spontane und tumor-assoziierte vte: womit wie … und tumor-assoziierte vte: womit wie lange...
TRANSCRIPT
![Page 1: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/1.jpg)
Spontane und Tumor-assoziierte VTE:
womit wie lange antikoagulieren
Paul Kyrle
Allgemeines Krankenhaus Wien
![Page 2: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/2.jpg)
Disclosures relevant for this presentation
Consultancies, member of advisory boards, speaker fees
Boehringer-IngelheimBayerDaiichi-SankyoBristol Myers SquibbPfizer
![Page 3: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/3.jpg)
Spontane VTE - unprovoked VTE
![Page 4: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/4.jpg)
Unprovoked VTE No provoking risk factor (transient or persistent)
Major transient risk factorsSurgery with general anesthesia for greater than 30 minutesConfined to bed in hospital for at least 3 days with an acute illnessCesarean section
Minor transient risk factorsSurgery with general anesthesia for less than 30 minutesAdmission to hospital for less than 3 days with an acute illnessEstrogen therapy, pregnancy or puerperiumConfined to bed out of hospital for at least 3 days with an acute illnessLeg injury associated with reduced mobility for at least 3 days
Persistent risk factors Active cancer, inflammatory bowel disease
Kearon, Ageno & Kyrle, JTH 2016
Categorization of VTE (unprovoked vs. provoked)
![Page 5: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/5.jpg)
Unprovoked VTE No provoking risk factor (transient or persistent)
Major transient risk factorsSurgery with general anesthesia for greater than 30 minutesConfined to bed in hospital for at least 3 days with an acute illnessCesarean section
Minor transient risk factorsSurgery with general anesthesia for less than 30 minutesAdmission to hospital for less than 3 days with an acute illnessEstrogen therapy, pregnancy or puerperiumConfined to bed out of hospital for at least 3 days with an acute illnessLeg injury associated with reduced mobility for at least 3 days
Persistent risk factors Active cancer, inflammatory bowel disease
Kearon, Ageno & Kyrle, JTH 2016
Categorization of VTE (unprovoked vs. provoked)
![Page 6: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/6.jpg)
Thrombolysis
Anticoagulation
Mechanical thrombus removal
Vena cava filter
Treatment of VTE
![Page 7: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/7.jpg)
Heparin (LMWH) vitamin K antagonists (VKA)
(Heparin ) direct oral anticoagulant (DOAC)
Anticoagulation
![Page 8: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/8.jpg)
TF-FVIIa
FXa
FIIa
FVIIIa, FVa
FIXa
Fibrin
FXIaRivaroxaban
Apixaban
Edoxaban
Dabigatran
courtesy of Ansgar Weltermann, modified
DOAC
![Page 9: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/9.jpg)
DOAC
Rapid onset (~3 hrs)
Rapid offset (t1/2 ~12 hrs)
No food interactions
Few drug interactions
Flat dose/response curve
Why DOAC and not VKA?
VKA
Slow onset
Slow offset
Food interaction
Abundant drug interactions
Steep dose/response curve
Monitoring requiredMonitoring not required
![Page 10: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/10.jpg)
12/2009 - 12/2013:
7 non-inferiority studies
3 superiority studies
32.094 pts
DOAC
![Page 11: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/11.jpg)
DOAC vs. VKA - Overall efficacy
van Es, Blood 2015
RRR 10%
![Page 12: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/12.jpg)
DOAC vs. VKA - Overall major bleeding
van Es, Blood 2015
RRR 39%
![Page 13: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/13.jpg)
Apixaban
Rivaroxaban
Combined0.45 (0.27, 0.77)
Patients > 75 yrs – VTE or VTE-related death
Sandar, JAGS 2014
![Page 14: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/14.jpg)
Dabigatran
Apixaban
Rivaroxaban
Combined1.02 (0.73, 1.43)
Patients > 75 yrs – major or CRNM bleeding
Sandar, JAGS 2014
![Page 15: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/15.jpg)
EnoxaparinHeparin Dabigatran 150 mg BID
Apixaban 5 mg BID **
Rivaroxaban 20 mg OD *
AMPLIFY ( 2013)
HOKUSAI ( 2013) EnoxaparinHeparin Edoxaban 60 mg OD
EINSTEIN DVT, PE (2010)
Treatment of VTE with a DOAC
* 15 mg BID for 3 weeks
** 10 mg BID for 1 week
RE-COVER 1+2 (2009, 2013)
![Page 16: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/16.jpg)
Risk of recurrence in pts with a 1st unprovoked VTE
Kyrle & Eichinger, Lancet 2010
![Page 17: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/17.jpg)
ACCP Guideline
Kearon, Chest 2016
In patients with a first VTE that is an unprovoked
proximal DVT of the leg or PE and who have a low
or moderate bleeding risk, we suggest extended
anticoagulant therapy (no scheduled stop date)
over 3 months of therapy (Grade 2B).
