Presentation is loading. Please wait.

Presentation is loading. Please wait.

VTE: It’s still a killer in Canada Sam Schulman, MD, PhD Dept. of Medicine McMaster University.

Similar presentations


Presentation on theme: "VTE: It’s still a killer in Canada Sam Schulman, MD, PhD Dept. of Medicine McMaster University."— Presentation transcript:

1 VTE: It’s still a killer in Canada Sam Schulman, MD, PhD Dept. of Medicine McMaster University

2 Faculty/Presenter Disclosure Faculty: Dr. Sam Schulman Program: 51 st Annual Scientific Assembly Relationships with commercial interests: –Grants/Research Support: N/A –Speakers Bureau/Honoraria: Boehringer Ingelheim and Bayer Healthcare for work in study-related committees –Consulting Fees: N/A –Other: N/A

3 Disclosure of Commercial Support This program has received financial support from Boehringer Ingelheim and Bayer Healthcare in the form of Honorarium. This program has received in-kind support from N/A Potential for conflict(s) of interest: –Dr. Sam Schulman has received Honorarium from Bayer Healthcare and Boehringer Ingelheim whose products are being discussed in this program. –Bayer Healthcare and Boehringer Ingelheim sell products that will be discussed in this program: rivaroxaban and dabigatran.

4 Mitigating Potential Bias All treatment alternatives are discussed

5 Contents Case discussion Epidemiological data Who is at the highest risk Extended prophylaxis – when? Diagnosis – missing and overinterpreting Treatment – a lot easier now How long after VTE – a dilemma

6 Unfortunate case 65 y.o. male, fell from ladder. X-rays normal except for L4 burst # on CT No bleeding, Hgb stable Sharp back pain, remains bedridden in hospital. On day 3 urinary problems and weakness in one leg  scheduled for decompression laminectomy next day. SaO2 94-98% all the time Surgery Day 4 in late afternoon. Suspected MI in recovery  arrest. CPR unsuccessful – large PE

7 PE - mortality 10% succumb within 1 h –Usually before arrival at the hospital PE – 3rd leading cause of cardiovascular death

8 Risk factors for VTE Surgery Trauma Immobility, paresis Malignancy Cancer therapy Previous VTE Increasing age Pregnancy / postpartum Estrogens Selective estrogen receptor modulators Acute medical illness Heart or respiratory failure Inflam. bowel disease Nephrotic syndrome Myeloprolif disorders PNH Obesity Smoking Varicose veins Central venous catheter Thrombophilic defect ACCP Guidelines on Antithrombotic and Thrombolytic Therapy

9 Cancellation of Sx day after day – not an uncommon phenomenon Waiting time for hip# Sx often 3 days Typical order: ”NPO for surgery in a.m.”, ”Hold heparin” Heparin or LMWH evening before does not increase bleeding. These patients have to receive LMWH qHS Even neuraxial anesthesia next morning is OK (10-12 h after last dose) American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines, 3rd ed., 2010

10 Postop VTE prophylaxis Necessary if patient not mobilizing within 24 h Bleeding risk – use mechanical devices Otherwise ”chemoprophylaxis” – usually until discharge. Consider extension if patient not mobilizing at that time point Use a risk assessment score, e.g. Caprini Gould MK et al. ACCP Guidelines. CHEST 2012; 141 Suppl: 227-77

11 Data on incidence of VTE Worcester, MA – all medical records 1999 with VTE diagnosis: 104 per 100,000 1 Olmsted County, MN – medical records of all residents with VTE 1966-1990, incl PE on autopsy: 117 per 100,000 2 Sweden – Men born 1913, followed from age 50: 387 per 100,000 3 Bretagne, France – Diagnosis data: 184/100,000 4 1.Spencer FA. J Gen Intern Med 2006 2.Silverstein MD. Arch Intern Med 1998 3.Hansson PO. Arch Intern Med 1997 4.Oger E and EPI-GETBO. Thromb Haemost 2000

12 Survival after VTE Olmsted County inception cohort Followed 1966-1990, n=2218 After7-day30-day1-year DVT96.2%94.5%85.4% PE ±DVT 59.1%55.6%47.7% VTE74.8%72.0%63.6% Risk factors for death PE Age BMI Patient location @ onset Malignancy CHF More risk factors Neurologic disease Chronic lung disease Recent Sx Hormone Rx Smoking tobacco Chron renal disease Heit JA et al. Arch Intern Med 1999;159:445-53

