Low molecular weight heparin and the treatment of pulmonary embolus l.jpg
This presentation is the property of its rightful owner.
Sponsored Links
1 / 57

Low Molecular Weight Heparin and the Treatment of Pulmonary Embolus PowerPoint PPT Presentation


  • 170 Views
  • Uploaded on
  • Presentation posted in: General

Low Molecular Weight Heparin and the Treatment of Pulmonary Embolus. John Powers November 14, 2000. Cases. 84 wf with known DVT, suspected PE transferred to renal service ? UFH or LMWH in hospital? 38 wm with post-op DVT and PE ? UFH or LMWH? Hospital or Home?

Download Presentation

Low Molecular Weight Heparin and the Treatment of Pulmonary Embolus

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Low molecular weight heparin and the treatment of pulmonary embolus l.jpg

Low Molecular Weight Heparin and the Treatment of Pulmonary Embolus

John Powers

November 14, 2000


Cases l.jpg

Cases

  • 84 wf with known DVT, suspected PE transferred to renal service? UFH or LMWH in hospital?

  • 38 wm with post-op DVT and PE? UFH or LMWH? Hospital or Home?

  • 25 bf with PE and hypoxia (4L NC)? UFH or LMWH? Discharge when?

  • 43 wm s/p craniotomy, now with saddle embolus? UFH or LMWH?


Issue l.jpg

Issue

  • LMW Heparins are well accepted for treatment of DVT

  • LMWH are not well accepted for PE

  • Manifestations of the same disease (venous thromboembolism).


Clinical questions l.jpg

Clinical Questions

1. What is the evidence for the use of LMW Heparin in PE?

2. What is the evidence for home treatment or early discharge in PE patients treated with LMW Heparin?


Outline l.jpg

Outline

  • Introduction

  • LMWH vs UFH in DVT

  • LMWH vs UFH in PE

  • Home treatment/When to discharge

  • Cost

  • Summary


History l.jpg

History

  • 1916 - Heparin discovered

  • 1940s - Standard for VTE

  • 1972 - UFH for DVT prophylaxis

  • 1980s - LMW heparin


Venous thromboembolic disease incidence l.jpg

Venous Thromboembolic Disease - Incidence

  • Venous Thromboembolic Disease affects 1 in 1000

  • 50 % incidence of silent PE in patients with proximal DVT


Venous thromboembolic disease incidence8 l.jpg

Venous Thromboembolic Disease - Incidence

  • PE - 200,000 deaths/year

  • Mortality

    • untreated23 - 87%

    • treated (heparin)8%

  • Recurrent events

    • Oral anticoagulant alone20%

    • Heparin + Oral8%


Mechanism of action l.jpg

Mechanism of Action

  • LMWH is formed through the depolymerization of UFH producing molecules of smaller size

    • Heparin MW - 15,000

    • LMW MW - 5,000


Mechanism of action10 l.jpg

Mechanism of Action

  • Both inhibit thrombin and Factor Xa

  • LMWH preferentially inhibits Factor Xa (less ability to bind thrombin)


Slide11 l.jpg

  • Inhibiting a single molecule of Xa prevents the formation of hundreds of thrombin molecules


Advantages of lmwh l.jpg

Reduced binding to plasma proteins

Reduced binding to macrophages

Reduced binding to platelets

More predictable dose response

Decreased need for laboratory monitoring

Longer half life

Subcutaneous administration

Less thrombocytopenia

Advantages of LMWH


Approved lmwh indications l.jpg

Approved LMWH Indications:

  • DVT Prophylaxis

    • Hip/knee replacement surgery

    • General surgery

  • Treatment of Unstable angina/NQWMI

  • Treatment of DVT with or without PE

    • enoxaparin 1 mg/kg q12 or 1.5 mg/kg q24


Monitoring l.jpg

Monitoring

  • Lab monitoring required with:

    • Weight extremes - >80 or <30 kg

    • Renal insufficiency

  • Monitor Plasma anti-factor Xa levels


Trials l.jpg

Trials

  • Goal:

    • Equivalence between LMW heparin and unfractionated heparin

  • Method:

    • Treatment with UFH or LMWH initially

    • Started on warfarin day 1 to 3

    • Overlapped for 5 days

    • Warfarin for 3 months with followup evaluation


Trials16 l.jpg

Trials

  • Endpoints

    • Recurrent events

    • Major bleed

    • Death

  • Major bleeding

    • Drop in hemoglobin of 2 g/dl

    • Transfusion of 2 units or more

    • Intracranial or retroperitoneal bleed


Lmw heparin and dvt l.jpg

LMW Heparin and DVT

  • American-Canadian Thrombosis Study, NEJM 1992

  • Koopman, et al. NEJM 1996

  • Levine, et al. NEJM 1996

  • Harrison, Archives 1998

  • Dolovich, Archives 2000


American canadian thrombosis study 1992 l.jpg

American-Canadian Thrombosis Study, 1992

  • Objective:

