Comparison of All-Cause Mortality Following VTE Treatment Between Propensity Score-Adjusted Observational Studies and Matched Randomized Controlled Trials: Meta-Epidemiologic Study.

BACKGROUND: It is unknown whether propensity score-adjusted observational studies produce results comparable to those of randomized controlled trials (RCTs) that address similar VTE treatment issues. METHODS: The PubMed and Web of Science databases were systematically searched for propensity score-adjusted observational studies, RCTs, and meta-analyses of RCTs that estimated all-cause mortality following VTE treatment. After identifying distinct clinical treatment issues evaluated in the eligible observational studies, a standardized algorithm was used to identify and match at least one RCT or RCT meta-analysis publication for paired study design analyses. Meta-analyses were used to summarize groups of studies. Treatment efficacy statistics (relative ORs) were compared between the paired observational and RCT studies, and the summary relative ORs for all study design pairs were also calculated. RESULTS: The observational and RCT study pairs assessed seven clinical treatment issues. Overall, the observational study-RCT pairs did not exhibit significantly different mortality estimates (summary relative OR, 0.89; 95% CI, 0.32-1.46; I2 = 23%). However, two of the seven treatment issue study pairs (thrombolysis vs anticoagulation for pulmonary embolism; once- vs twice-daily enoxaparin for VTE) exhibited a significantly different treatment effect direction, and there was a substantial (nonsignificant) difference in the magnitude of the effect in another two of the study pairs (rivaroxaban vs vitamin K antagonists for VTE; home treatment vs hospitalization for DVT). CONCLUSIONS: This systematic comparison across seven VTE treatment topics suggests that propensity score-adjusted observational studies and RCTs often exhibit similar all-cause mortality, although differences in the direction or the magnitude of estimated treatment effects may occasionally occur. TRIAL REGISTRY: PROSPERO; CRD42018087819; URL: http://www.crd.york.ac.uk/PROSPERO.

Meta-Analysis of Prevalence and Short-Term Prognosis of Hemodynamically Unstable Patients With Symptomatic Acute Pulmonary Embolism.

There remains limited information about the prevalence and outcomes of hemodynamic unstable patients with acute pulmonary embolism (PE). We performed a systematic review and meta-analysis of prospective registries that enrolled patients with acute PE to assess the prevalence and prognostic significance of hemodynamic instability for the primary outcome of short-term all-cause mortality, and the secondary outcome of short-term PE-related mortality. We also assessed the association between use of thrombolytic therapy versus no use and short-term outcomes in the subgroup of unstable patients. We used a random-effects model to pool study results; and I2 testing to assess for heterogeneity. The authors' search retrieved 4 studies that enrolled 1,574 patients with unstable PE (1,574/40,363; 3.9%; 95% confidence interval [CI], 3.7% to 4.1%). Hemodynamic instability had a significant association with short-term all-cause mortality (odds ratio [OR], 5.9; 95% CI, 2.7 to 13.0; I2 = 94%), and with PE-related death (OR, 8.2; 95% CI, 3.4 to 19.7). In unstable patients, thrombolytic therapy was associated with reduced odds of short-term all-cause mortality (OR, 0.69; 95% CI, 0.49 to 0.95), and PE-related death (OR, 0.66; 95% CI, 0.45 to 0.97). In conclusion, hemodynamic instability significantly increased the risk of death shortly after PE diagnosis. Use of thrombolytic therapy was associated with significantly reduced short-term mortality.

Accuracy and Interobserver Reliability of the Simplified Pulmonary Embolism Severity Index Versus the Hestia Criteria for Patients With Pulmonary Embolism.

OBJECTIVES: The objective was to assess and compare the accuracy and interobserver reliability of the simplified Pulmonary Embolism Severity Index (sPESI) and the Hestia criteria for predicting short-term mortality in patients with pulmonary embolism (PE). METHODS: This prospective cohort study evaluated consecutive eligible adults with PE diagnosed in the emergency department (ED) at a large, tertiary, academic medical center in the era January 1, 2015, to December 30, 2017. We assessed and compared sPESI and Hestia criteria prognostic accuracy for 30-day all-cause mortality after PE diagnosis and their interobserver reliability for classifying patients as low risk or high risk. Two clinician investigators scored both prediction tools during the ED evaluation. We used the kappa statistic to test for agreement. RESULTS: The 488-patient cohort had a mean (±SD) age of 69.0 (±17.1) years and an approximately even sex distribution. The investigators classified one-quarter of patients as low risk using the sPESI and Hestia criteria (28% vs. 27%, respectively). During the 30-day follow-up, 31 of the 488 (6.4%) patients died. Patients classified as low risk according to the sPESI and the Hestia criteria had a similar 30-day mortality (sPESI 0.7% [1/135], 95% confidence interval [CI] = 0.0%-4.0%; Hestia 2.3% [3/132], 95% CI = 0.5%-6.5%). The two observers had good agreement (κ = 0.80) for the Hestia criteria and very good agreement (κ = 0.97) for the sPESI. CONCLUSION: The sPESI and the Hestia criteria had similar risk classification determination and prognostic accuracy for 30-day mortality after PE. However, the succinct and more objective sPESI had higher interobserver reliability than the Hestia criteria.