13 Survival after VTE Heit JA et al. Arch Intern Med 1999;159:445-53 >1/3 of deaths were on day of onset/unrecognized VTE

14 Copyright ©2003 American Heart Association White, R. H. Circulation 2003;107:I-4-I-8 Annual incidence of VTE among residents of Worcester MA 1986, by age and sex Effect of age

15 Prevalence of VTE is predicted to double by 2050 VTE = venous thromboembolism Deitelzweig SB et al. Am J Haematol 2011;86:217–20 15 Year VTE cases per 100 000: 20 02 20 03 20 04 20 05 20 06 20 08 20 10 20 1520 20 25 20 30 20 35 20 40 20 45 20 50 31 7 34 1 37 1 40 1 42 2 42 6 43 2 45 3 47 8 50 5 52 7 54 4 55 6 56 3 56 7 Adults 18 years and older with VTE in USA (millions) 0 0.5 1 1.5 2 200220032004200520062008201020152020202520302035204020452050

16 Patients at highest risk Recent VTE Malignancy Spinal cord injury Heparin-induced thrombocytopenia

17 Increased prophylactic dose Spinal cord injury Burn injury Bariatric surgery

18 >100,000 procedures in the US Incidence of reported VTE 0.1% - 1%, fatal PE 0.2% Mainly after discharge 95% of US surgeons give prophylaxis LMWH, UFH tid or fondaparinux: May add mechanical. Higher doses than standard Consecutive patients 1979-2000 Early ambulation & mechanical proph. Group 1: enoxaparin 30 mg bid (n=92) DVT 5.4% Group 2: enoxaparin 40 mg bid (n=389) DVT 0.6% Scholten DJ et al. Obes Surg 2002;12:19-24 Consecutive patients 1979-2000 Early ambulation & mechanical proph. Group 1: enoxaparin 30 mg bid (n=92) DVT 5.4% Group 2: enoxaparin 40 mg bid (n=389) DVT 0.6% Scholten DJ et al. Obes Surg 2002;12:19-24

19 Extended postop prophylaxis, i.e. up to 1 month instead of 1 week 1.High risk of VTE + pelvic/abdominal Sx for cancer (Grade 1B) a)Results in 13 fewer non-fatal events per 1000 without significant increase in bleeding 2.Major orthopedic surgery (THR, TKR, HFS) – minimum 10-14 d (Grade 1B) and suggest up to 35 d (Grade 2B) a)Results in 9 fewer non-fatal events per 1000 without significant increase in bleeding ACCP Guidelines. CHEST 2012; 141 Suppl

20 Spinal cord injury In case of paraplegia: Very high risk at least first month Continued increased risk 3 months Then normalization

21 Logistics not an excuse now LMWH/fondaparinux are parenteral. Rivaroxaban 10 mg or dabigatran 150/220 mg once daily or apixaban 2.5 mg twice daily are available and approved for THR and TKR Effective and safe, cost-effective vs LMWH

22 The Primary Outcomes – Ortho Sx RE-MODELTKRNon-inferior RE-MOBILIZETKRInferior RE-NOVATETHRNon-inferior RE-NOVATE IITHRNon-inferior RECORD 1THRSuperior RECORD 2THRSuperior RECORD 3TKRSuperior RECORD 4TKRSuperior ADVANCE 1TKRNon-inferiority not met ADVANCE 2TKRSuperior ADVANCE 3THRSuperior DabiRivaApixaDabiRivaApixa

23 Suspected DVT / PE

24 Typical case 36 y.o. lady with pain in the R calf x 3d Previously healthy Went for a long walk last weekend Was on COC for 10 years, stopped at age 28, restarted 3 months ago. Physical: Tender calf, no edema or SOB

