1

CURRENT STATUS AND INDICATIONS FOR

INTERMITTENT PNEUMATIC COMPRESSION

A N Nicolaides

Emeritus Professor of Vascular Surgery, Imperial

College, London.

Hon. Professor of Surgery, University of Nicosia

Medical School, Cyprus

2

Disclosures

Honoraria for lectures received from:

Covidien / Medronic

Alpha Wasserman / AlphaSigma

Servier

Pierre Fabre

3

HISTORY

Intermittent Pneumatic Compression (IPC)

was developed in the late 1970s to prevent DVT

Sequential compression device (SCD) with multiple

chambers was shown to be more effective than single

chamber devices in preventing perioperative DVT

Nicolaides et al, Brit J Surg 1978;65:359-363

Nicolaides et al, Surgery 1983;94:21-26

4

Developed under the auspices of the:

Cardiovascular Disease Educational and Research Trust (UK)

European Venous Forum

North American Thrombosis Forum

International Union of Angiology and

Union Internationale du Phlebologie

PREVENTION AND TREATMENT

OF VENOUS THROMBOEMBOLISM

International Consensus Statement 2013Guidelines According to Scientific Evidence

5

EDITORIAL COMMITTEE

Chairman: AN Nicolaides,

Cochairmen: J Fareed, AK Kakkar

Members: AJ Comerota, SZ Goldhaber, R Hull, K Myers,

M Samama, J Fletcher

Editorial Secretary: E Kalodiki

6

Faculty

D Bergqvist (Sweden)

J Bonnar (Ireland)

JA Caprini (USA)

C Carter (USA)

AJ Comerota (USA)

J Conard (France)

B Eklof (Sweden)

I Elalamy (France)

J Fareed (USA)

J Fletcher (Australia)

G Gerotziafas (France)

G Geroulakos (UK)

A Giannoukas (Greece)

SZ Goldhaber (USA)

I Greer (UK)

M Griffin (UK)

R Hull (USA)

A K Kakkar (UK)

S Kakkos (Greece)

E Kalodiki (UK)

MR Lassen (Denmark)

GDO Lowe (UK)

A Markel (Israel)

K Myers (Australia)

A Nicolaides (Cyprus)

P Prandoni (Italy)

G Raskob (USA)

M Samama (France)

AC Spyropoulos (USA)

AG Turpie (Canada)

JM Walenga (USA)

D Warwick (UK)

7

8

Corresponding Faculty

C Allegra (Italy)

J Arcelus (Spain)

N Baekgaard (Denmark)

G Belcaro (Italy)

H Bjarnason (USA)

MA Cairols (Spain)

M Catalano (Italy)

D Christopoulos (Greece)

D Clement (Belgium)

F Corvalán (Chile)

E Diamantopoulos (Greece)

J Fernandes e Fernandes

(Portugal)

C Fisher (Australia)

A Gasparis (USA)

H Gibbs (Australia)

V Hadjianastassiou (Cyprus)

K Ivancev (UK)

CP Hsien (Thaiwan)

JT Hobbs (UK)

D Hoppenstead (USA)

EA Hussein (Egypt)

O Iqbal (USA)

K Ivancev (Russia)

R Kistner (USA)

TK Kim (Korea)

M Kurtoglou (Turkey)

T Kölbel (Germany)

N Labropoulos (USA)

LH Lee (Singapore)

BB Lee (USA)

Y-J Li (China)

NC Liew (Malaysia)

A Llinas (Colombia)

M Nakamura (Japan)

P Neglen (Cyprus)

L Norgren (Sweden)

H Partsch (Austria)

N Ramakrishnan (India)

G Rao (USA)

J-B. Ricco (France)

N Rich (USA)

P Robless (Singapore)

W Schobersberger (Austria)

M Seed (UK)

S Schellong (Germany)

A Scuderi (Brazil)

R Sexana (India)

E Shaydakov (Russia)

A Shevela (Russia)

R Simkin (Argentina)

W Toff (UK)

JM Trabal (Puerto Rico)

M Vandendriessche

(Belgium)

M Veller (South Africa)

L Villavincencio (USA)

R Wahi (USA)

C Wittens (TheNetherlands)

R Wong (Hong Kong)