![Page 18: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/18.jpg)
Unprovoked VTE – duration of treatment
Identification of patients with a high recurrence risk
Laboratory thrombophilia screening
Clinical characteristics
Prediction tools
![Page 19: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/19.jpg)
Laboratory thrombophilia screening
Risk factors for 1st rather than 2nd VTE
Studies showing a clinical benefit are lacking
Normal test result in 30% of pts with recurrence
Unwanted medical consequences (over/undertreatment)
Emotional discomfort (patients/relatives)
not warranted
![Page 20: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/20.jpg)
Clinical characteristics
Sex
Site of thrombosis
![Page 21: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/21.jpg)
Likelihood of Recurrent VTE According to Sex
Kyrle, N Engl J Med 2004;350:2558-2563
![Page 22: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/22.jpg)
ACCP Guideline
Kearon, Chest 2016
Remark: Patient sex and D-dimer level measured a
month after stopping anticoagulant therapy may
influence the decision to stop or extend anticoagulant
therapy.
![Page 23: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/23.jpg)
Risk of recurrence in pts with 1st unprovoked VTE
Kyrle, JTH 2016
![Page 24: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/24.jpg)
Risk of recurrence in pts with 1st unprovoked VTE
Kyrle, JTH 2016
![Page 25: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/25.jpg)
Prediction tools
Rodger and coworkers (CMJA 2008)
Vienna Prediction Model (Eichinger Circulation 2010)
DASH (DD, age, sex, hormones; Tosetto JTH 2012)
![Page 26: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/26.jpg)
http:/www.meduniwien.ac.at/user/georg.heinze/zipfile/
Circulation 2010;121:1630-1636 data supplement (free access)
Risk calculator
Vienna Prediction Model
JTH, 2015
![Page 27: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/27.jpg)
Nomogram to predict recurrence:
Vienna Prediction Model
![Page 28: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/28.jpg)
Extended treatment of VTE
VKA (INR 2-3)
Rivaroxaban 20mg tgl.
Dabigatran 2 x 150mg tgl.
Apixaban 2 x 2.5mg tgl.
Edoxaban 1 x 60mg tgl.
![Page 29: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/29.jpg)
Extended treatment of VTE
VKA (INR 2-3)
Rivaroxaban 20mg tgl.
Dabigatran 2 x 150mg tgl.
Apixaban 2 x 2.5mg tgl.
Edoxaban 1 x 60mg tgl.
![Page 30: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/30.jpg)
Cancer-associated VTE
![Page 31: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/31.jpg)
Lee, N Engl J Med 2003; Parpia, Contemporary Clinical Trials 2011
Competing riskKaplan-Meier
HR 0.48; p=0.002
Major bleeding: 6% (LMWH) vs. 4% (VKA), p=0.3
CLOT: dalteparin vs. warfarin in cancer-associated VTE
![Page 32: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/32.jpg)
Clot
Catch
Lee, JAMA 2015;314(7):677-686
CATCH: tinzaparin vs. warfarin in cancer-associated VTE
![Page 33: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/33.jpg)
DOAC in cancer-associated VTE
licenced, but …
guideline panels recommend against their use
no comparison against LMWH
too few pts included in studies
interaction with anti-cancer therapy
reduced absorption from gastrointestinal tract
![Page 34: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/34.jpg)
In “cancer-associated” thrombosis, as long-term (first
3 months) anticoagulant therapy, we suggest LMWH
over VKA therapy (Grade 2B), dabigatran (Grade
2C), rivaroxaban (Grade 2C), apixaban (Grade 2C),
or edoxaban (Grade 2C).
ACCP Guideline
Kearon, Chest 2016
![Page 35: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/35.jpg)
Efficacy
2.0% vs. 2.2% (~ 27.000 patients)
Cancer: 3.4% vs. 5.9% (~ 1.500 patients)
No cancer: 2.4% vs. 2.5%
DOAC vs. VKA in cancer associated VTE
![Page 36: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/36.jpg)
Safety
1.1% vs. 1.8% (~ 27.000 patients)
Cancer: 2.9% vs. 3.7% (~ 1.500 patients)
No Cancer: 0.9% vs. 1.6%
DOAC vs. VKA in cancer associated VTE
![Page 37: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/37.jpg)
Personal approach – drug regimen
LMWH (therapeutic dose, once daily)
acute VTE (first 4 weeks)
during systemic antitumor treatment
vomiting, diarrhea
otherwise DOAC
no VKA
![Page 38: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/38.jpg)
In patients with DVT of the leg or PE and active
cancer and who (i) do not have a high bleeding risk,
we recommend extended anticoagulant therapy (no
scheduled stop date) over 3 months of therapy (Grade
1B), or (ii) have a high bleeding risk, we suggest
extended anticoagulant therapy (no scheduled stop
date) over 3 months of therapy (Grade 2B).
ACCP Guideline
Kearon, Chest 2016
![Page 39: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/39.jpg)
Personal approach – duration
Remission
3 – 6 months
Active cancer
Indefinite
According to bleeding risk and patient preferences
![Page 40: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/40.jpg)
Summary
Unprovoked VTE
DOAC are at least as effective and safe as VKA
Extended anticoagulation should be considerednted, in particular in men with proximal DVT or PE
Cancer-associated VTE
LMWH still first choice
DOAC are a valuable alternative under certain conditions
Duration depends on disease activity and patient preference
![Page 41: Spontane und Tumor-assoziierte VTE: womit wie … und Tumor-assoziierte VTE: womit wie lange antikoagulieren ... pregnancy or puerperium ... Normal test result in 30% of pts with recurrence](https://reader031.vdocuments.mx/reader031/viewer/2022030511/5abba6697f8b9a24028cdff0/html5/thumbnails/41.jpg)
Anticoagulant treatment of VTE: a changing world