA occlusion (67.9%) compared with 654 of 1,722 patients without eICA occlusion (37.9%, p < 0.0001). No or minimal disability at 3 months (mRS 0-1) was reported in 25 (18.7%) patients with eICA occlusion and in 829 (48.2%) patients without (p < 0.0001). Any intracranial bleeding detected by CT or MRI at posttreatment imaging was seen in 16 (11.7%) patients with eICA occlusion and in 314 (17.8%) of those without (p = 0.09). The proportion of symptomatic intracerebral hemorrhage was 5.8% for patients with eICA occlusion and 8.0% for patients without (p = 0.16). At logistic regression analysis, eICA occlusion was associated with mortality (odds ratio, OR 5.7; 95% confidence interval, CI 2.9-11.1) and mortality or disability (OR 5.0; 95% CI 2.9-8.7) at 90 days.This cohort study in patients with acute ischemic stroke treated with thrombolysis showed an association between eICA occlusion and adverse outcome.
Background: The optimal duration of oral anticoagulant treatment after a first episode of pulmonary embolism remains uncertain. Objective: To evaluate the long-term clinical benefit of extending a 3-month course of oral anticoagulant therapy to 6 months (pulmonary embolism associated with temporary risk factors) or to 1 year (idiopathic pulmonary embolism) in patients with a first episode of pulmonary embolism. Design: Multicenter randomized study with independent, blinded assessment of the outcome events. Setting: 19 Italian hospitals. Patients: 326 patients who had had 3 months of oral anticoagulant therapy without experiencing recurrence or bleeding. Measurements: The primary study outcome was recurrence of symptomatic, objectively confirmed venous thromboembolism. Results: Among 165 patients assigned to extended anticoagulant therapy, 15 patients (9.1%) had a recurrence of venous thromboembolism (3.1% per patient-year; average follow-up, 34.9 months), as compared with 18 of 161 patients (11.2%) assigned to discontinue treatment (4.1% per patient-year; average follow-up, 32.7 months); the rate ratio was 0.81 (95% CI, 0.42 to 1.56). All but one of the recurrences occurred after anticoagulant treatment was discontinued. Nineteen recurrences (57.6%) were episodes of pulmonary embolism, two of which were fatal. Three major bleeding episodes were observed during extended anticoagulation (1.8%). Among patients with idiopathic venous thromboembolism, 11 of 90 patients assigned to extended anticoagulation and 11 of 91 patients assigned to discontinue treatment experienced a recurrence (relative risk, 0.99 [CI, 0.45 to 2.16]). Conclusion: Patients with pulmonary embolism have a substantial risk for recurrence after discontinuation of oral anticoagulation, regardless of treatment duration. Physicians should try to identify patients who are at high risk for recurrent venous thromboembolism and are therefore potential candidates for indefinite oral anticoagulant therapy. *For a list of the Warfarin Optimal Duration Italian Trial Investigators, see Appendix.
1554 Background: The association between venous thromboembolism (VTE) and cancer is well known. VTE represents the second cause of death in cancer patients. In some retrospective analysis, carried out using population and hospital-based registries, it has been reported that patients with cancer and VTE have a worse survival than those with cancer without VTE. Methods: MASTER ONCOLOGY is a prospective, multicenter, national, observational, case-control study specifically designed to identify VTE risk factors and to evaluate the influence of VTE on outcome of cancer patients with locally advanced or metastatic solid tumours. Patients in case (cancer patients with VTE) and control (cancer patients without VTE) groups have been matched for gender, age, cancer site, cancer histology and extension of disease. Information on patients, tumour characteristics, concomitant diseases, treatments, risk factors were registered. Survival data have been prospectively collected at 10 months and assessed through both Kaplan Meier method and Cox proportional hazards regression. Results: 611 patients were enrolled in the study by 51 Italian Centers. Of these, 237 cases and 339 controls were evaluable. The mean age was 64.7 (range 23-84) and 64.5 (range 41-87) years in cases and controls groups, respectively; the percentage of males was 43.0% and 41.9%. The most frequent tumour sites were colon, breast, lung, pancreas and stomach. Overall survival was statistically better for control patients as compared to case patients (p=0.0021). The raw HR was statistically significant: case patients had a risk of death 1.56 larger than controls (95% CI 1.23-1.98). Considering the complete model (using backward selection), the HR, due to patients status after adjustment for covariates, was 1.29 (95% CI 1.01-1.66). Conclusions: The study results demonstrate, for the first time, in a prospective and specifically designed study, that patients with cancer and VTE have a reduced survival compared to cancer patients without VTE.
