Alejandro C. Arroliga Chairman and Professor Dr. A. Ford Wolf and Brooksie Nell Boyd Wolf Centennial...

Alejandro C. ArroligaChairman and Professor

Dr. A. Ford Wolf and Brooksie Nell Boyd WolfCentennial Chair of Medicine

DVT/PE Prophylaxis

No conflict of interest to report

• Epidemiology

• Diagnosis

• Treatment (very brief review)

• Prophylaxis• Pharmacologic• Mechanical• IVC filters

Epidemiology

• Symptomatic VTE occur in 1-2 per 1000 adults each year (8-fold higher in patients 80 y/o or older compared with 50 y/o)

• The case fatality rate for PE, exceeds the mortality rate for acute myocardial infarction

• It is estimated that 50,000 to 100,000 die of VTE annually in the USA, 10% of patients with symptomatic VTE die within one hour of onset

• mortality risk with systolic hypotension, CHF, cancer, tachypnea, right ventricular hypokinesis , COPD, and age older > 70 years .The mortality rate at one year is ≈ 25%.

Horlander KT, et al. Arch Intern Med 2003;163:1711-1717Lapner ST and Kearon C. BMJ 2013; 346:f757.doi10.1136:Tagalakis V, et al. Am J Med 2013; 126: 832

White R. Circulation 2003;107:I4-I8Heit JA. Clin Chest Med 2003;24:1-12Greer IA. Clin Chest Med 2003;24:123-137Price DT, Ridker PM. Ann Intern Med 1997;127:895-903Tagalakis V, et al. Am J Med 2013; 126: 832

• 62% of VTE is associated to a major risk factor• First episode of VTE: 18% of patients have malignancy,

23% underwent surgery within two months, 15% during hospitalization for medical illness, 2% have major trauma, and 41% are idiopathic.

• VTE is also a women’s health issue as pregnancy (five times), hormonal contraception (four-fold), and postmenopausal therapy (2-4-fold) each contribute to risk

PIOPED II• Diagnostic yield of Multidetector CT with Angiography +/-

venography• 824 patients (90% ambulatory)

Methods• Prospective cohort 2001 to 2003

• Wells’ instrument to classify pre test probability• V/Q, US, if needed pulmonary angiography• Follow up at 3 and 6 months for those with negative

work-up• PE diagnosed with: V/Q High Probability with no history

of PE, angiography, or USG + with an abnormal VQ.

Stein NEJM 2006

PIOPED II

Positive predictive value is the probability that subjects with a positive screening test truly have the disease.Negative predictive value is the probability that subjects with a negative screening test truly don't have the disease.

PIOPED II

• Patients with a moderate to high suspicion for PE, CT has a strong predictive value if is concordant with the clinical suspicion

• Although venography increase the sensibility of CT, the increase does not justify the radiation

• 55% had DVT: 85% in the thigh, 3% in pelvis and 12% in both

• 17 % had false negative or positive en the CT angio• 23% could not undergo the CTA

• To evaluate the diagnostic yield of an algorithm for the diagnosis of VTE

• 12 community and referral hospitals in Holland• 3306 in and outpatients (82%)• Prospective cohort from 2002 to 2004

• Modified Wells• CT angio (simple or MDCT) in the first 24 hr• Follow up at 3 months• The primary outcome was the incidence of

symptomatic VTE during 3 months

JAMA 2006

CHRISTOPHER study

CHRISTOPHER study

5.3%

66.7%

12.1% PE

32.3%

CHRISTOPHER study

Christopher Study

• The risk of VTE for those patients in whom the CT excluded VTE is consistent:

• 3-month incidence:• CHRISTOPHER Study 1.3%• PIOPED 1.7%• Hull (ann Intern Med 1994) 1.9%• Perrier (Ann Intern Med 2001) 0.9%• Wells (Ann Int Med 2001) 0.6 %• Musset (Lancet 2002) 1.8% Inpatient 4.78% (1.8 –

10.1%)

• Assessment of pretest probability is an essential step before ordering a CT angio and when PE is unlikely, a negative highly sensitive D-dimer test result allows anticoagulation withhold without a CT

• >50% of CT angio are not concordant with recommendations

Adams DM, et al. Am J Med 2013; 126: 36-42

The embolism rate was 9.7%

Current and evolving anticoagulation regimens for acute pulmonary embolism..