Assessment of coexisting deep vein thrombosis for risk stratification of acute pulmonary embolism.

BACKGROUND: In patients with acute pulmonary embolism (PE), studies have shown an association between coexisting deep vein thrombosis (DVT) and short-term prognosis. It is not known whether complete compression ultrasound testing (CCUS) improves the risk stratification of their disease beyond the recommended prognostic models. METHODS: We included patients with normotensive acute symptomatic PE and prognosticated them with the European Society of Cardiology (ESC) risk model for PE. Subsequently, we determined the prognostic significance of coexisting DVT in patients with various ESC risk categories. The primary endpoint was a complicated course after the diagnosis of PE, defined as death from any cause, haemodynamic collapse, or adjudicated recurrent PE. RESULTS: According to the ESC model, 37% of patients were low-risk, 56% were intermediate-low risk, and 6.7% were intermediate-high risk. CCUS demonstrated coexisting DVT in 375 (44%) patients. Among the 313 patients with low-risk PE, coexisting DVT (46%) did not show a significant increased risk of complicated course (2.8%; 95% confidence interval [CI], 0.8%-7.0%), compared with those without DVT (0.6%; 95% CI, 0%-3.2%), (P = 0.18). Of the 478 patients with intermediate-low risk PE, a complicated course was 14% and 6.8% for those with and without DVT, respectively (P = 0.01). Of the 57 patients that had intermediate-high risk PE, a complicated course occurred in 17% and 18% for those with and without DVT, respectively (P = 1.0). CONCLUSIONS: In normotensive patients with PE, testing for coexisting DVT might improve risk stratification of patients at intermediate-low risk for short-term complications.

Clinical gestalt versus prognostic scores for prognostication of patients with acute symptomatic pulmonary embolism. / Evaluación clínica frente a escalas estandarizadas para el pronóstico de los pacientes con tromboembolia pulmonar aguda sintomática.

BACKGROUND AND OBJECTIVE: To determine the accuracy of clinical gestalt to identify patients with acute symptomatic pulmonary embolism (PE) at low-risk for short-term complications. PATIENTS AND METHODS: This study included a total of 154 consecutive patients diagnosed with acute symptomatic PE in a tertiary university hospital. We compared the prognostic accuracy of the Pulmonary Embolism Severity Index (PESI), the simplified PESI (sPESI), and clinical gestalt of 1) 2senior physicians (one with and one without experience in the management of patients with PE), 2) a fourth-year resident of Pneumology, 3) a third-year resident of Pneumology, and 4) a second-year resident of Pneumology. The primary outcome was all-cause mortality during the first month after the diagnosis of PE. RESULTS: Thirty-day all-cause mortality was 8.4% (13/154; 8.4%; 95% confidence interval [CI], 4.1-12.8%). The PESI and clinical gestalt classified more patients as low-risk, compared to the sPESI (36.4%, 31.3% y 28.6%, respectively). There were no deaths in the sPESI low-risk category (negative predictive value 100%). Prognostic accuracy increased with increasing experience (84.6 vs. 92.3%; P=.049). CONCLUSIONS: The sPESI showed the best accuracy at correctly identifying low-risk patients with acute symptomatic PE. Clinical gestalt is not inferior to standardized clinical prediction rules to prognosticate patients with acute PE.

Impact of obstructive sleep apnea on cardiovascular outcomes in patients with acute symptomatic pulmonary embolism: Rationale and methodology for the POPE study.

In normotensive patients with acute symptomatic pulmonary embolism (PE), the effect of undiagnosed obstructive sleep apnea (OSA) on cardiovascular (CV) outcomes lacks clarity. The Prognostic Significance of Obstructive Sleep Apnea in Patients With Acute Symptomatic Pulmonary Embolism (POPE) study is a multicenter, observational study designed to prospectively assess the prognostic significance of concomitant OSA in hemodynamically stable outpatients with acute symptomatic PE. Adult patients with acute stable PE are eligible. Recruited patients undergo an overnight sleep study using a level III portable diagnostic device within 7 days (and preferably within 48 hours) of diagnosis of PE. The sleep tracings are analyzed by a certified sleep technologist and audited by a sleep physician, both of whom are blinded to other study data. The patients are divided into 2 groups based on apnea-hypopnea index (AHI): OSA (AHI ≥15) and non-OSA (AHI <15) groups. The study uses a composite of PE-related death, CV death, clinical deterioration requiring an escalation of treatment, or nonfatal CV events (recurrent venous thromboembolism, acute myocardial infarction, or stroke) within 30 days after the diagnosis of PE as the primary outcome. The projected sample size of 225 patients will provide 80% power to test the hypothesis that OSA will increase the primary outcome from 7% in the non-OSA group to 20% in the OSA group, with α ≤0.05. The trial results will be important to understand the burden and CV effects of OSA in PE patients.