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C0255: Immediate and Long Term Mortality in Patients with Suspected Pulmonary Embolism: Prospective Cohort in Argentina
ORAL COMMUNICATIONS / Thrombosis Research 133S3 (2014) S1–S34
C0255 IMMEDIATE AND LONG TERM MORTALITY IN PATIENTS WITH SUSPECTED PULMONARY EMBOLISM: PROSPECTIVE COHORT IN ARGENTINA M.L. Posadas Martinez1 , M. Laura Martin1 , F. Gonzalez ´ Bernaldo de Quiros ´ 1 , D. Giunta1 , F. Vazquez1 . 1 Hospital Italiano de Buenos Aires, Argentina Background: The outcome of patients with suspected pulmonary embolism (SPE) in which pulmonary embolism (PE) is ruled out (RPE) is unclear. We aim to evaluate the mortality, venous thrombeoembolic disease recurrence (VTD recurrence or new VTD episode in patients RPE) and new cancer diagnosis of a cohort of patients with SPE. Methods: We designed a prospective cohort of all consecutive incident patients presenting with SPE from Emergency Department, General wards (medical and surgical) and critical care units that were included in the Institutional Registry of venous Thromboembolic disease (VTD) of the Hospital Italiano de Buenos Aires from June 2006 to March 2011. The SPE was defined by pre-specified criteria. The primary outcome was death, and a secondary outcome was any new cancer diagnosis, VTD recurrence and bleeding at follow up. Results: One thousand seven hundred thirty six cases were included for SEP and in 29% (504) PE was confirmed. There was no difference in the overall mortality at 30 days between PE and RPE (17% vs 17%, p 0.98). The presence of provoked or unprovoked risk factors in these patients did not influence mortality. In PE group, the main direct cause of death was the PE (59.5%); while neoplasm (41.8%) and sepsis (37.1%) were in RPE. Survival at one and four years was poor and similar between both groups. In multivariate analysis, age and comorbidities were independent predictors of mortality. At follow up, there was no difference in new cancer diagnosis between PE and RPE (PE 2% vs RPE 2%, p 0.82). Bleeding (7% vs 2%, p < 0.0001) and new VTD episode RPE (11% vs 5%, p < 0.0001) was most frequent in PE patients. Conclusions: The SEP is a very common situation and has poor prognosis regardless of confirming PE. The high mortality at 4 years in SPE was mainly related to comorbidities and underlying disease and not to the diagnosis of PE. C0259 PREVALENCE OF DEEP VENOUS THROMBOSIS USING BILATERAL LEG ULTRASOUND IN HOSPITALIZED PATIENTS EVALUATED FOR PULMONARY EMBOLISM? A PRELIMINARY REPORT M.L. Posadas Mart´ınez1 , D. Giunta1 , S. Sevilla2 , F. Bernaldo de Quiros1 , E. Gandara3 , V. Cubilla1 , F. Vazquez1 . 1 Hospital Italiano de Buenos Aires, Argentina; 2 Hospital Austral, Argentina; 3 Thrombosis research Institute, Ottawa, Canada Background: In outpatients with suspected PE a normal multislice CT angiography (CTPA) result safely rule out PE without the need for additional leg ultrasonography (US), but this approach has not been validated in patients who develop symptoms compatible with PE during hospitalization. We estimate prevalence of both proximal and distal deep vein thrombosis (DVT) in hospitalized patients with suspected pulmonary embolism (SPE) and the clinical utility of a whole leg US. Methods: Prospective cohort. Patients were eligible to participate in the study if they developed symptoms compatible with PE after >48 hours being admitted to the hospital for any medical reason other than SPE; or >24 hours after being admitted for surgical intervention. All patients were evaluated with CTPA (Aquilion, Toshiba). Patients were excluded if they had symptoms compatible with PE prior to admission. Within 24 hours of providing written consent, all patients had a bilateral whole leg US. The study faced a slowdown in recruitment, so an interim analysis was planned.
