Presentation on theme: "2013 Update on Venous Thromboembolism University of North Carolina"— Presentation transcript:
1 2013 Update on Venous Thromboembolism University of North Carolina 452013 Update on Venous ThromboembolismStephan Moll, MDUniversity of North CarolinaChapel Hill, NCAdvocate Lutheran General Hospital; Park Ride, IL,March 2nd, 2013
3 The 3 Major Developments in 2012 Publication of ACCP Guidelines 2012IApproval of Rivaroxaban for VTEIIApproval of Apixaban for atrial fibrillationIII
4 Patient Diagnosis few days later 3 mo any time Q1: Outpatient or inpatient?
5 Case - PE HPI 63 year old man, quite healthy 4 days h/o moderate CP + SOB; now SOB with 1 flight of stairs.No leg symptomsNo preceding trauma, immobility, surgery, long-distance travelArthroscopic knee surg 2 yrs agoHTN; Obesity (BMI 32.3)No h/o cancer; no h/o bleedingPMHNegative for VTEFH
6 Case Physical Exam BP 135/87; P 92 / min RR at rest 16 min, not SOB when talking; O2 on RA 93 %BMI 32.3; lungs clear; legs R=LCTA chestRUL segmental PE, L UL and LL subsegmental PE
7 Question – Outpatient vs. Inpatient? DiagnosisUnprovoked PE. VTE risk factors: (a) obesity.How to manage this patient?Outpatient?Admit?
8 ACCP 2012Recommend home treatment for DVT (1B) and early d/c for low-risk PE. (2B).Acute Treatment[Kearon C et al. Chest 2012;141(2)(Suppl):e419S-e494S]
9 Outpatient vs. Inpatient – HESTIA Criteria 1. Hemodynamically unstable?2. Thrombolysis or embolectomy needed?3. Active bleeding or high risk of bleeding?4. Oxygen needed to keep O2 saturation > 90 % for > 24 hrs?5. PE dx’d during anticoagulant therapy?6. iv pain meds for > 24 hrs?7. Medical or social reason for admission?8. GFR < 30 ml/min?9. Severe liver impairment?10. Pregnant?11. Documented h/o HIT?Hestia (Greek) = home and hearth. She is the goddess of the hearth, architecture, and the right ordering of domesticity, the family and the state.[Zondag W et al. J Thromb Haemost 2011;9:1500-7][Zondag W et al. J Thromb Haemost 2013(Jan 6th )ePub]
10 PESI = Pulmonary Embolism Severity Index [Aujesky D et al. Am J Respir Crit Care Med 2005;15;172(8):1041-6]
11 Outpatient vs. Inpatient – HESTIA Score Teaching point #1Outpatient PE managementSuitable for, may be, 50 % of PE patients;HESTIA criteria can be useful for decision making.
12 Patient Diagnosis few days later 3 mo any time Q1: Outpatient or inpatient?Q2:Thrombolytics?
13 Thrombolytics?For PE, with hypotension or high risk for hypotension: suggest thrombolytics, systemically. 2CFor DVT, suggest anticoagulant therapy alone over thrombolysis (catheter-directed or systemic). 2C[Kearon C et al. Chest 2012;141(2)(Suppl):e419S-e494S]
14 PE: Indicators of Poor Outcome ESC criteria (based on consensus; lack of validation)CriteriamortalityHigh riskCardiovascular shock or persistent hypotension> 30 %Intermediate riskLab (troponin, BNP) or RV dysfunction1-30 %Low risknl labs (troponin, BNP); nl RV function< 1 %[Torbicki A et al. Eur Heart J 2008; ]
15 Thrombolytics?PEITHO trial: 1,006 patients with RV stain PLUS pos. troponin: thrombolytics versus placebo; results spring 2013.ATTRACT trial 392/692 patients enrolled as of Jan 8th, 2013.[http://clinicaltrials.gov/ct2/show/NCT ?term=peitho&rank=1][http://clinicaltrials.gov/ct2/show/NCT ?term=ATTRACT&rank=1]
16 Patient Diagnosis few days later 3 mo any time Q1: Outpatient or inpatient?Q2:Thrombolytics?Q3:LMWH/warfarin or rivaroxaban?
