Early Anticoagulation is Associated with Reduced Mortality for Acute Pulmonary Embolism

Sean B. Smith, MD; Jeffrey B. Geske, MD; Jennifer M. Maguire, MD; Nicholas A. Zane, BA; Rickey E. Carter, PhD; Timothy I. Morgenthaler, MD, FCCP


CHEST. 2010;137(6):1382-1390. 

In This Article

Materials and Methods

Patient Selection and Characterization

We conducted a retrospective review of a cohort of adult patients who presented to a single tertiary care ED with acute PE between June 17, 2002, and September 6, 2005. All PE diagnoses were confirmed by CT scan angiography. Patients were excluded if diagnosis was prior to arrival or if anticoagulation was contraindicated. All patients were initially treated with an IV weight-based heparin nomogram similar to the one described by Raschke et al[14] as per our institutional practice. This study was approved by the Mayo Clinic Institutional Review Board.

Definitions and Data Collection

Acute PE was defined as a filling defect seen on CT scan angiography in patients presenting to the ED with symptoms consistent with pulmonary artery hypoperfusion or infarction (ie, dyspnea, chest pain, lightheadedness, and/or syncope). Patients were excluded if they had an asymptomatic PE found incidentally on a CT scan done for reasons other than the above symptoms.

Patients were characterized as having received heparin either in the ED or after admission. We used 24 h as a discriminating timeframe for achieving a therapeutic aPTT because this has been a validated clinical timeframe in previous studies.[14,15] Primary outcomes were in-hospital and 30-day all-cause mortality. Secondary outcomes were hospital and ICU lengths-of-stay, hemorrhagic events on heparin, and recurrent VTE within 90 days.

The medical record was reviewed to determine length of follow-up and time to death. Hospital length-of-stay was determined by the earliest time documented upon ED arrival and the time when the hospital summary was signed on the discharge day. The time of heparinization was determined by review of documentation from ED or admitting physicians and the drug administration records as available. Laboratory draw times were reviewed to determine the interval between arrival and the first therapeutic aPTT, which was defined as 1.5 times the baseline aPTT or at least 50 s. A hemorrhagic event on IV heparin was defined as acute blood loss of at least 2 g of hemoglobin that required cessation of heparin and transfusion. Recurrent VTE was defined as a documented DVT or PE within 90 days of initial presentation.

Demographic data, presenting vital signs, and laboratory values were cataloged, and a Wells score for PE was calculated for each patient in the standard fashion.[19,20] In order to calculate the Wells score, we reviewed documentation to determine if a diagnosis other than PE was considered more or less likely. Comorbidities considered were history of VTE or coagulopathy, active malignancy, COPD, coronary artery disease (CAD), congestive heart failure (CHF), or active nicotine use. Tachycardia was defined as a heart rate > 100 beats per minute, hypotension as a systolic BP (SBP) < 100 mm Hg, leukocytosis as a WBC count > 10 × 109 cells/mL, a positive troponin T as > 0.01 ng/mL, and a positive d-dimer as > 500 ng/mL.

Data Analysis

Median values are reported with interquartile ranges (IQR) because data were not normally distributed. Fisher exact and Student t tests were used to compare the frequency of baseline demographics and comorbidities. Odds ratios (OR) were calculated for categorical variables based on χ2 analyses, and OR for a one-unit change in continuous variables were estimated using logistic regression. Ninety-five percent CIs are reported. The type 1 error rate was set at 0.05 (two-side) a priori, and no correction factor has been applied to reported P values to account for multiple comparison issues.

Because patients were not randomized, propensity scores for the likelihood of receiving heparin in the ED or achieving a therapeutic aPTT within 24 h were calculated. Propensity scores were calculated in a multiple logistic regression model including the following 17 factors: age, gender, heart rate, SBP nicotine use, CAD, CHF, COPD, oral contraceptive use, coagulation disorder, history of previous VTE, malignancy, hemoptysis, recent surgery or immobility (within 30 days prior to presentation), Wells score, leukocyte count, and whether an alternative diagnosis was less likely. The estimated propensity score was used as a covariate in multiple logistic regression models.

Kaplan-Meier curves were created to compare the times from arrival to therapeutic aPTT for the survivor and nonsurvivor populations. Given the limited number of in-hospital deaths, multiple logistic regression modeling was performed only for 30-day mortality in order to avoid an over-fit in-hospital model. Data were analyzed with JMP 8.0 (2008; SAS Institute Inc.; Cary, NC). Statistical analyses were aided by the Center for Translational Science Activities at our institution.


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