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Results: Between November 2011 to December 2013, 75 hospitalized patients with suspected PE (46% had active malignancy and 56% had major surgery) satisfied our inclusion criteria. Shortness of breath was the presenting symptom in 85.1% (95% CI 75.8– 91.2) of the patients, 23% (15.1–33.5) had symptoms of DVT and 41.8% (95% CI 24.8–45.3) were categorized as PE likely (Wells score >4); 85% were receiving pharmacological prophylaxis. The overall prevalence of PE (one had single subsegmental PE) was 34.6% (95% CI 24.6–45.9), with a prevalence of PE of 13.2% (95% CI 5.9–24.3) in those classified as PE unlikely. The overall prevalence of proximal DVT was 16.5% (95% CI 9.3–25.5) and 2.4% (0.4–7.9%) had distal isolated DVT. In those with PE the prevalence of proximal DVT was 39.2% (95% CI 22.6–58) vs. 6.8% (95% CI 2.3–18.1) in those without PE; whereas theprevalence of isolated distal DVT 2.4% in those with PE vs. 1.8% in those without PE (p-value 0.99). In those with DVT symptoms but without PE the risk of having a proximal DVT was significantly increased (RR 12.6; 95% CI 1.4–108). Conclusions: Our interim analysis suggests that in hospitalized patients with suspected PE ruled out by negative CTPA the prevalence of DVT is high and that a bilateral CUS is required to safely exclude PE. C0304 BEMIPARIN PHARMACODYNAMICS/PHARMACOKINETICS IN YOUNG, ELDERLY AND SUBJECTS WITH RENAL IMPAIRMENT J. Mart´ınez-Gonzalez ´ 1 , S. Rico2 , M.R. Ballester2 , I. Gutierro1 , M. Borrell1 , I. Ayani1 , R.-M. Antonijoan3 , I. Gich4 , J. Fontcuberta3 . 1 Laboratorios Farmac´euticos Rovi, S.A. Madrid, Spain; 2 CIM-St Pau, Institute of Biomedical Research, Barcelona, Spain; 3 Hospital de la Santa Creu i Sant Pau. Barcelona, Spain; 4 Autonomous University of Barcelona, Pharmacology and Therapeutics, Barcelona, Spain Background: Aging and renal impairment (RI) may prolong the half-life and lead to accumulation of low molecular weight heparins. Correct dosing is critical to prevent bleeding or thrombosis. Methods: Open, parallel group, 2-stages study. Forty eight subjects received 4 prophylactic doses (3500 IU/24h) and then (after one-week washout) a single therapeutic dose (115 IU/kg): 13 young [Y] and 12 elderly [E] (>65 years) healthy volunteers, 8 mild (ClCr ≥50 and ≤80 mL/min), 7 moderate (ClCr ≥30 and <50 mL/min), and 8 severe (ClCr <30 mL/min) RI subjects. Pharmacodynamics/pharmacokinetics (PD/PK) of anti-FXa activity and the potential need for dose adjustment were evaluated. Results: Using a non-compartmental analysis, statistically significant differences were obtained in all anti-FXa parameters comparing the severe RI to Y group, as well as in the AUCs when compared to the remaining groups. By contrast, there were no significant differences in any PD/PK parameters between Y and E groups. Anti-FXa simulations after 10 consecutive daily doses of bemiparin 3500 IU predicted mean Amax = 0.59 IU/mL in subjects with severe RI and 0.33–0.39 IU/mL in the remaining groups; one severe RI subject had Amax = 0.81 IU/mL. Simulations with adjusted prophylactic doses (2500 IU/24h) predicted individual Amax <0.60 IU/mL for all severe RI volunteers (mean Amax = 0.42 IU/ml). On the other hand, anti-FXa simulations after 10 consecutive therapeutic doses predicted mean Amax = 1.22 IU/mL in severe RI and 0.89–0.98 in the rest; one volunteer from the severe RI group had Amax >2.0 IU/mL. Simulations with 75% dose adjustment (86.25 IU/kg/24h) predicted individual Amax <1.60 IU/mL for all severe RI volunteers, and the mean Amax was within the same therapeutic range obtained for the remaining groups without adjusting dose. Conclusions: Bemiparin dose adjustments are advisable in patients with severe RI, but not required in moderate or mild RI, and in elderly with preserved renal function.