25

26 Reduction of imaging diagnostics Use Wells’ score and D-dimer – –Only if low score + neg D-dimer will result in No imaging D-dimer: Not useful –In generally ill patients –Shortly after surgery –Differential vs cellulitis –Very elderly (>80) –Long duration of symptoms Active cancer 1 Paralysis, recent immob1 Recently bedridden >2 d1 Localized tenderness1 Calf swelling >3 cm1 Unilat pitting edema1 Collateral superf. veins1 Previous documented DVT1 Alt. Dx at least as likely-2 <2 p – unlikely >2 p - likely Active cancer 1 Paralysis, recent immob1 Recently bedridden >2 d1 Localized tenderness1 Calf swelling >3 cm1 Unilat pitting edema1 Collateral superf. veins1 Previous documented DVT1 Alt. Dx at least as likely-2 <2 p – unlikely >2 p - likely

27 Ultrasound pitfalls Very difficult to tell new from old if no comparison If proximal swelling – ask for iliac and inferior v cava veins Should do both legs even if unilat spt

28 Do we have to treat distal DVT?  Analysis of 5 studies of sympt calf DVT without treatment (Rhigini et al 2006):  Progression proximally in 25 of 353 (7%)  RCT (N=196): VKA alone UFH 5,000 x2 UFH 12,000 x1 Placebo 11% 7%78% 2.3% 0%25% Progression 0-8 w 9-24 w (ultrasound) Belcaro G et al. Minerva Med 1997;88:507-14

29 Calf DVT: Risk factors for progression Positive D-dimer Extensive calf DVT or close to proximal Unprovoked or persistent risk factor Active cancer History of VTE Hospitalized patient Kearon C et al. ACCP Guidelines. CHEST 2012; 141 Suppl

30 Practical approach Treat if very symptomatic or risk factors for extension (Grade 2C) With increasing risk of bleeding – consider not treating – but do serial ultrasound. (Grade 2C) Progression is most common first 2 w. Kearon C et al. ACCP Guidelines. CHEST 2012; 141 Suppl

31

32 Suspected PE Wells’ clinical prediction score for PE Previous PE or DVT+1.5 Heart rate > 100/min+1.5 Recent surgery or immobilization+1.5 Clinical signs of DVT+3 Alternative diagnosis less likely than PE+3 Hemoptysis+1 Cancer+1 Dichotomized rule Unlikely< 4 Likely> 4 Wells PS et al. Thromb Haemost. 2000;83:416-20

33

34 Can my PE-patient in ER go home? Pulmonary Embolism Severity Index (PESI) – Age 1 p / yrSBP <10030 p –Male sex10 pPulse >11020 p –Cancer30 pRR>3020 p –CHF10 pTemp <3620 p –Chron lung dis.10 pSaO2 <90%20 p –  mental status60 p Aujesky D et al. Am J Resp Crit Care Med 2005;172:1041–6 External validation in: J Intern Med 2007;261:597-604 85 p or less = low risk of fatal PE – NPV = 99%

35 Simplified PESI Retrospective analysis of RIETE registry – Age >801 p –History of Cancer 1 p –Chron cardiopulmonary dis.1 p –Pulse >110 1 p –CHF1 p –SBP <100 1 p –SaO2 <90%1 p 0 = low risk, 1 or more = high risk Jiménez D et al. Arch Intern Med. 2010;170:1383-9

36 Simplified PESI result Jiménez D et al. Arch Intern Med. 2010;170:1383-9

37 Initial standard anticoagulation Generally same treatment for DVT and PE (=VTE): –UFH iv – weight adjusted (bolus 80 U/kg, infusion at 18 U/kg/h)* –UFH s.c. 250 U/kg bid * –UFH s.c. 17,500 U bid * –UFH s.c. 333 U/kg 1 st dose, then 250 U/kg bid without monitoring –LMWH s.c. without monitoring –Fondaparinux s.c. 7.5 ±2.5 mg daily –Rivaroxaban 15 mg p.o. BID x 3 w, then 20 mg q.d. – LU-code 444 * Monitored to keep anti-Xa at 0.3-0.7 IU/mL – at 6 h for s.c. 1B

38 FIDO-Study Copyright restrictions may apply. Kearon, C. et al. JAMA 2006;296:935-942. Clinical Outcomes During the Study Period UFH 250 U/kg bid vs LMWH 100 IU/kg bid EventUFHLMWH Recurrence3.8%3.4% Maj Bleed1.7%3.4% Any Bleed8.3%8.5% Death5.2%6.3% EventUFHLMWH Recurrence3.8%3.4% Maj Bleed1.7%3.4% Any Bleed8.3%8.5% Death5.2%6.3%

39 UFH sc in renal failure Increased risk of bleeding with any anticoagulant – NOACS, warfarin, LMWH, heparin Lack of good studies but reduce dose for –NOACS, LMWH and UFH UFH sc protocol @ Hamilton for CrCl <30 –1 st dose 250 IU per kg –Then 200 IU per kg q 12 h.

