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Victor F. Tapsonopoulos, MD, FCCP, FRCP Professor of Medicine Director, Center for Pulmonary Vascular Disease Division of Pulmonary and Critical Care Duke University Medical Center Durham, N.C. USA Does PE Alter the Management and Outcome in Patients with DVT?

Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

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Page 1: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Victor F. Tapsonopoulos, MD, FCCP, FRCP

Professor of Medicine

Director, Center for Pulmonary Vascular

Disease

Division of Pulmonary and Critical Care

Duke University Medical Center

Durham, N.C. USA

Does PE Alter the Management and Outcome in

Patients with DVT?

Page 2: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Disclosure

Victor Tapson, M.D., FACCP

I disclose the following financial relationship(s):

•Research Grant: Bayer, Johnson & Johnson, Sanofi-

Aventis;

•Consultant/Advisory Board: Sanofi-Aventis

Page 3: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Risk of Fatal PE in Patients with Treated VTE

Objective:

To provide reliable estimates of the risk of fatal PE and the case-fatality rate of recurrent DVT or PE among patients presenting with symptomatic DVT or PE, during and following 3 months of anticoagulant therapy.

Data Sources:

A MEDLINE literature search was performed to identify prospective studies in which patients with symptomatic DVT or PE were treated with 5 to 10 days of heparin and 3 months of oral therapy. We searched 1966 to Sept. 1997; Current Contents / bibliographies also scanned.

Data Extraction:

Of 137 retrieved studies, 25 studies satisfied predetermined methodologic criteria and were included in the analysis.

Douketis JD, et al. JAMA 1998;279:458-462.

Page 4: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Results: Risk of Fatal PE in Patients with Treated VTE

Patients presenting with DVT were more likely to recur

as DVT (78.6%) rather than PE (21.4%), whereas

patients presenting with PE were more likely to recur

with PE (81.1%) than DVT (18.9%).

Among patients presenting with DVT, the case-fatality

rate of recurrent DVT or PE during anticoagulation was

8.8% (95% CI, 5.0%-14.1%). Following anticoagulant

therapy it was 5.1% (95% CI, 1.4%-12.5%).

Among patients presenting with PE, the case-fatality rate

of recurrent DVT or PE was 26.4% (95% CI, 16.7%-

38.1%).*

*If possible PE deaths were included, it was 36.1% (30/83).

Douketis JD, et al. JAMA 1998;279:458-462.

Page 5: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Conclusions:

Patients presenting with acute DVT were more likely to have DVT as a manifestation of recurrent VTE, whereas patients presenting with PE were more likely to have recurrent PE as a manifestation of recurrent VTE.

Patients presenting with PE are more likely to die of recurrent PE than are patients presenting with DVT.

Risk of Fatal PE in Patients with Treated VTE

Douketis JD, et al. JAMA 1998;279:458-462.

Page 6: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Calf vein DVT – extends into politeal

Page 7: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Segmental level embolism

Page 8: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and
Page 9: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Silent PE in Patients with DVT:

A Systematic Review

Methods

28 published studies were identified through PubMed.

Studies were selected if methods of diagnosis of PE were

described; if PE was stated to be asymptomatic; and if

raw data were presented.

Studies were stratified according to whether silent PE was

diagnosed by a high-probability VQ scan (PIOPED), CTA

or conventional PAG (Tier 1), or by lung scans based on

non-PIOPED criteria (Tier 2).

Stein PD, et al. Am J Med 2010;123:426-31

Page 10: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Silent PE in Patients with DVT:

A Systematic Review

Results

Silent PE was diagnosed in 1665 of 5233 patients (32%)

with DVT.

The incidence of silent PE was higher with proximal DVT

than with distal DVT.

25/488 (5.1%) with silent PE versus 7/1093 (0.6%)

without silent PE had recurrent PE.

Stein PD, et al. Am J Med 2010;123:426-31

Page 11: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Silent PE in Patients with DVT:

A Systematic Review

Results

Silent PE was diagnosed in 1665 of 5233 patients (32%)

with DVT.

The incidence of silent PE was higher with proximal DVT

than with distal DVT.

25/488 (5.1%) with silent PE versus 7/1093 (0.6%)

without silent PE had recurrent PE.

Stein PD, et al. Am J Med 2010;123:426-31

Page 12: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Silent PE in Patients with DVT:

A Systematic Review

Conclusion

Silent PE sometimes involved central pulmonary arteries.