    • Compared Use of UFH vs. LMWH (Logiparin) for in hospital treatment of DVT

  • Exclusion:

    • Active bleeding

    • Previous PE or DVT

    • Thrombocytopenia

    • Severe hepatic or renal failure


Slide19 l.jpg

Results

UFH LMWH

Event 6.9% 2.8%

Bleed 5.0% 0.5%

Death 9.6% 4.7%


American canadian study l.jpg

American-Canadian Study

  • Conclusion:

    • LMWH at least as effective as UFH in hospital for treatment of DVT and could allow for outpatient treatment


Koopman et al l.jpg

Koopman, et al.

  • Evaluated:

    • UFH in hospital vs LMWH at home/early discharge using nadroparin in DVT

  • Exclusion

    • Suspected PE, DVT within 2 years

  • Not Blinded


Slide22 l.jpg

Koopman, et al

UFH LMWH

Event 9.0% 7.0%

PE 2.5% 1.8%

Bleed 2.0% 0.5%

Death 8.0% 6.9%


Koopman et al23 l.jpg

Koopman, et al.

  • LMW heparin group

    • 36% never hospitalized

    • 40% early discharge

    • 25% hospitalized entire time

    • 67% reduction in hospital days

  • Conclusions

    • LMWH can be used to treat low risk DVT at home with similar outcomes to UFH in the hospital


Levine et al l.jpg

Levine, et al.

  • Evaluated:

    • UFH in hospital with enoxaparin at home

  • Exclusion Criteria

    • PE, Two Previous DVTs, Active Bleeding, Coagulation Disorders

  • Sample

    • 50 % of LMW group not hospitalized

    • 50% hosp. for avg 2.2 days

  • Not Blinded


Slide25 l.jpg

Levine Results

UFH LMWH

Event 6.0% 5.0%

Bleed 1.2% 2.0%

Death 6.7% 4.4%

Hospital stay reduced - (6.5 days vs.1.1 days)


Levine l.jpg

Levine

  • Conclusion

    LMW Heparin Is safe and effective for home treatment of proximal DVT


Harrison 1998 l.jpg

Harrison, 1998

  • Evaluated:

    • patient satisfaction with outpatient DVT treatment

  • Results

    • 92% satisfied with training and supportgiven

    • 91% pleased with home treatment

    • 70% felt comfortable self injecting


Dolovich l.jpg

Dolovich

  • Objective:

    • Meta-analysis of 13 trials comparing efficacy and safety of UFH vs LMWH

  • Result:

    • No statistical significance in recurrence, PE, major bleeding, minor bleeding, thrombocytopenia

    • Small difference in overall mortality (RR=0.76) favoring LMWH


Dolovich29 l.jpg

Dolovich

  • Results:

    • No apparent differences in once vs twice daily dosing or in brand of LMWH

    • In patient setting may reduce risk of major bleeding (outpatient setting may need monitoring of patients)


Lmw heparin and pe l.jpg

LMW Heparin and PE

  • Three Randomized, Controlled Trials1. Columbus Investigators 1997, NEJM2. THESEE 1997, NEJM3. American-Canadian Thrombosis 2000, Archives of Int Medicine


Columbus investigators l.jpg

Evaluated:

Exclusion:

1021 randomized to LMWH (reviparin) or UFH. Patients had PE(1/3), DVT, or both

Thrombolytics planned - 12

Contraindication - 68

Anticoag w/in 24 hrs - 200

Difficult followup - 59

Columbus Investigators


Columbus investigators32 l.jpg

Columbus Investigators

UFH LMWH

Event 4.9% 5.3%

Bleed 2.3% 3.1%

Death 7.6% 7.1%


Columbus investigators33 l.jpg

Columbus Investigators

Conclusion:

“LMW Heparin is as effective and safe as UFH for initial management of VTE regardless of PE or previous VTE event.”


Thesee trial l.jpg

THESEE trial

  • Evauated:

    • 612 patients with symptomatic PE randomized to LMWH (tinzaparin) or UFH

    • Diagnosis by angiogram, high prob v/q or intermed prob v/q with + LE dopplers

      Exclusion:

    • Those requiring embolectomy or thrombectomy

    • Active bleeding

    • Contraindication to anticoagulation


Thesee trial35 l.jpg

Evaluated combined endpoint of recurrent event, major bleed, and death

THESEE trial


Thesee trial36 l.jpg

THESEE trial

UFH LMWH

Event 4.5% 3.9%

Bleed 1.9% 1.6%

Death 4.5% 3.9%


Thesee trial37 l.jpg

THESEE trial

Conclusion:

“LMW Heparin is as effective and as safe as UFH in patients with acute PE.”