Konstantinides S , and Goldhaber S Z Eur Heart J 2012;33:3014-3022

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012. For permissions please email: [email protected]

72,000 patients Unstable with PE

Stein PD and Matta F. Am J Med 2013; 126: 304

Stein PD and Matta F. Am J Med 2013; 126: 304

72,000 patients Unstable with PE

NNT 2 to 8

Alteplase en TEP Submasiva

Konstantinides S, et al. N Engl J Med 2002;347:1143-1150

Diseno Prospectivo, randomized, ciego, placebo-control

Inclusion 1) TEP confirmada2) Con cualquiera de los siguiente:

a) Disfuncion VD (sin disfuncion VI) en ecob) Hypertension pulmonary en eco or swanc) Stress del VD en ECG

Exclusion 1) Edad >80 anos2) Sistolica <90 mm Hg3) >96 hrs desde el diagnostico4) Contraindicacion al trombolitico

Intervencion Alteplase 10 mg IV bolo, seguido 90 mg IV en 2 hrs + HNF vs. placebo + HNF

Resultado primario Mortalidad intrahospitalaria o deterioro clinico que requirio escalar el tratamiento

Courtesy of Eduardo Mireles, M.D.

Alteplase en TEP submasiva

Konstantinides S, et al. N Engl J Med 2002;347:1143-1150

Alteplase + HNF(n = 118)

HNF(n = 138) P

Mortalidad intrahospitalaria o escalada terapeutica

13 (11.0) 34 (24.6) 0.006

Mortalidad total 4 (3.4) 3 (2.2) 0.71

Escalada terapeutica 12 (10.2) 34 (24.6) 0.004

Incremento catecolaminas 3 (2.5) 8 (5.8) 0.33

Trombolisis secundaria 9 (7.6) 32 (23.2) 0.001

Intubacion 3 (2.5) 3 (2.2) 0.85

RCP 0 1 (0.7) 1

Embolectomia o cateter 0 1 (0.7) 1

Hemorragia mayor 1 (0.8) 5 (3.6) 0.29

Data presented as n (%); CPR = cardiopulmonary resuscitation

PIETHO

Diseno Prospectivo, randomizado, ciego, placebo-control

Inclusion 1) TEP confirmada2) Con:

a) Disfuncion VD por TAC o Ecob) Elevacion troponina

Exclusion 1)Filtro VC, trombolisis o embolectomia reciente

2)SBP <90 mm Hg3)Riesgo de sangrado4)Contraindicacion a thrombolisis

Intervencion Tenecteplase basado en peso IV bolus + HNF vs. placebo + HNF

Resultado primario Mortalidad o colapso hemodinamico en primeros 7 dias

PEITHO PIETHO

Courtesy of Eduardo Mireles, M.D.

PIETHO

Does Prophylaxis Really Work?

• The rate of DVT and PE is reduced by chemical prophylaxis by 55% to 63% with the use of an heparin.

• Prophylaxis is underutilized, in the DVT-Free Registry 5451 patients with confirmed DVT were enrolled, of the 2726 who had their DVT diagnosed while in the hospital, only 42% received prophylaxis within 30 days before diagnosis.

• In the CURVE study (Canadian survey study),1894 patients were enrolled from 28 hospital. Prophylaxis were given to 23% of all patients and in 37% of bedridden patients. Only 16% received appropriate prophylaxis.

• In the IMPROVE study (15,156 patients at high-risk), 60% received appropriate VTE prophylaxis.

Annals Thoracic Med 2010; 5: 195

Does Prophylaxis Really Work?

• A higher proportion of surgical patients received prophylaxis:• 93% of patients that underwent high-risk

orthopedic surgery• 75% who underwent high-risk major abdominal

surgery

Chest 2011; 139: 1317

Do We Give Prophylaxis?

• Using a database of 15,721 patients admissions from 1/2005 to 11/2007 in a Premier Perspective database, only 39% of patients received prophylaxis {highest rate in patients with cancer (52%)}

• The cost of treatment in 26 hospital units in Italy was four times higher than those for prophylaxis (1,348 vs. 373 Euros) and prophylaxis accounted for 4.5% of the total cost in patients with no VTE

Clin Appl Thromb Hemost 2011 Gussoni G, et al Thromb Res 2013; 131: 17

Among 55 studies, there was a statistically significant improvements in rates of prescription of prophylaxis an appropriate prophylaxis associated with alerts, education and multifaceted intervention strategies

Khan SR, et al. Cochrane Database Syst Rev 2013 Jul 7Piazza G, et al. Am J Med 2013; 126: 435

Khan SR, et al. Cochrane Database Syst Rev 2013 Jul 7

40 Unique RCT and 52,000 Patients

2011; 155: 602

Non Surgical patients: Heparin vs. No heparin


2011; 155: 602

Non Surgical patients: LMWH vs UFH


2011; 155: 602

Recommendations Level of Evidence Guideline

Assessment of risk of VTE and bleeding before prophylaxis

Strong recommendation, moderate quality

ACP

Pharmacological prophylaxis with heparin or related drug for medical patients (including stroke) unless risk of bleeding is high