Because approximately one-third of patients with DVT have silent PE, routine screening for PE may be advantageous.

Silent PE appeared to increase the risk of recurrent PE.

Stein PD, et al. Am J Med 2010;123:426-31

Page 13: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Diagnosis of PE in Patients with Proximal DVT:

Specificity of Symptoms and Perfusion Defects at Baseline

and during Anticoagulant TherapySensitivity and specificity of symptoms for PE were 74 and 67%, respectively.

Among 37 patients with symptoms and nondiagnostic lung scans, only 8 (22%) had PE at angiography.

Repeated perfusion studies with comparison to baseline tests excluded PE in 21 cases.

Cumulated 3-mo risks of suspected and confirmed PE were 6.8% (95% CI, 5.4- 8.2%) and 2.0% (95% CI, 0.6-3.4%) respectively.

Even in patients with known proximal DVT, PE symptoms are nonspecific and careful imaging is needed for diagnosis, at baseline and during anticoagulant therapy.

Girard P, et al. AJRCCM 2001;164:1033-1037

Page 14: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Systematic Lung Scans Reveal a High Frequency of

Silent PE in Patients With Proximal DVT

Meignan M, et al. Arch Intern Med. 2000;160:159-164.

Background A high frequency of asymptomatic PE has been reported

in patients with DVT in studies of a limited number of patients using

varying criteria for lung scan assessment.

Objectives To estimate the frequency of PE using systematic lung

scans in a large group of outpatients with DVT and to compare results

using varying lung scan assessment criteria.

Methods An international multicenter study comparing 2 different

regimens of nadroparin in DVT: perfusion lung scans were performed in

622 outpatients with no clinical indication of PE and with proximal DVT

confirmed by venography.

379 of these patients underwent ventilation lung scans.

High-probability (HP) scans for PE were assessed separately using

either ventilation scans or chest radiographs to define mismatched

perfusion defects.

Page 15: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Systematic Lung Scans Reveal a High Frequency of Silent Pulmonary

Embolism in Patients With Proximal Deep Venous Thrombosis

Meignan M, et al. Arch Intern Med. 2000;160:159-164.

Results

Depending on the criteria used, 32% to 45% had HP scans for PE; these percentages were higher in young patients.

No relationship found between extent of thrombosis and HP scans.

The estimated frequency of silent PE was 39.5% to 49.5%.

During 3-mo. f/u period while patients received therapy, the rate of PE recurrence was low (1.3%) and did not differ between patients with baseline HP scans and those with normal scans.

Conclusions

Regardless of what interpretative criteria are used for assessing lung scans in PE, the frequency of silent PE is 40% to 50% in patients with DVT.

A baseline lung scan may easily detect PE in these patients but is not useful for predicting early thromboembolic recurrences that may occur during therapy.

Page 16: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Systematic Lung Scans Reveal a High Frequency of Silent Pulmonary

Embolism in Patients With Proximal Deep Venous Thrombosis

Meignan M, et al. Arch Intern Med. 2000;160:159-164.

Results

Depending on the criteria used, 32% to 45% had HP scans for PE; these percentages were higher in young patients.

No relationship found between extent of thrombosis and HP scans.

The estimated frequency of silent PE was 39.5% to 49.5%.

During 3-mo. f/u period while patients received therapy, the rate of PE recurrence was low (1.3%) and did not differ between patients with baseline HP scans and those with normal scans.

Conclusions

Regardless of what interpretative criteria are used for assessing lung scans in PE, the frequency of silent PE is 40% to 50% in patients with DVT.

A baseline lung scan may easily detect PE in these patients but is not useful for predicting early thromboembolic recurrences that may occur during therapy.

Page 17: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Systematic Lung Scans Reveal a High Frequency of Silent Pulmonary

Embolism in Patients With Proximal Deep Venous Thrombosis

Meignan M, et al. Arch Intern Med. 2000;160:159-164.

Results

Depending on the criteria used, 32% to 45% had HP scans for PE; these percentages were higher in young patients.

No relationship found between extent of thrombosis and HP scans.

The estimated frequency of silent PE was 39.5% to 49.5%.

During 3-mo. f/u period while patients received therapy, the rate of PE recurrence was low (1.3%) and did not differ between patients with baseline HP scans and those with normal scans.

