Identikit del paziente ricoverato da sottoporre a profilassi del TEV

Il punto di vista dell’Internista

C. Cimminiello – Vimercate (MB)

Oncologo e Internista insieme nella gestione del paziente neoplastico a rischio di TEV

Roma 13-14 giugno 2012

Relazioni con soggetti portatori di interessi commerciali in campo sanitario

• Ai sensi dell’art. 3.3 sul Conflitto di Interessi, pag. 17 del Regolamento Applicativo dell’Accordo Stato-Regione del 5 novembre 2009, dichiaro che negli ultimi due anni ho avuto i seguenti rapporti anche di finanziamento con soggetti portatori di interessi commerciali in campo sanitario:

– Bayer

– Boehringer Ingelheim

– sanofi aventis

Il paziente oncologico ricoverato in Medicina Interna

• Diagnosi di malattia non nota: segni e sintomi acuti e sottostante neoplasia ancora indiagnosticata

• Malattia nota: progressione della stessa/ patologia concomitante

• Malattia nota: complicanze del trattamento (es. neutropenia febbrile)

*Only includes patients age 65 years

Frequency of Venous Thrombosis in Hospitalized Patients With Cancer

Study No. of Hospitalization or Patients

Events No. %

Levitan et al* 1,211,944 7,238 0.6

Sallah et al 1,041 81 7.8

Khorana et al 66,106 5,272 5.4

Khorana et al 1,015,598 41,666 4.1

Francis CW JCO 2009

MEDENOX 1,102 1%

Incidence of Venous Thromboembolism in Patients Hospitalized with Cancer

Patients discharged from 1979 through 1999 with diagnosis of DVT/PE (National Hospital Discharge Survey).

Stein PD et al Am J Med 2006; 119: 60-68

Pts without malignancy 66,2309,000 with VTE 6,854,000 1.0% Pts with malignancy 40,787,000 with VTE 837,000 2.0%

Incidence of Venous Thromboembolism in Patients Hospitalized with Cancer

Patients discharged from 1979 through 1999 with diagnosis of DVT/PE (National Hospital Discharge Survey).

Stein PD et al Am J Med 2006; 119: 60-68

Pts without malignancy 66,2309,000 with VTE 6,854,000 1.0% Pts with malignancy 40,787,000 with VTE 837,000 2.0%

Acute Medical Illness and VTE

Multivariate Logistic Regression Model for Definite Venous Thromboembolism (VTE)

Alikhan R, Cohen A, et al. Arch Intern Med. 2004;164:963-968

Risk Factor Odds Ratio (95% CI)

X2

Age > 75 years Cancer

Previous VTE

1.03 (1.00-1.06) 1.62 (0.93-2.75) 2.06 (1.10-3.69)

0.0001 0.08 0.02

Acute infectious disease 1.74 (1.12-2.75) 0.02

Venous thromboembolism risk stratification in medically-ill hospitalized cancer patients. A comprehensive cancer center experience

606 cancer pts admitted to regular medical units between August and December 2008 and followed-up to 2 months after discharge

Abdel Razeq H et al J Thromb Thrombolysis 2010;30:286-293

Venous thromboembolism risk stratification in medically-ill hospitalized cancer patients. A comprehensive cancer center experience

606 cancer pts admitted to regular medical units between August and December 2008 and followed-up to 2 months after discharge

Abdel Razeq H et al J Thromb Thrombolysis 2010;30:286-293

Venous thromboembolism risk stratification in medically-ill hospitalized cancer patients. A comprehensive cancer center experience

606 cancer pts admitted to regular medical units between August and December 2008 and followed-up to 2 months after discharge

Abdel Razeq H et al J Thromb Thrombolysis 2010;30:286-293

Venous thromboembolism risk stratification in medically-ill hospitalized cancer patients.

A comprehensive cancer center experience

606 cancer pts admitted to regular medical units between August and December 2008 and folloed-up to 2 months after discharge

Abdel Razeq H et al J Thromb Thrombolysis 2010;30:286-293

6

5

4

3

2

1

3.38%

4.2%

0

Low risk Moderate risk High risk

2-m

on

th V

TE in

cid

ence

Low risk group: prophylaxis in 25.9% Moderate risk group: prophylaxis in 53.3% High risk group: prophylaxis in 62.2%

Cancer-associated acute venous thromboembolism Findings from the MASTER Registry

Imberti D et al Haematologica 2008; 93:273-278

With cancer N: 424

Without cancer N: 1695

V

TE in

cid

ence

in p

atie

nts

wit

h

seve

re m

edic

al d

isea

se 12.7%

7.1%

P < .001

12

10

8

6

4

2

14

Thromboembolism in Hospitalized Neutropenic Cancer Patients

Retrospective cohort study (discharge database of the University Health System Consortium) including 66,106 adult neutropenic cancer patients with 88,074 hospitalizations between 1995 and 2002 at 115 medical centers in the United States

Predictors of Venous Thromboembolism by Multivariate Logistic Regression Analysis

Khorana AA et al J Clin Oncol 2006; 24:484-490

Thromboembolism in Hospitalized Neutropenic Cancer Patients

Retrospective cohort study (discharge database of the University Health System Consortium) including 66,106 adult neutropenic cancer patients with 88,074 hospitalizations between 1995 and 2002 at 115 medical centers in the United States

