The European Society of Cardiology (ESC) has proposed an updated risk stratification model for death in patients with acute pulmonary embolism based on clinical scores (Pulmonary Embolism Severity Index (PESI) or simplified PESI (sPESI)), right ventricle dysfunction (RVD) and elevated serum troponin (2014 ESC model).We assessed the ability of the 2014 ESC model to predict 30-day death after acute pulmonary embolism. Consecutive patients with symptomatic, confirmed pulmonary embolism included in prospective cohorts were merged in a collaborative database. Patients' risk was classified as high (shock or hypotension), intermediate-high (RVD and elevated troponin), intermediate-low (RVD or increased troponin or none) and low (sPESI 0). Study outcomes were death and pulmonary embolism-related death at 30 days.Among 906 patients (mean±sd age 68±16, 489 females), death and pulmonary embolism-related death occurred in 7.2% and 4.1%, respectively. Death rate was 22% in "high-risk" (95% CI 14.0-29.8), 7.7% in "intermediate-high-risk" (95% CI 4.5-10.9) and 6.0% in "intermediate-low-risk" patients (95% CI 3.4-8.6). One of the 196 "low-risk" patients died (0.5%, 95% CI 0-1.0; negative predictive value 99.5%).By using the 2014 ESC model, RVD or troponin tests would be avoided in about 20% of patients (sPESI 0), preserving a high negative predictive value. Risk stratification in patients at intermediate risk requires further improvement.
Summary The outcomes of thromboprophylactic trials have been debated for decades. Recently, the 9th edition of the American College of Chest Physicians (ACCP) evidence-based clinical practice guidelines based their strong recommendations only on patient-important outcomes. Practically, symptoms were considered the crucial element. Consequently, studies that primarily aimed at reducing venographic thrombi were considered less pertinent than studies that focused on symptomatic thrombosis. In the present viewpoint, we challenge the argument that “symptomatic” and “clinically relevant” are interchangeable. In particular, the case is made that asymptomatic events may be clinically relevant and that asymptomatic venographically detected thrombosis is a clinically relevant surrogate outcome for fatal pulmonary embolism.
Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non–Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50–1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53–2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation–related acute ischemic stroke, who started on oral anticoagulant.
Summary Previous and recent reports have suggested a fibrinolysisenhancing property of standard heparin and low molecular weight heparins, but these observations have never been confirmed in a study fulfilling appropriate methodological criteria. The aim of this study was to evaluate the effect of standard heparin and a low molecular weight heparin (Kabi 2165) on fibrinolysis in a randomized cross-over double blind placebo controlled study. Six healthy volunteers received intravenously a bolus dose of the following treatments: placebo; standard heparin, 5,000 I.U.; Kabi 2165, 5,000 anti-Xa U; Kabi 2165,10,000 anti-Xa U. Before the injection and at established times thereafter, blood samples were collected for the following assays in plasma: t-PA activity, PA inhibitor activity, fibrin plate lysis area (FPLA), plasminogen, α2-antiplasmin, fibrinogen and anti-Xa activity. Placebo and Kabi 2165, 5,000 anti-Xa U, had no effect on t-PA plasma level. Standard heparin and Kabi 2165, 10,000 anti-Xa U, produced a statistically significant increase in t-PA level at 1 hour after the infusion. This increase lasted for at least 1 hour after the infusion. No effect of any treatment on PA inhibitor, plasminogen, FLPA, α2-antiplasmin and fibrinogen was observed. We conclude that an intravenous bolus dose of both standard heparin, 5,000 I.U. and Kabi 2165, 10,000 anti-Xa U produces a delayed and sustained increase in plasma t-PA.
Clinically overt events are of obvious relevance for the outcome of patients. There is unanimous consensus of clinicians that these events should be prevented in clinical practice. In clinical trials on the prevention of deep vein thrombosis, symptomatic objectively confirmed venous thromboembolism is the most important outcome to be measured. However, because of the difficulties related to the measurement of clinically overt events, venography is the most commonly used method for end-point measurement in clinical trials on the prevention of venous thromboembolism. The limitations of venography leave a great need for the development of accurate noninvasive methods to be used as alternatives to venography. The end point must be tailored to the phase of the clinical trial. In phase I/II clinical trials, that are designed to evaluate the effectiveness of thromboprophylactic agents, it still is necessary to use the most accurate method for the diagnosis of deep vein thrombosis and to perform bilateral venography. When a new pharmacologic agent is compared with the "gold standard" agent, the use of symptomatic end points should be preferable.