9

Outcomes

Evidence is presented for the following outcomes

asymptomatic DVT at screening

symptomatic DVT or PE,

fatal PE,

overall mortality and

development of the post-thrombotic syndrome (PTS) when

available

The decision to use asymptomatic DVT as well as

symptomatic DVT or PE is a subjective one based on

the following arguments

10

Arguments

The relationship between asymptomatic and symptomatic VTE

including PE has been known for some time.1-3

Reduction in the incidence of asymptomatic DVT has been shown

to be associated with a reduction of symptomatic DVT and PE4-6

Large studies that were powered to study efficacy on fatal PE have

demonstrated that reduction in silent DVT is accompanied by

reduction in clinical DVT, clinical PE and fatal PE.7

1. Kakkar VV.Ann R Coll Surg Engl. Nov 1969;45:257-276.

2. Philbrick JT et al Arch Intern Med. Oct 1988;148(10):2131-2138.

3. Hull RD et al Ann Intern Med. Jun 1983;98(6):891-899.

4. Giannoukas AD et al Eur J Vasc Endovasc Surg. Nov 1995;10(4):398-404.

5. Hull RD et al Ann Intern Med. Nov 20 2001;135(10):858-869.

6. Eikelboom JW et al Lancet 2001;358:9-15.

7. Kakkar VV et al Lancet. July 12 1975;306(7924):45-51.

11

Arguments

Regulatory authorities have recognized asymptomatic proximal

DVT as a valid endpoint of clinical trials and drug evaluation

Relatively few PE occur in patients with symptomatic DVT

The majority of PE including fatal PE occur in patients with

asymptomatic DVT

Thus, asymptomatic DVT is an important stage of thromboembolic

disease that has not yet manifested itself.

12

Effect of IPC in General Surgery (11 studies)

0

5

10

15

20

25

30

DVT (%)

Control (n = 658) IPC (n=660)

68% Reduction

in DVT

Incidence

p < 0.001

13

General Considerations of TherapyIntermittent Pneumatic Compression

Effect of IPC in prevention of DVT diagnosed by objective methods (FUT or phlebography) in non-orthopaedic surgical RCTs1-10

1. Sabri S, et al. Br Med J. 1971; 4:394-6.

2. Hills NH, et al. Br Med J. 1972; 1:131-5.

3. Roberts VC, et al. Br Med J. 1974; 1:358-60.

4. Clark WB, et al. Lancet. 1974; 2:5-7.

5. Turpie AG, et al. Neurology. 1977; 27:435-8.

6. Coe NP, et al. Surgery. 1978; 83:230-4.

7. Skillman JJ, et al. Surgery. 1978; 83:354-8.

8. Turpie AG, et al. Thromb Res. 1979; 15:611-6.

9. Butson AR. Am J Surg. 1981; 142:525-7.

10. Clarke-Pearson DL, et al. Obstet Gynecol. 1984; 63:92-8.

14

IPC vs Heparin Prophylaxis (DVT)Eppsteiner RW et al World J Surg 2010;34:10-19

Favours IPC Favours Heparin

15

IPC vs Heparin Prophylaxis (Bleeding)Eppsteiner RW et al World J Surg 2010;34:10-19

Favours IPC Favours Heparin

16

IPC in Orthopedic Surgery

IPC in Elective Hip Surgery

IPC In Elective Knee Replacement

17

Effect of Foot Impulse Technology with GEC on Proximal DVT

Hip and knee replacement (7 studies):

Proximal DVT was reduced from 26% to 10%

RR 0.39 (95% CI 0.28 to 0.54)

18

Combined Modalities

19

IPC + Heparin vs IPC or Anticoagulant (DVT) (14 Studies)

Combined IPC or Anticoag.

TOTAL 63/3074 200/3238

2.05% 6.18% p < 0.001

OR 0.31 (95% CI 0.23 to 0.43) or 69% reduction

Kakkos S et al Cochrane Database Syst Rev 2008:CD005258

20

IPC + Heparin vs IPC or Anticoagulant (Symptomatic PE) ( 16 Studies)

Combined IPC or Anticoag.

TOTAL 33/3838 122/4313

0.86% 2.83% p < 0.001

OR 0.34 (95% CI 0.23 to 0.50) or 67% reduction

Kakkos S et al Cochrane Database Syst Rev 2008:CD005258

21

Effect of Combined Modalities and PE(LD Heparin + SCD vs LD Heparin)

▪ Cardiac surgery (2482 randomised patients)

PE was reduced from 4% to 1.5%

RR 0.37 (95% CI 0.22 to 0.63)

Ramos et al Chest 1996

▪ Oesophagectomy (997 patients)

PE was reduced from 3.2% to 0.7%

RR 0.23 (95% CI 0.05 to 0.93)

Tsutsumi et al Surg Today 2000

22

APOLLO

A Multicenter, Randomized, Double-Blind,

Placebo-Controlled Study of patients having

abdominal surgery

ARIXTRA + IPC (n=650)

vs IPC used alone (n=659)

Turpie AG, Bauer KA, Caprini JA et al. J Thromb Haemost. 2007 Sep;5(9):1854-61

23

Conclusions

Clinal Results: 1 DVT and 1 non-fatal PE in each group

IPC + Fondaparinux reduced venographic rate by 70%

compared with IPC alone (1.7% vs. 5.3%).