17 Question –Anticoagulant Choice Outpatient management is chosen. CBC, PT, aPTT normal; Creatinine 0.95; liver enzymes normal. How would you treat?LMWH or fondaparinux / warfarinRivaroxaban (Xarelto)Dabigatran (Pradaxa)Apixaban (Eliquis)
18 New Oral Anticoagulants DabigatranRivaroxabanApixabantmaxhrs2 - 4 hrs1 - 3 hrsHalf lifehrshrs8 - 15hrsRenal excretion80%66 %ca. 25 %FDA approvalA. fibVTE preventionVTE treatment[Garcia D et al. Blood Jan 7;115(1): Review]In clinical development: Edoxaban, Betrixaban (not FDA approved)
19 Rivaroxaban in Acute DVT and PE A. DVT studyB. PE study[Bueller H et al. NEJM 2010;363: ][Bueller H et al. NEJM 2012;366: ]19
20 RivaroxabanBLEEDINGClinically relevant bleeding (composite of major and clinically relevant non-major bleeding): Same.Major bleeding: Same (DVT study) or less (PE study).[Bueller H et al. NEJM 2010;363: ][Bueller H et al. NEJM 2012;366: ]Nov 201220
21 Rivaroxaban In which patient do I consider rivaroxaban? Acute DVT or PEAll patients treated as outpatientsMild to moderate DVT; HESTIA criteria for PEOn long-term warfarinI discuss it with all patientsFluctuating INRs, high “warfarin hate factor”21
22 Rivaroxaban In which patient would I NOT use rivaroxaban? Renal impairment: GFR < 30 ml/min (or 40; “buffer zone”) by Cockroft-GaultLiver diseaseIncreased bleeding risk; particularly GI bleedingAcute cerebral vein thrombosisBMI > 40 or “low” body weightCancerPatient who doesn’t like idea of “no known reversal agent/strategy”.(140-age) x kg / serum creatinine x 0.85 for women22
23 Rivaroxaban Things to consider when starting rivaroxaban LABS: CBC, creatinine, AST, ALT, t. biliGFR > 30 ml/minCheck with insurance carrier ($ 335 / month)15 mg bid for 3 weeks, then 20 mg qdTake with food (AM or PM)Drug interactions: HIV meds, antifungal, sz drugs, St. John’s wortF/u with you in 3 weeks and in 3 months, then yearly.23
24 Rivaroxaban Teaching point #2 Acute or previous VTE: Rivaroxaban is a possible treatment option.Teaching point #224
26 Apixaban in Atrial Fibrillation [Granger CB et al. N Engl J Med 2011;365:981-92]26
27 Apixaban in Atrial Fibrillation is MORE effective than warfarinleads to LESS major bleeding.Dec 201227
28 Hospital Guide for New Oral Anticoagulants Dabigatran:Rivaroxaban:Apixaban:Comprehensive management documents: : UNC and rivaroxabanTeaching Point #328
29 New Oral Anticoagulants: Cost Per day: $ 9.20 to $ (ca. $ /day)Per month: $ to (ca. $ /mo)QtyAWP *CVSWalgreensWalmartApixaban 5 mg bid60$300.44$335.99$308.99$276.16Rivaroxaban 20 mg qd30$300.42$324.99$281.46Dabigatran 150 mg bid$330.99$303.99$286.32[personal communciations: evaluation of Average Wholesale Price (AWP) and inquiry from 3 national pharmacy chains; Jan 28, 2013]29
32 Patient Diagnosis few days later 3 mo any time Q1: Outpatient or inpatient?Q4:Compression stockings?Q2:Thrombolytics?Q3:LMWH/warfarin or rivaroxaban?