Thromboembolism and inpatient mortality

Khorana AA et al J Clin Oncol 2006; 24:484-490

Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada

The CURVE Study Aim: to determine the frequency, determinants and appropriateness of thromboprophylaxis in 1894 medical pts in

29 Canadian hospitals

Kahn S et al Thromb Res2007;119:145-155

Predictors of use of any prophylaxis in study population

Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada

The CURVE Study Aim: to determine the frequency, determinants and appropriateness of thromboprophylaxis in 1894 medical pts in

29 Canadian hospitals

Kahn S et al Thromb Res2007;119:145-155

Predictors of use of mechanical prophylaxis in study population

Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWIss

Venous ThromboEmbolism Registry (SWIVTER)

257 cancer patients (61 ± 15 years) with acute VTE and prior hospitalization for acute medical illness or surgery within 30 days

Kucher N et al Ann Oncol 2010; 21: 931–935

Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWIss

Venous ThromboEmbolism Registry (SWIVTER)

Kucher N et al Ann Oncol 2010; 21: 931–935

Independent clinical predictors of prophylaxis in patients with cancer

In-hospital symptomatic venous thromboembolism and antithrombotic prophylaxis in Internal Medicine

Findings from GEMINI Study Multivariable regression analysis to correlate known risk factors for VTE and prescription of

antithrombotic prophylaxis during hospital stay.

Gussoni G et al Thromb Haemost 2009; 101: 893–901

Percentage of antithrombotic prophylaxis administration in cancer patients, according to the number of additional known risk factors for VTE

In-hospital symptomatic venous thromboembolism and antithrombotic prophylaxis in Internal Medicine

Findings from GEMINI Study

Gussoni G et al Thromb Haemost 2009; 101: 893–901

Prophylaxis rate in a cancer population with VTE according to number of risk factors

Abdel-Razeq H et al J Thromb Thrombolysis 2011 ;31:107-12

Prophylaxis rate in a cancer population with VTE in relation to recent hospitalization

Abdel-Razeq H et al J Thromb Thrombolysis 2011 ;31:107-12

Trials of Anticoagulant Prophylaxis for Venous Thromboembolism in Hospitalized Medical Patients

Study Total No. of Patients

Patients With Cancer

No. %

Relative Risk

Placebo Events

No./Total No. % No./Total No. %

ARTEMIS 849† 131 15.4 34/323 10.5 18/321 5.6 0.47 0.08 to 0.69 .029

MEDENOX 579 72 12.4 43/288 14.9 16/291 5.5 0.37 0.22 to 0.63 .001

PREVENT 3,706 190 5.1 73/1,473 4.96 42/1,518 2.77 0.55 0.38 to 0.8 .0015

Treatment Events

95% CI

P

Francis CW JCO 2009

Cosa dicono le CONSENSUS e le Lineeguida

1. Hospitalized patients with malignancies and concomitant acute medical illness should receive prophylactic doses of LMWH or fondaparinux (grade A)

2.3. For acutely ill hospitalized medical patients at increased risk of thrombosis, we recommend anticoagulant thromboprophylaxis with lowmolecular- weight heparin [LMWH], low-dose unfractionated heparin (LDUH) bid, LDUH tid, or fondaparinux (Grade 1B)

S. Siragusa et al. Thrombosis Research 2012; 129: e171–e176

Kahn S et al. CHEST 2012; 141(2)(Suppl):e195S–e226S

“No studies are available in which prophylaxis has been evaluated in a population limited to patients with cancer….. However, patients with cancer have an increased risk for bleeding, resulting from factors such as thrombocytopenia and the performance of invasive procedures that occurs more commonly than in other medical patients. Thus, care should be exercised in administering anticoagulant prophylaxis…”

Francis CW JCO 2009

EXCLAIM Symptomatic VTE Bleeding

MAGELLAN Bleeding

ADOPT VTE Bleeding

VTE

Extended Prophylaxis: the “Big Three”

Età >75 anni o Storia pregressa di TEV

o Diagnosi di neoplasia

+ Mobilità Livello 1

(pazienti totalmente allettati o sedentari)

Mobilità Livello 2

(livello 1 con possibilità di raggiungere il bagno)

oppure

Studio EXCLAIM: selezione dei pazienti Età ≥40 anni Allettamento (≤3 giorni) Patologia medica acuta

scompenso cardiaco, classe NYHA III/IV

insufficienza respiratoria acuta

altre condizioni mediche acute, inclusi:

ictus ischemico post-acuto

infezione acuta in assenza di shock settico

neoplasia in fase attiva

Hull RD et al. J Thromb Thrombolysis 2006;22:31-38

Hull RD et al. J Thromb Thrombolysis 2006;22:31-38

Profilassi prolungata: per quali pazienti?

CONCLUSIONI

• Il paziente neoplastico ricoverato è ad elevato rischio di TEV se coesistono altri fattori di rischio.

• La profilassi del TEV viene sottoutilizzata in questi pazienti.

• Non esistono dati specifici, raccolti in casistiche di soli pazienti neoplastici, sull’efficacia e sulla SICUREZZA della profilassi farmacologica del TEV.

• La profilassi protratta – sul modello EXCLAIM – potrebbe essere considerata in alcune tipologie di pazienti neoplastici ricoverati (es. oltre i 75 anni e con ipomobilità perdurante)