Conclusions

Regardless of what interpretative criteria are used for assessing lung scans in PE, the frequency of silent PE is 40% to 50% in patients with DVT.

A baseline lung scan may easily detect PE in these patients but is not useful for predicting early thromboembolic recurrences that may occur during therapy.

Page 18: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Relationship Between the Extent of DVT and

the Extent of Acute PE as Assessed by CT

Angiography

Although PE occurs in a majority of patients with

DVT, and vice versa, the amount/burden of clot

load in one condition does not necessarily

indicate — or indicates only weakly — the

degree of burden in the other condition.

Ghaye B, et al. British Journal of Radiology 2009;82:198-203

Page 19: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Rationale: Concomitant DVT in patients with acute PE has an uncertain prognostic significance.

Objectives: In a cohort of patients with PE, this study compared the risk of death in those with and those without concomitant DVT.

Methods: We conducted a prospective cohort study of outpatients diagnosed with a 1st episode of acute symptomatic PE. Patients underwent bilateral leg venous US to assess for concomitant DVT.

The primary study outcome, all-cause mortality, and the secondary outcome of PE-specific mortality were assessed during 3 mos. of follow-up after PE diagnosis.

Jiménez D, et al, and the RIETE investigators. AJRCCM 2010;181:983-991.

Prognostic Significance of DVT in Patients Presenting with Acute Symptomatic PE

Page 20: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Measurements and Main Results:

Multivariate Cox proportional hazards regression was done to adjust for significant covariates.

Of 707 patients diagnosed with PE, 51.2% (362 of 707) had concomitant DVT and 10.9% (77 of 707) died during follow-up.

Patients with concomitant DVT had an increased all-cause mortality (adjusted HR, 2.05; 95% CI, 1.24 to 3.38; P = 0.005) and PE-specific mortality (adjusted HR, 4.25; 95% CI, 1.61 to 11.25; P = 0.04) compared with those without concomitant DVT.

In an external validation cohort of 4,476 patients with acute PE enrolled in the RIETE Registry, concomitant DVT remained a significant predictor of both all-cause mortality (adjusted HR, 1.66; 95% CI, 1.28 to 2.15; P < 0.001) and PE-specific mortality (adjusted HR, 2.01; 95% CI, 1.18 to 3.44; P = 0.01).

Jiménez D, et al, and the RIETE investigators. AJRCCM 2010;181:983-991.

Prognostic Significance of DVT in Patients Presenting with Acute Symptomatic PE

Page 21: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Conclusions:

In patients with a first episode of acute

symptomatic PE, the presence of concomitant

DVT is an independent predictor of death in the

ensuing 3 months after diagnosis. Assessment

of the thrombotic burden should assist with risk

stratification of patients with acute PE.

Jiménez D, et al, and the RIETE investigators. AJRCCM 2010;181:983-991.

Prognostic Significance of DVT in Patients Presenting with Acute Symptomatic PE

Page 22: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Effect of DVT on PE PrognosisA. VitarelliEchocardiography, troponins and lower extremity ultrasound: the 'Three Musketeers' lead the prognosis of acute pulmonary embolismThorax, January 1, 2011; 66: 2 - 4.

D. Jimenez, D. Aujesky, L. Moores, V. Gomez, D. Marti, S. Briongos, M. Monreal, V. Barrios, S. Konstantinides, and R. D. YusenCombinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolismThorax, January 1, 2011; 66: 75 - 81.

D. JimenezPrognostication of Pulmonary Embolism: Not Just a Matter of the HeartAm. J. Respir. Crit. Care Med., November 1, 2010; 182: 1096 - 1097.

M. Miniati and S. MontiPrognostic Significance of Deep Vein Thrombosis in Acute Pulmonary EmbolismAm. J. Respir. Crit. Care Med., September 15, 2010; 182: 855 - 855.

D. Jimenez, R. D. Yusen, and on behalf of all coauthorsMortality-Risk Profiling using Doppler Leg Scans in Patients with Pulmonary EmbolismAm. J. Respir. Crit. Care Med., September 15, 2010; 182: 856 - 857.

N. Ahmad, K. Srinivasan, and H. MoudgilMortality-Risk Profiling using Doppler Leg Scans in Patients with Pulmonary EmbolismAm. J. Respir. Crit. Care Med., September 15, 2010; 182: 855 - 856.

