Paziente medico e chirurgico: schemi di trattamento

Walter Ageno

Dipartimento di Medicina Clinica

Università dell’Insubria - Varese

MEDENOX

(enoxaparin)• age ≥ 4040 years,

• hospitalization ≥ 6 6 days

and

• CHF (NYHA III/IV)

• Acute resp. disease

• Infectious disease,acute rheumatic and IBD

• + 1 predefined RF *+ 1 predefined RF *

PREVENT

(dalteparin)• age ≥ 4040 years,

• hospitalization ≥ 6 6 days

and

• CHF (NYHA III/IV)

• Acute resp. disease

• Infectious disease, acute rheumatic and IBD

• + 1 predefined RF *+ 1 predefined RF *

ARTEMIS

(fondaparinux)• age ≥ 600 years,

• hospitalization ≥6 6 days

and

• CHF (NYHA III/IV)

• Acute and chronic resp. disease

• Acute infectious or inflammatory disease

• No additional RFNo additional RF

Main clinical trials in medical patients

age> 75 years, cancer, VTE history, obesity, varicose veins, oral contraceptives, chronic heart failure, chronic respiratory failure

PE RR = 0.43; 95% CI: 0.26-0.71

Fatal PE RR = 0.38; 95% CI: 0.21-0.69

Symptomatic DVT RR = 0.47; 95% CI: 0.22-1.00

Mortality RR = 0.97; 95% CI: 0.79-1.19

Major bleeding RR = 1.32; 95% CI: 0.74-2.37

NINE SELECTED STUDIES → 19,958 PATIENTS

Dentali F et al. Ann Intern Med 2007; 146:278-88.

Thromboprophylaxis in medical patients: meta-analysis on treatment period

Linee guida SPREAD 2010: stroke ischemico

• Grado B: In pazienti a rischio elevato (pazienti plegici, con alterazione dello stato di coscienza, obesi, con pregressa patologia venosa agli arti inferiori) è indicato l’uso di eparina calcica non frazionata 5000 UI x 2 o eparina a basso peso molecolare

• In pazienti non a rischio elevato di trombosi venose profonde, il ricorso sistematico all’eparina comporta un bilancio beneficio/rischio di complicanze emorragiche intracerebrali e/o sistemiche inaccettabile

GCS NO

11.5% 11.7%

Skin breaks/ulcers/blisters/skin necrosis 64 (5.1%) - 16 (1.3%) OR 4.18 (2.40–7.27)

Efficacy of low-dose unfractionated heparin (UFH) in prevention of DVT after major surgery

42

8

0

5

10

15

20

25

30

35

40

45

Control Low-dose UFH

s.c. low-dose UFH pre-operative and b.i.d.post-operative

78 ‘high-risk’ patients

Pat

ient

s w

ith

DV

T (

%)

p < 0.001

Pharmacological preventionof thrombosis in surgical patients

Kakkar VV et al. Lancet 1972;2:101-6.

42

8

LMWH vs. no treatment or placebo (8 studies, 5520 patients)

RR [CI 95%]

0.28 [0.14–0.54]

0.29 [0.11–0.73]

DVT (n=513)

Clinical VTE (n=4890)

Major bleeding (n=5456)

Death (n=5142 )

2.03 [1.37–3.01]

0.54 [0.27–1.10]

LMWH better

10.50 2 3

0.25 [0.08–0.79]Clinical PE (n=5456)

Placebo/No treatment better

Relative risk

LMWH for the prevention of VTE in general surgery

Mismetti P et al. Br J Surg 2001;88:913-30.

Guidelines: Prophylaxis of VTE in surgical patients

1. Geerts WH et al. Chest 20082. Hill J et al BMJ 2007

For higher-risk general surgery patients who

are undergoing a major procedure for cancer,

we recommend thromboprophylaxis with

LMWH, LDUH three times a day, or

Fondaparinux (each Grade 1A)1

For moderate-risk general surgery patients who are

undergoing a major procedure for benign disease, we

recommend thromboprophylaxis with LMWH, LDUH,

or fondaparinux (each Grade 1A).

NICE guidelinesUK

Setting No risk factors Risk factors

General Mechanical Mechanical

surgery + LMWH or

fondaparinux

ENOXACAN II1

Tot

al D

VT

(%

)

1 week 4 weeks

12.0%

4.8%

p=0.02

0

5

10

16.3%

7.3%

FAME 2

p=0.012

*Deep Vein Thrombosis ** Venous Thromboembolism

Incidence of Total DVT* Incidence of VTE**

Enoxaparin: n=165 Dalteparin: n=34360% cancer surgery in 1 week group56% cancer surgery in 4 weeks group

1. Berqvist D et al. New Engl J Med 2002;346:975-80. 2. Rasmussen MS et al. J Thromb Haemost 2006;4:2384-90

Extended prophylaxis with LMWH after cancer surgery

0

2

4

6

8

10

12

14

16

18

1 week 4 weeksV

TE

(%

)

Recommendations: Elective Hip and Knee Replacement

We recommend the routine use of one of the following options:

(1) LMWH (at a usual high-risk dose); (2) Fondaparinux (2.5 mg); (3) Adjusted dose VKA started preoperatively or the eveningof the surgical day (INR target, 2.5; INR range, 2.0 to 3.0) (all Grade 1A)

Geerts et al Chest 2008

EFFICACY

LMWH 12 h preop LMWH 12-48 h post-op

DV

T %

14 Studies - 3545 patients

Timing of the first prophylactic dose of LMWH: results of a meta-analysis

LMWH periop.

19.2%(17-21)

12.4%(10-14)

14.4%(12-17)

Strebel, Arch Int Med, 2002

Geerts et al Chest 2008

Timing of Thromboprophylaxis Initiation

For patients receiving LMWH as thromboprophylaxisin major orthopedic surgery, we recommend starting either preoperatively or postoperatively (Grade 1A).

For patients receiving fondaparinux as thromboprophylaxis in major orthopedic surgery, we recommend starting either 6 to 8 h after surgery or the next day (Grade 1A).

Extended thromboprophylaxis: rationale

JW Eikelboom et al. Lancet 2001

Symptomatic VTE

1.3% 3.3%

HEP C OR

0.38

Geerts et al Chest 2008

Duration of Thromboprophylaxis

For patients undergoing THR, TKR, or HFS, we recommend thromboprophylaxis with one of the recommended options for at least 10 days (Grade 1A).

We recommend that thromboprophylaxis be extended beyond 10 days and up to 35 days after surgery (Grade 1A THR, Grade 2B TKR, Grade 1A HFS). The recommended options for extended thromboprophylaxis in THR includeLMWH, a VKA, or fondaparinux.

Renal Impairment and Anticoagulant Dosing

We recommend that renal function be considered when making decisions about the use and/or the dose of LMWH, fondaparinux, and other antithrombotic drugs that are cleared by the kidneys, particularly in elderly patients, patients with diabetes mellitus, and those at high risk for bleeding (Grade 1A). Depending on the circumstances, we recommend one of the following options in this situation: avoiding the use of an anticoagulant that bioaccumulates in the presence of renal impairment, using a lower dose of the agent, or monitoring the drug level or its anticoagulant effect (Grade 1B).

Geerts et al Chest 2008