ACP

Use of compression stocking not recommended


ACP

Acutely ill, medical patients at low risk, no use of pharmacological or mechanical prophylaxis


ACCP

Acutely ill, medical patients at high risk, use LMWH, LDUH twice or three times daily, or fondaparinux


ACCP

Prophylaxis for Medical Patients

Hospital Practice 2013; 41: 60

Prophylaxis for Medical PatientsRecommendations Level of Evidence Guideline

Acutely ill medical patients who receive prophylaxis, no extension of prophylaxis beyond immobilization or acute stay

Weak recommendation, moderate quality

ACCP

Acutely ill medical patients at risk of VTE, bleeding or at high risk of bleeding, mechanical prophylaxis with GCS or IPC rather than no prophylaxix


ACCP

When bleeding risk decrease, persistent VTE risk, substitute to pharmacological prophylaxis


ACCP

For critically ill use LMWH or LDUH Weak recommendation, low quality

ACCP

For critically ill if bleeding or at high risk use mechanical prophylaxis

Weak recommendation, low quality

ACCP

Hospital Practice 2013; 41: 60

Prophylaxis in Cancer Patients

Recommendations Level of Evidence Guideline

Use of LMWH once a day (at the highest dose) or UFH three times a day for post op for 7-10 d

Grade 1A. Strong recommendation. Unlikely to change

International Guideline

No evidence to support for fondaparinux Grade 2C. No confident, further research is needed

For medical patients use LMWH, UFH or fondaparinux in hospitalized patients

Grade 1B. Strong recommendation. Further research may change estimate

In patients receiving chemo, no prophylaxis, except in metastatic disease?

Grade 1B

Recommend use of LMWH or UFH post op in patients undergoing neurosurgery.LMWH was superior to ECD

Grade 1A

Farge D, et al. J Thromb Haemost 2013; 11: 56

16,000 Patients From 70 Trials

Ho KM and Tan JA. Circulation 2013; 128: 1003

• The risk of bleeding complications is decrease compared with pharmacologic prophylaxis

• IPC is as effective as pharmacologic prophylaxis in reducing PE and DVT

• Adding IPC to pharmacologic measures reduce risk of DVT but not of PE and mortality was similar

Ho KM and Tan JA. Circulation 2013; 128: 1003

Conclusions

• VTE is very common

• The diagnosis strategy should include risk stratification, imaging studies, echo and BNP, troponin in submassive PE

• Prophylaxis is cheaper and cost effective. It could be increase with comprehensive planning that include reminders and education

• Pharmacological prophylaxis reduce the incidence of PE and DVT but does not modify mortality

• Mechanical prophylaxis such as IPC reduce incidence of PE and DVT

• IVC filters are being overused

Increasing Use of Vena Cava Filters For Prevention Of Pulmonary Embolism

• Indications for insertion of IVC filters are:• contraindication to anticoagulants• recurrence of PE despite adequate therapy• PE severe enough that a new one may be fatal

• Other indications (more opinion than fact) include:• Following embolectomy• A free-floating thrombus in the IVC• Prophylaxis in patients with cancer, trauma, burns, acetabular fracture,

hip or knee replacement in patients with history of VTE

• In some studies*, the use of IVC filter was considered appropriate in only 51% of patients

Am J Med 2011; 124: 655*Arch Intern Med 2010; 170: 1456


•From 1979 to 1984, 17,000 filters were inserted.•In 2006 only, 92,000 filters were inserted in hospitalized patients•Of the retrievable filters only 8.5% were removed

Am J Med 2011; 124: 655JAMA Intern Med 2013; 173: 513


•The proportion of patients with PE with or without DVT and DVT alone who receive a filter increased linearly•The proportion of patients without DVT or PE who received a filter increased 3-fold from 2001 onward•Only 3.2% (31 of 978) sustained a VTE and were anticoagulants failures

Am J Med 2011; 124: 655JAMA Intern Med 2013; 173: 513

Conclusions

• VTE is very common

• The diagnosis strategy should include risk stratification, imaging studies, echo and BNP, troponin in submassive PE

• Prophylaxis is cheaper and cost effective. It could be increase with comprehensive planning that include reminders and education

• Pharmacological prophylaxis reduce the incidence of PE and DVT but does not modify mortality

• Mechanical prophylaxis such as IPC reduce incidence of PE and DVT

• IVC filters are being overused

Alejandro C. Arroliga Chairman and Professor Dr. A. Ford Wolf and Brooksie Nell Boyd Wolf Centennial...

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