40 EINSTEIN-DVT Objectively confirmed DVT without symptomatic PE EINSTEIN-PE Objectively confirmed PE with or without symptomatic DVT R Predefined treatment period of 3, 6, 12 months Rivaroxaban 15 mg twice daily Rivaroxaban 20mg once daily Randomisation Eligible patients N~2900 N~3300 Enoxaparin twice daily for at least 5 days, plus VKA target INR 2.5 (INR range 2–3) Day 1 Day 21 Day 30 after last dose DVT=deep vein thrombosis; INR=international normalised ratio; LMWH=low molecular weight heparin PE=pulmonary embolism; VKA=vitamin K antagonist Oral Factor Xa inhibitor, rivaroxaban: EINSTEIN-DVT/PE

41 Rivaroxaban – a new option Einstein DVT Bauersachs R et al.NEJM 2010; 363: 2499-510 Major or clinically relevant bleeding in 8.1% per group

42 Rivaroxaban – a new option Einstein PE Major or clinically relevant bleeding in 10.3% (riva) vs. 11.4% (standard Rx) Büller HR et al. NEJM 2012

43 Caveats for rivaroxaban Not for severe renal dysfunction (calc CrCl <30 mL/min) Few of the study patients hade extensive DVT or large PE. These patients might benefit from intial parenteral Rx. Dose change at 3 weeks (15 mg BID  20 mg q.d.) Dose with food – more reliable absorption

44 Standard duration of anticoagulation is now 3 m. Schulman S et al. N Engl J Med 1995; 332: 1661-5 Kearon C et al. N Engl J Med 1999; 340: 901-6 6 months? 27 months? 1A

45 WODIT Agnelli et al. NEJM 2001

46 Recurrent DVT after stopping Patients with unprovoked DVT –3 months Rx – 10% first year after (WODIT) –6 months Rx – 10% first year after (DURAC) –12 months Rx – 10% first year after (WODIT) –24 months Rx – 10% first year after (LAFIT) No difference 3 vs 6 months in patients with proximal DVT or PE in DOTAVK Pinede et al: Circulation; May 27, 2001 (DOTAVK)

47 PE as a risk factor Pinede et al. ASH 2003 A meta-analysis on individual data N=2474

48 Decision on long-term at 3 m Long-term treatment for –Unprovoked VTE –Second episode –Cancer Unless bleeding risk or adequate monitoring unavailable 1B

49 Suggestions for duration of VKA Proximal DVT and permanent risk or PE 3 m 6 m 12 m 24 m Indefinitely Bleeding, Poor compliance Old age Needs ASA Female? Mild thrombophilic defect / Second VTE Third VTE or more, Severe thrombophilia, Severe venous insuff., Pulmonary hypertension Patient preferences

50 Or … Provoked and small DVT or small PE: 3 m Unprovoked small DVT: 3 m Unprovoked extensive DVT: 6 m Unprovoked extensive PE: 1 y

51 Elevated D-dimer

52 Management strategy – unprovoked VTE Dx 0 3-6 m +1 m D-dimer Pos Neg Pos 8.9%/yr Neg Neg 3.5%/yr Verhovsek M. Ann Intern Med. 2008;149:481-90

53 D-dimer in males Several studies indicate that males have despite normalization of D-dimer a higher risk of recurrence.

54 Conclusions Several risk scores and risk stratification tools are available and should be used Diagnostic algorithm for DVT/PE is helpful Many options for treatment of VTE exist Decide at 3-6 months regarding stopping or indefinite anticoagulation Extended postoperative prophylaxis after THR, TKR, HFS and abdominal/pelvic Sx for cancer


Download ppt "VTE: It’s still a killer in Canada Sam Schulman, MD, PhD Dept. of Medicine McMaster University."

Similar presentations


Ads by Google