C0255 IMMEDIATE AND LONG TERM MORTALITY IN PATIENTS WITH SUSPECTED PULMONARY EMBOLISM: PROSPECTIVE COHORT IN ARGENTINA M.L. Posadas Martinez1 , M. Laura Martin1 , F. Gonzalez ´ Bernaldo de Quiros ´ 1 , D. Giunta1 , F. Vazquez1 . 1 Hospital Italiano de Buenos Aires, Argentina Background: The outcome of patients with suspected pulmonary embolism (SPE) in which pulmonary embolism (PE) is ruled out (RPE) is unclear. We aim to evaluate the mortality, venous thrombeoembolic disease recurrence (VTD recurrence or new VTD episode in patients RPE) and new cancer diagnosis of a cohort of patients with SPE. Methods: We designed a prospective cohort of all consecutive incident patients presenting with SPE from Emergency Department, General wards (medical and surgical) and critical care units that were included in the Institutional Registry of venous Thromboembolic disease (VTD) of the Hospital Italiano de Buenos Aires from June 2006 to March 2011. The SPE was defined by pre-specified criteria. The primary outcome was death, and a secondary outcome was any new cancer diagnosis, VTD recurrence and bleeding at follow up. Results: One thousand seven hundred thirty six cases were included for SEP and in 29% (504) PE was confirmed. There was no difference in the overall mortality at 30 days between PE and RPE (17% vs 17%, p 0.98). The presence of provoked or unprovoked risk factors in these patients did not influence mortality. In PE group, the main direct cause of death was the PE (59.5%); while neoplasm (41.8%) and sepsis (37.1%) were in RPE. Survival at one and four years was poor and similar between both groups. In multivariate analysis, age and comorbidities were independent predictors of mortality. At follow up, there was no difference in new cancer diagnosis between PE and RPE (PE 2% vs RPE 2%, p 0.82). Bleeding (7% vs 2%, p < 0.0001) and new VTD episode RPE (11% vs 5%, p < 0.0001) was most frequent in PE patients. Conclusions: The SEP is a very common situation and has poor prognosis regardless of confirming PE. The high mortality at 4 years in SPE was mainly related to comorbidities and underlying disease and not to the diagnosis of PE. C0259 PREVALENCE OF DEEP VENOUS THROMBOSIS USING BILATERAL LEG ULTRASOUND IN HOSPITALIZED PATIENTS EVALUATED FOR PULMONARY EMBOLISM? A PRELIMINARY REPORT M.L. Posadas Mart´ınez1 , D. Giunta1 , S. Sevilla2 , F. Bernaldo de Quiros1 , E. Gandara3 , V. Cubilla1 , F. Vazquez1 . 1 Hospital Italiano de Buenos Aires, Argentina; 2 Hospital Austral, Argentina; 3 Thrombosis research Institute, Ottawa, Canada Background: In outpatients with suspected PE a normal multislice CT angiography (CTPA) result safely rule out PE without the need for additional leg ultrasonography (US), but this approach has not been validated in patients who develop symptoms compatible with PE during hospitalization. We estimate prevalence of both proximal and distal deep vein thrombosis (DVT) in hospitalized patients with suspected pulmonary embolism (SPE) and the clinical utility of a whole leg US. Methods: Prospective cohort. Patients were eligible to participate in the study if they developed symptoms compatible with PE after >48 hours being admitted to the hospital for any medical reason other than SPE; or >24 hours after being admitted for surgical intervention. All patients were evaluated with CTPA (Aquilion, Toshiba). Patients were excluded if they had symptoms compatible with PE prior to admission. Within 24 hours of providing written consent, all patients had a bilateral whole leg US. The study faced a slowdown in recruitment, so an interim analysis was planned.
