New Developments in VTE Treatment South/Sat_Room3_1400... · Optional additional slides: 4...
Transcript of New Developments in VTE Treatment South/Sat_Room3_1400... · Optional additional slides: 4...
New Developments
in
VTE Treatment
GPCME meeting, August, Dunedin
Dr Mark Smith
Haematologist
CDHB Christchurch
Disclosures:
• Accommodation at this meeting funded by Boehringer
• Investigator in phase III studies of Rivaroxiban, Dabigatran, Edoxaban
Clotting factor production & Warfarin effect
Clotting Protein Structure and Inhibitory Drugs
Lane DA et al. Blood 2005;106:2605-2612
ThrombinFactor Xa
Rivaroxaban (Bayer-Schering)
Edoxaban (Daiichi Sankyo)
Apixaban (BMS, Pfizer)
Dabigatran (Boehringer)
Pathway to clot
XII
XI
I (fibrin clot)
II
X
VII
IX
VIII
V
Pathway to clot
XII
XI
I (fibrin clot)
II
X
VII
IX
VIII
V
Pathway to clot
XII
XI
I (fibrin clot)
II
X
VII
IX
VIII
V
Pathway to clot
XII
XI
I (fibrin clot)
II
X
VII
IX
DabigatranAnti-thrombin
VIII
VProteins C & S
Rivaroxiban
Pathway to clot
XII
XI
I (fibrin clot)
II
X
VII
IX
DabigatranAnti-thrombin
VIII
VProteins C & S
Rivaroxiban
NOAC v warfarin
Photo: Art Widak, Dublin,
Ireland
Efficacy
Safety
NOAC v warfarin
Van Der Hulle et al. J Thromb Haemostat. 2014;12:320-328
Efficacy
Safety
Major BleedingDabigatran or Warfarin
• 1121 major bleeds in 1034 patients in 5 phase III studies
• 27,419 patients
• Dabigatran bleeds:
• 627 of 16,755 (3.74%) (warfarin 4.07%)
• Older (75 years v 71 years)
• lower CrCl (53 v 62)
• more use of aspirin (32 v 24%)
Majeed et al. Circulation. 2013;128:2325-2332
NOAC safety in renal failure:
9 Phase III studies, NOAC v warfarin, n=12,272
Lega et al. J Thromb Haemostat. 2014;12:337-343
Efficacy
Lega et al. J Thromb Haemostat. 2014;12:337-343
Safety
NOAC safety in renal failure:
9 Phase III studies, NOAC v warfarin, n=12,272
Routine Clinical Practise Experience
• Patient selection from Hutt Hospital and two primary
care practices, July 2011 – April 2012
• n=92
• At median of 8 months, 70% still taking Dabigatran
• Different from RE-LY at 12 months (p=0.0002)
• Commonest reason for discontinuation GI side effects
• Majority stopped within a few days
• SAE rate for Dabigatran low
Thorne et al. Int Med J. 2014;44:261-65
GI symptomsno antidote
renal function
MI
GP referral:
Male, 46 yearsDuration of anticoagulation?
• Right leg DVT 2013, provoked, 3/12 Rivaroxiban
• Heterozygous FV Leiden
• Now presents with recurrent right leg DVT
provoked by flight from Japan
• Duration of anticoagulation?
GP referral:
Male, 57 yearsDuration of anticoagulation?
• PE February 2014, unprovoked
• Past history:
• High grade lymphoma 1972
• GORD, HTN, chronic fatigue
• Meds:
• Quetiapine, omeprazole, cilazapril, bendrofluazide,
citalopram
• Uncertain if thrombophilia screen done, to help
with decision about long tem anticoagulation
• Duration of anticoagulation?
Eichinger S et al. J Am Heart Assoc 2014;3:e000467
Cumulative VTE recurrence rate after first unprovoked VTE(95% confidence interval)
Male, 48 yearsAdjusting anticoagulation to fit lifestyle
• Motorbike enthusiast
• Pulmonary Embolism 2013, unprovoked
• Duration of anticoagulation?
Male, 48 yearsAdjusting anticoagulation to fit lifestyle
• Motorbike enthusiast
• Pulmonary Embolism 2013, unprovoked
• Duration of anticoagulation?
• Recommended life long warfarin• Declined, stopped warfarin after 6 months
• MVA Jan 2014 (2 months after stopping warfarin)
• Is it safe to remain off anticoagulation?
• Is there a role for D-dimer testing?