American canadian thrombosis study l.jpg

American-Canadian Thrombosis Study

  • Evaluated:

    • 200 patients with high probability lung scan randomized to LMW heparin (tinzaparin) or UFH

  • Exclusions:

    • Recent anticoagulation

    • Active bleeding

    • Renal/Hepatic failure


Slide39 l.jpg

American-Canadian Results

UFH LMWH

Event 6.8% 0%

Bleed 1.9% 1.0%

Death 8.7% 6.2%


American canadian thrombosis study40 l.jpg

American-Canadian Thrombosis Study

Conclusion:

“LMWH is no less effective and probably more effective than UFH in the initial treatment of patients with submassive PE.”


Causes of death l.jpg

Causes of Death


Expert opinions l.jpg

Expert Opinions

American College of Chest Physicians Consensus Recommendations (1998):“LMW Heparin can be substituted for unfractionated heparin in the treatment of DVT and stable condition patients with PE.”

  • (Grade AI based on Level I studies)


Expert opinions43 l.jpg

Expert Opinions

  • Cochrane Review (1999)“Since only approximately 25% of patients in this review had a diagnosis of PE, it would be prudent to await further results of new studies prior to adopting LMW heparin as standard therapy.”


What about home wells et al l.jpg

What about home?Wells, et al.

  • Evaluated:

    • expanded eligibility for outpatient treatment administered by home care nurse or patient

  • Results:

    • 194/233 (83%) of consecutive patients treated as outpatients


Home treatment l.jpg

Home treatment

  • Treated all patients except those with massive PE(6), high risk bleed or active bleeding(7), or other reasons for hospitalization (20)

  • ResultsRecurrence3.6%Major bleed2.0% Death 7%

  • No difference - nurse vs. patient injection


Slide46 l.jpg

Columbus vs. Wells

Columbus Wells

Event 5.3% 3.6%

Bleed 3.1% 2.0%

Death 7.1% 7.0%


What about cost l.jpg

What about cost?

  • Hull, et al. evaluated cost per 100 patients for inpatient use

    • LMWH - $335,687 vs. UFH - $375,836

    • Cost savings - $40,149

  • Outpatient therapy augmentscost savings


Summary l.jpg

Summary

  • LMW Heparins are well established for treating DVT

  • Three RCTs have shown LMW heparin to be as effective as UFH in treating PE


Summary49 l.jpg

Summary

  • Enoxaparin is the only LMW heparin that is approved by the FDA for DVT with or without PE

  • LMW heparin has been shown to be cost-effective for treatment both in hospital and out of hospital


Summary50 l.jpg

Summary

  • There is no RCT data regarding home treatment for stable patients with PE or when to discharge from the hospital

  • Seems reasonable to discharge when stable and not hypoxic

  • We may be doing this already since 50% of patients with proximal DVT have silent PE


Further questions l.jpg

Further Questions

  • Are all LMW heparin products equivalent?

  • Is once daily dosing equivalent to twice daily dosing?

  • Is home treatment / early discharge appropriate?


Accp consensus recommendations l.jpg

ACCP Consensus Recommendations

  • Treat with LMWH for at least five days (overlapped with oral anticoagulation) until INR therapeutic for two days (range 2-3)

  • Patients with reversible or time-limited risk factors treated for three to six months. Those with idiopathic DVT treated for six months


Cases revisited l.jpg

Cases Revisited

38 wm with post-op DVT and PE

? UFH or LMWH? Hospital or Home?

  • UFH and LMWH are equivalent

  • No data for sending home


Cases revisited54 l.jpg

Cases Revisited

84 wf with known DVT, suspected PE transferred to renal service

? UFH or LMWH in hospital?

  • UFH and LMWH are equivalent


Cases revisited55 l.jpg

Cases Revisited

25 bf with PE and hypoxia (4L NC)? UFH or LMWH? Discharge when?

  • UFH and LMWH are equivalent

  • No data directing discharge but consider discharging when not hypoxic


Cases revisited56 l.jpg

Cases Revisited

43 wm s/p craniotomy, now with saddle embolus? UFH or LMWH?

  • Treat with unfractionated heparin (massive PE)


Thanks for your help l.jpg

Thanks for your help

  • Dr. Dunagan

  • Amanda Ebright

  • Anne Powers


  • Login