Significance of Detectable Deep Venous Thrombosis in Patients with Pulmonary EmbolismJournal Watch (General), May 13, 2010; : 5 - 5.

Page 23: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

What about incidental PE?

Page 24: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Incidental discovery of PE: Treat?

Page 25: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Incidental PE: Underdiagnosis or Overdiagnosis?

Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med 2011 XXXX

Auer RC, Schulman AR, Tuorto S, et al. Use of helical CT is associated with an increased incidence of postoperative pulmonary emboli in cancer patients with no change in the number of fatal pulmonary emboli. J Am Coll Surg 2009;208:871-8.

Burge AJ, Freeman KD, Klapper PJ, Haramati LB. Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clin Radiol 2008;63:381-386.

Carrier M, Righini M, Wells PS, et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. J Thromb Haemost 2010;8:1716-22.

Donato AA, Khoche S, Santora J, Wagner B. Clinical outcomes in patients with isolated subsegmental pulmonary emboli diagnosed by multidetector CT pulmonary angiography. Thromb Res 2010. Oct;126(4):e266-70.

Cronin CG, Lohan DG, Keane M, Roche C, Murphy JM. Prevalence and significance of asymptomatic venous thromboembolic disease found on oncologic staging CT. AJR 2007;189:162-70.

O’Connell CL, Boswell WD, Duddalwar V, et al. Unsuspected pulmonary emboli in cancer patients: clinical correlates and relevance. J Clin Oncol 2006;24:4928-4932.

Page 26: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Incidental PE: Underdiagnosis or Overdiagnosis?

Wiener RS, Schwartz LM, Woloshin S. Time trends in pulmonary embolism in the United States: evidence of overdiagnosis. Arch Intern Med 2011 XXXX

Auer RC, Schulman AR, Tuorto S, et al. Use of helical CT is associated with an increased incidence of postoperative pulmonary emboli in cancer patients with no change in the number of fatal pulmonary emboli. J Am Coll Surg 2009;208:871-8.

Burge AJ, Freeman KD, Klapper PJ, Haramati LB. Increased diagnosis of pulmonary embolism without a corresponding decline in mortality during the CT era. Clin Radiol 2008;63:381-386.

Carrier M, Righini M, Wells PS, et al. Subsegmental pulmonary embolism diagnosed by computed tomography: incidence and clinical implications. A systematic review and meta-analysis of the management outcome studies. J Thromb Haemost 2010;8:1716-22.

Donato AA, Khoche S, Santora J, Wagner B. Clinical outcomes in patients with isolated subsegmental pulmonary emboli diagnosed by multidetector CT pulmonary angiography. Thromb Res 2010. Oct;126(4):e266-70.

Cronin CG, Lohan DG, Keane M, Roche C, Murphy JM. Prevalence and significance of asymptomatic venous thromboembolic disease found on oncologic staging CT. AJR 2007;189:162-70.

O’Connell CL, Boswell WD, Duddalwar V, et al. Unsuspected pulmonary emboli in cancer patients: clinical correlates and relevance. J Clin Oncol 2006;24:4928-4932.

Page 27: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Chronic Thromboembolic

Pulmonary Hypertension

Page 28: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and
Page 29: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

ConclusionsPatients presenting with acute DVT are more likely to recur with DVT whereas patients presenting with acute PE are more likely to recur with PE.

Patients presenting with PE are more likely to die of recurrent PE than are patients presenting with DVT.

Regardless of interpretative criteria used for assessing lung scans in PE, the frequency of silent PE is 40% to 50% in patients with DVT.

In one trial, silent PE appeared to increase risk of recurrent PE, in another, in patients with proximal DVT, risk of recurrence was low.

Even in patients with known proximal DVT, PE symptoms are nonspecific and careful imaging is needed for diagnosis at baseline and during therapy.

In patients with a first episode of acute symptomatic PE, the presence of concomitant DVT is an independent predictor of death in the ensuing 3 months after diagnosis. Assessment of the thrombotic burden should assist with risk stratification of patients with acute PE.

Page 30: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

Postphlebitic syndrome’s a pain

In the figurative and literal vein.

If you hurt and you swell

You can’t clinically tell

If it’s new clot or more of the same

-VFT

Page 31: Does PE Alter the Management and Outcome in Patients with DVT? · Risk of Fatal PE in Patients with Treated VTE Objective: To provide reliable estimates of the risk of fatal PE and

THANK YOU!!