Marc F. Durian

Performance of 4 Clinical Decision Rules in the Diagnostic Management of Acute Pulmonary Embolism: A Prospective Cohort Study

BACKGROUND Several clinical decision rules (CDRs) are available to exclude acute pulmonary embolism (PE), but they have not been directly compared. OBJECTIVE To directly compare the performance of 4 CDRs (Wells rule, revised Geneva score, simplified Wells rule, and simplified revised Geneva score) in combination with d-dimer testing to exclude PE. DESIGN Prospective cohort study. SETTING 7 hospitals in the Netherlands. PATIENTS 807 consecutive patients with suspected acute PE. INTERVENTION The clinical probability of PE was assessed by using a computer program that calculated all CDRs and indicated the next diagnostic step. Results of the CDRs and d-dimer tests guided clinical care. MEASUREMENTS Results of the CDRs were compared with the prevalence of PE identified by computed tomography or venous thromboembolism at 3-month follow-up. RESULTS Prevalence of PE was 23%. The proportion of patients categorized as PE-unlikely ranged from 62% (simplified Wells rule) to 72% (Wells rule). Combined with a normal d-dimer result, the CDRs excluded PE in 22% to 24% of patients. The total failure rates of the CDR and d-dimer combinations were similar (1 failure, 0.5% to 0.6% [upper-limit 95% CI, 2.9% to 3.1%]). Even though 30% of patients had discordant CDR outcomes, PE was not detected in any patient with discordant CDRs and a normal d-dimer result. LIMITATION Management was based on a combination of decision rules and d-dimer testing rather than only 1 CDR combined with d-dimer testing. CONCLUSION All 4 CDRs show similar performance for exclusion of acute PE in combination with a normal d-dimer result. This prospective validation indicates that the simplified scores may be used in clinical practice. PRIMARY FUNDING SOURCE Academic Medical Center, VU University Medical Center, Rijnstate Hospital, Leiden University Medical Center, Maastricht University Medical Center, Erasmus Medical Center, and Maasstad Hospital.

Hestia criteria can safely select patients with pulmonary embolism for outpatient treatment irrespective of right ventricular function.

There has been debate over how patients with pulmonary embolism (PE) can be safely selected for outpatient treatment.

Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma.

The combination of melphalan, prednisone, and thalidomide (MPT) is considered standard therapy for newly diagnosed patients with multiple myeloma who are ineligible for stem cell transplantation. Long-term treatment with thalidomide is hampered by neurotoxicity. Melphalan, prednisone, and lenalidomide, followed by lenalidomide maintenance therapy, showed promising results without severe neuropathy emerging. We randomly assigned 668 patients between nine 4-week cycles of MPT followed by thalidomide maintenance until disease progression or unacceptable toxicity (MPT-T) and the same MP regimen with thalidomide being replaced by lenalidomide (MPR-R). This multicenter, open-label, randomized phase 3 trial was undertaken by Dutch-Belgium Cooperative Trial Group for Hematology Oncology and the Nordic Myeloma Study Group (the HOVON87/NMSG18 trial). The primary end point was progression-free survival (PFS). A total of 318 patients were randomly assigned to receive MPT-T, and 319 received MPR-R. After a median follow-up of 36 months, PFS with MPT-T was 20 months (95% confidence interval [CI], 18-23 months) vs 23 months (95% CI, 19-27 months) with MPR-R (hazard ratio, 0.87; 95% CI, 0.72-1.04; P = .12). Response rates were similar, with at least a very good partial response of 47% and 45%, respectively. Hematologic toxicity was more pronounced with MPR-R, especially grades 3 and 4 neutropenia: 64% vs 27%. Neuropathy of at least grade 3 was significantly higher in the MPT-T arm: 16% vs 2% in MPR-R, resulting in a significant shorter duration of maintenance therapy (5 vs 17 months in MPR-R), irrespective of age. MPR-R has no advantage over MPT-T concerning efficacy. The toxicity profile differed with clinically significant neuropathy during thalidomide maintenance vs myelosuppression with MPR.

Thromboembolic resolution assessed by CT pulmonary angiography after treatment for acute pulmonary embolism

The systematic assessment of residual thromboembolic obstruction after treatment for acute pulmonary embolism (PE) has been understudied. This assessment is of potential clinical importance, should clinically suspected recurrent PE occur, or as tool for risk stratification of cardiopulmonary complications or recurrent venous thromboembolism (VTE). This study aimed to assess the rate of PE resolution and its implications for clinical outcome. In this prospective, multi-center cohort study, 157 patients with acute PE diagnosed by CT pulmonary angiography (CTPA) underwent follow-up CTPA-imaging after six months of anticoagulant treatment. Two expert thoracic radiologists independently assessed the presence of residual thromboembolic obstruction. The degree of obstruction at baseline and follow-up was calculated using the Qanadli obstruction index. All patients were followed-up for 2.5 years. At baseline, the median obstruction index was 27.5 %. After six months of treatment, complete PE resolution had occurred in 84.1 % of the patients (95 % confidence interval (CI): 77.4-89.4 %). The median obstruction index of the 25 patients with residual thrombotic obstruction was 5.0 %. During follow-up, 16 (10.2 %) patients experienced recurrent VTE. The presence of residual thromboembolic obstruction was not associated with recurrent VTE (adjusted hazard ratio: 0.92; 95 % CI: 0.2-4.1).This study indicates that the incidence of residual thrombotic obstruction following treatment for PE is considerably lower than currently anticipated. These findings, combined with the absence of a correlation between residual thrombotic obstruction and recurrent VTE, do not support the routine use of follow-up CTPA-imaging in patients treated for acute PE.

Hestia criteria can discriminate high- from low-risk patients with pulmonary embolism

We investigated whether the clinical criteria used in the Hestia study for selection of pulmonary embolism (PE) patients for outpatient treatment could discriminate PE patients with high and low risk for adverse clinical outcome. We performed a cohort study with PE patients who were triaged with 11 criteria for outpatient treatment. Patients not eligible for outpatient treatment were treated in hospital. Study outcomes were recurrent venous thromboembolism, major bleeding and all-cause mortality during 3 months. In total, 530 patients were included, of which 297 were treated at home. In the outpatient group, six patients (2.0%, 95% CI 0.7–4.3%) had recurrent venous thromboembolism versus nine in-patients (3.9%, 95% CI 1.9–7.0%). Three patients (1.0%, 95% CI 0.2–2.9) died during the 3-months follow-up in the outpatient group versus 22 patients (9.6%, 95% CI 6.3–14) in the in-patient group (p<0.05). None of the outpatients died as a result of fatal PE versus five (2.2%) in-patients (p<0.05). In the outpatient group, 0.7% (95% CI 0.08–2.4) had major bleeding events versus 4.8% (95% CI 2.4–8.4) of in-patients (p<0.05). This study showed that the Hestia criteria can discriminate PE patients with low risk from patients with high risk for adverse clinical outcome. The low-risk patients can safely be treated at home.