Is there a role for D-dimer testing?
Cosmi et al. BLOOD 2010;115:481-488
GP referral:
Female, 42 yearsDuration of anticoagulation?
• Female, 42 years, mother of two (6 and 2 years)
• PE 2013, unprovoked (on OCP)
• Past history:• Polycystic Ovary Syndrome
• Meds:• OCP, spironolactone, metformin, nattokinase (a Japanese soy
extract remedy purported to have fibrinolytic activity)
• ACCP estimated risk:• 10% clot recurrence over 2 years
• Duration of anticoagulation?
• Was the use of estrogen relevant?
Risk of recurrence of estrogen-associated VTE:
a prospective cohort study
Eischer et al. J Thrombosis Haemostasis 2014;12(5):635-640
Anticoagulant
stopped
17%
7%
18%
14%
HRT
D-dimer after first unprovoked VTE:
clot recurrence rate
• Methods: patients <75 years (n=410, 51 years, 44% females), D-dimer while on anticoagulants, and 1 month after stopping.
• Results: 318 remained off anticoagulant therapy; recurrence rate: 5.6% per year
Kearon et al, ISTH 2013
D-dimer after first unprovoked VTE:
clot recurrence rate
• Methods: patients <75 years (n=410, 51 years, 44% females), D-dimer while on anticoagulants, and 1 month after stopping.
• Results: 318 remained off anticoagulant therapy; recurrence rate: 5.6% per year
• Males: 8.2% per year
• Females: 3.9% per year (initial VTE not associated with estrogens)
• Females: 0% per year (initial VTE associated with estrogens)
Kearon et al, ISTH 2013
D-dimer after first unprovoked VTE:
clot recurrence rate
• Methods: patients <75 years (n=410, 51 years, 44% females), D-dimer while on anticoagulants, and 1 month after stopping.
• Results: 318 remained off anticoagulant therapy; recurrence rate: 5.6% per year
• Males: 8.2% per year
• Females: 3.9% per year (initial VTE not associated with estrogens)
• Females: 0% per year (initial VTE associated with estrogens)
• Conclusion: negative D-dimer does not justify stopping anticoagulants after 3-7
months in men
• Risk of recurrent VTE in women low enough to justify stopping anticoagulants
after 3-7 months.
Kearon et al, ISTH 2013
5 year recurrence rate calculation:from 3 weeks after end of anticoagulation (baseline) by use of sex, location of venous
thromboembolism, and d‐dimer
Eichinger S et al. J Am Heart Assoc 2014;3:e000467
http://cemsiis.meduniwien.ac.at/en/kb/science-research/software/clinical-
software/recurrent-vte/
Annual recurrence rate calculation:DASH score: D‐dimer, Age, Sex and Hormone use
Tosetto et al. J Thrombosis and Haemostasis 2012;6:1019-1025
Optional additional slides: 1
• Female, 74 years• Atrial fibrillation
• Systolic murmur
• Echo shows:• Mild-moderate AS
• Mild-moderate MR
• Trivial TR
• Should a NOAC be prescribed?
• “Valvular AF”:• Prosthetic mitral valve
• Mitral stenosis
NEJM 2013
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• What is the landscape for SVT?
• 171 cases annually (incidence 0.64%)
• Concomitant DVT: 24%
• Concomitant PE: 5%
Frappe et al. J Thrombosis and Haemostasis 2014;12:831-8
Optional additional slides: 4
• Association between thyroxine and VTE:
• High FT4 associates with increased clot factors
• Natural anticoagulants unchanged
• High FT4 associates with increased clot risk
• Clinical hyperthyroidism: OR of 17%
Debij et al. J Thrombosis and Haemostasis 2014;12:839-46
New Developments in VTE TreatmentSummary:
• NOACs are safe and effective
• Beware vulnerable patients:
• >75 years, < 50kg, CrCl < 30ml/min (ABC)
• Concurrent aspirin use
• Clot recurrence risk is influenced by:
• Clot provocation (including OCP), gender, d-dimer, age
• Relevance of thrombophilia testing:
• Consider for age less than 40 years
• Consider for pregnancy loss
Pregnancy matters
• 42 Argentine males from couples with unexplained recurrent pregnancy loss
• FV Leiden compared to male controls
• 16% v 3%, OR 6.5% (95% CI 2-20)
Udry et al. J Thrombosis Haemostasis 2014;12(5):666-9
Thank you
Enjoy your meeting
Enjoy Dunedin…