IPC + Fondaparinux reduced proximal DVT from 1.7%

to 0.2% ( P = 0.037) compared with IPC alone.

Major bleeds occurred in 1.6% and 0.2% of

Fondaparinux-treated and placebo-treated patients,

respectively (P = 0.006), none being fatal or involving a

critical organ.

24

IPC and IPC+LMWH cost-effectiveness

Conclusion: IPC and IPC+LMWH are cost-effective versus LMWH after

lower-limb arthroplasty in the USA and Australia. The choice between

IPC and IPC+LMWH depends on expected bleeding risks.

R Saunders et al. ClinicoEconomics Research 2018;10:231-241

25

Conclusion

Compared to single modalities, combined

prophylactic modalities significantly decrease the

incidence of both postoperative DVT and PE in a

variety of specialties, including orthopedic, general

and cardiac surgery.

The results support their use, especially in high risk

patients (e.g. thrombophilia or previous VTE)

26

CLOTS 3 Study:

Patients with acute stroke

• Multicenter, RCT, parallel group

• Patients enrolled from Day 0 to 3 of hospital admission

• Randomized to receive either IPC or no IPC

• Duplex scanning on both legs by a blinded technician

at Day 7-10 and Day 25-30

• 6 months follo-up to determine survival and later

symptomatic VTE

27

CLOTS 3 (n=2876)Results – Primary Outcome

December 2008 to

September 2012

105 Centres

in the UK

28

CLOTS 3Secondary Outcomes

29

Acute Stroke- Historical

Control vs LDUH 50% reduction in DVT (10 studies)

66% reduction in PE

LDUH vs LMWH 41% further reduction in DVT (2 studies)

Problem: Major intracranial hemorrhage increased from 1.1% to 2.6%

GEC vs GEC+IPC* 71% reduction in DVT (15.9% to 4.7%)

Control vs IPC** CLOTS3 study

25% reduction in all DVT (30 days)

35% reduction in proximal DVT (30 days)

14% reduction in mortality (6 months)

* Hemorrhagic stroke , ** Ischemic stroke

30

Recommendations - General Surgery

Moderate risk patients (major general surgery,

age >40, no additional risk factors)

(LDUH) or LMWH LE: high

IPC + GEC LE: high

31

Recommendations – General Surgery

High risk patients (major general surgery, age

> 60 or age > 40 with at least one additional

risk factor)

(LDUH) LMWH LE: high

IPC + GEC LE: high

Fondaparinux (one study) LE: moderate

Combined modalities LE: high

32

Efficacy in Elective Hip Replacement(Historical progression)

Control vs LDUH 50% reduction in DVT (20 sudies)

Control vs IPC 52% reduction in DVT (4 studies)

LDUH vs LMWH 54% further red. in DVT (10 studies)

LMWH vs Fondaparinux 24% further red. In DVT (2 studies)

50% further red. In PE (2 studies)

LMWH vs LMWH+IPC 28% vs 0% DVT (1 study)

33

Recommendationsfor Elective Hip Replacement (2013)

Fondaparinux LE: high (Most effective)

LMWH LE: high

IPC + GEC LE: high (Equivalent to LMWH)

IPC+GEC+LMWH LE: high (More effective than either)

Rivaroxaban, Dabigatran LE: high

34

Effect of IPC in PTS

1. Lowers venous pressure in the sitting position

2. Reduces edema

3. Increases fibrinolytic activity

4. Increases TFPI

5. Increases TcPO2

6. Increases oxygen diffusion barrier

7. Increases capillary perfusion

8. Increases skin nutrition

Comerota AJ J Vasc Surg 2011;53:1121-9

35

Effect of IPC on Healing of Venous Ulcers

RCT Duration IPC+GEC GEC

Hazarika &

Wright 1981 10 m 8/9 1/12

McCulloch 1994 6 m 12/12 8/10

Smith et al, 1990 3 m 10/21 1/23

Shuler et al, 1996 6 m 20/28 12/25

Total 50/70 (71%) 21/70 (30%)

P= 0.005

36

CONCLUSIONS re: IPC

IPC is an effective form of VTE prophylaxis

Use IPC for MODERATE risk patients especially if risk of

haemorrhage is high

Combine IPC with appropriate anticoagulation for high VTE risk

patients

Consider portable IPC devices for out-of-hospital use in very

high risk patients particularly when mobility at home is an issue

Use in combination with elastic compression for healing venous

ulcers