S33
Results: Between November 2011 to December 2013, 75 hospitalized patients with suspected PE (46% had active malignancy and 56% had major surgery) satisfied our inclusion criteria. Shortness of breath was the presenting symptom in 85.1% (95% CI 75.8– 91.2) of the patients, 23% (15.1–33.5) had symptoms of DVT and 41.8% (95% CI 24.8–45.3) were categorized as PE likely (Wells score >4); 85% were receiving pharmacological prophylaxis. The overall prevalence of PE (one had single subsegmental PE) was 34.6% (95% CI 24.6–45.9), with a prevalence of PE of 13.2% (95% CI 5.9–24.3) in those classified as PE unlikely. The overall prevalence of proximal DVT was 16.5% (95% CI 9.3–25.5) and 2.4% (0.4–7.9%) had distal isolated DVT. In those with PE the prevalence of proximal DVT was 39.2% (95% CI 22.6–58) vs. 6.8% (95% CI 2.3–18.1) in those without PE; whereas theprevalence of isolated distal DVT 2.4% in those with PE vs. 1.8% in those without PE (p-value 0.99). In those with DVT symptoms but without PE the risk of having a proximal DVT was significantly increased (RR 12.6; 95% CI 1.4–108). Conclusions: Our interim analysis suggests that in hospitalized patients with suspected PE ruled out by negative CTPA the prevalence of DVT is high and that a bilateral CUS is required to safely exclude PE. C0304 BEMIPARIN PHARMACODYNAMICS/PHARMACOKINETICS IN YOUNG, ELDERLY AND SUBJECTS WITH RENAL IMPAIRMENT J. Mart´ınez-Gonzalez ´ 1 , S. Rico2 , M.R. Ballester2 , I. Gutierro1 , M. Borrell1 , I. Ayani1 , R.-M. Antonijoan3 , I. Gich4 , J. Fontcuberta3 . 1 Laboratorios Farmac´euticos Rovi, S.A. Madrid, Spain; 2 CIM-St Pau, Institute of Biomedical Research, Barcelona, Spain; 3 Hospital de la Santa Creu i Sant Pau. Barcelona, Spain; 4 Autonomous University of Barcelona, Pharmacology and Therapeutics, Barcelona, Spain Background: Aging and renal impairment (RI) may prolong the half-life and lead to accumulation of low molecular weight heparins. Correct dosing is critical to prevent bleeding or thrombosis. Methods: Open, parallel group, 2-stages study. Forty eight subjects received 4 prophylactic doses (3500 IU/24h) and then (after one-week washout) a single therapeutic dose (115 IU/kg): 13 young [Y] and 12 elderly [E] (>65 years) healthy volunteers, 8 mild (ClCr ≥50 and ≤80 mL/min), 7 moderate (ClCr ≥30 and <50 mL/min), and 8 severe (ClCr <30 mL/min) RI subjects. Pharmacodynamics/pharmacokinetics (PD/PK) of anti-FXa activity and the potential need for dose adjustment were evaluated. Results: Using a non-compartmental analysis, statistically significant differences were obtained in all anti-FXa parameters comparing the severe RI to Y group, as well as in the AUCs when compared to the remaining groups. By contrast, there were no significant differences in any PD/PK parameters between Y and E groups. Anti-FXa simulations after 10 consecutive daily doses of bemiparin 3500 IU predicted mean Amax = 0.59 IU/mL in subjects with severe RI and 0.33–0.39 IU/mL in the remaining groups; one severe RI subject had Amax = 0.81 IU/mL. Simulations with adjusted prophylactic doses (2500 IU/24h) predicted individual Amax <0.60 IU/mL for all severe RI volunteers (mean Amax = 0.42 IU/ml). On the other hand, anti-FXa simulations after 10 consecutive therapeutic doses predicted mean Amax = 1.22 IU/mL in severe RI and 0.89–0.98 in the rest; one volunteer from the severe RI group had Amax >2.0 IU/mL. Simulations with 75% dose adjustment (86.25 IU/kg/24h) predicted individual Amax <1.60 IU/mL for all severe RI volunteers, and the mean Amax was within the same therapeutic range obtained for the remaining groups without adjusting dose. Conclusions: Bemiparin dose adjustments are advisable in patients with severe RI, but not required in moderate or mild RI, and in elderly with preserved renal function.