33 Compression Stockings? SOX trial[Kahn SR;ASH 2012;abstract 393]Compression stockings probably/possibly do not prevent PTS.Teaching point #5
34 Patient Diagnosis few days later 3 mo any time Q1: Outpatient or inpatient?Q4:Compression stockings?Q5:D/c anticoag or long-term?Q2:Thrombolytics?Q3:LMWH/warfarin or rivaroxaban?
35 How Long To Treat With Anticoagulation? VTE due to transient risk factor3 monthsWoman with DVT or PE, hormonesWoman with DVT, not hormonesStrong Thrombophilia- D-dimer +Woman with PEMan with DVTLong-termMan with PEOther risk factors for recurrence: Obesity?; age?Other considerations: Bleeding, fluctuating INRs, lifestyle impact, pt preference
36 How Long to Treat with Anticoagulation? [Palareti G et al. NEJM 2006;355:1780-9][Verhovsek M et al. Systematic review on D-dimer to predict recurrent VTE. Ann Int Med 2008;149(7):481‐490]36
37 VTE Recurrence – Risk Assessment Scores HERDOO-2 score[Rodger M et al; CMAJ 2008;179: ]DASH score[Tosetto A et al. J Thromb Haemost 2012 Jun;10(6): ]
38 How Long to Treat With Warfarin? - HERDOO-2 WomenConclusion:Women ≤ 1 d/c anticoagulation.Men, no matter what the score, need to continue anticoagulation.HERDOO-2 ruleHER =Hyperpigmentation orEdema orRednessD = D-dimer positivity (on warfarin)O= obesity, BMI ≥ 30O = Older age, ≥ 65 yrs2 = score of ≥ 2: continue warfarin[Rodger M et al; CMAJ 2008;179: ]
39 How Long to Treat With Warfarin? - DASH DASH scoreD = D-dimer pos (off warfarin) + 2A = age < 50 yearsS = sex (male)H = hormone useConclusion:Score ≤ 1: d/c anticoagulationSummary: The DASH score (details described below) can separate patients with unprovoked VTE into those with a low risk of recurrence in whom anticoagulation can be discontinued after few months of treatment, and those who should be on long-term anticoagulation because of a high risk of recurrence (abstract #544). However, at this point I would not use the DASH score for clinical decision-making.Details: The authors performed a meta-analysis of 7 prospective studies of patients with unprovoked DVT who had been treated for at least 3 months with vitamin K antagonists, and determined what characteristics were indicators of a high risk of recurrent VTE. Main predictors of recurrence were abnormal D-dimer after stopping anticoagulation, age < 50 years, male gender, and VTE not associated with hormonal therapy. A predictive recurrence score was then created – “DASH score” (D-dimer, Age, Sex, Hormones) -, with the following points: (a) +2 for abnormal post-anticoagulation D-dimer, (b) +1 for age < 50 years, (c) +1 for male gender, (d) -2 for hormone use. The annual recurrence rate was: 3.1 % for DASH score ≤1; 6.4 % for DASH score of 2; 12.3 % for score of ≥ 3. As the risk of recurrence is low with a DASH score of ≤1, these are patients with unprovoked VTE in whom long-term anticoagulation is not needed. These are about 50 % of patients with unprovoked VTE. The DASH score needs to be validated. In addition, a discrepancy with another existing scoring system - the HERDOO-2 score (also not validated) - needs to be resolved. The discrepancy is that in the DASH score a younger age (< 50 years) is a predictor of recurrence, whereas in the HERDOO-2 score age > 70 years predicts a higher risk of recurrence. So, it is not clear at this point whether it is worse to be young or old when it comes to VTE recurrence risk.Annual VTE recurrence rate:≤ 1: %2: %≥ 3: %[Tosetto A et al. J Thromb Haemost 2012 Jun;10(6): ]
41 VTE: Length of Anticoagulation Conglomerate decision of:Risk of recurrent VTE (a)…., (b)…., (c) …..Risk of Bleeding (a)…., (b)…., (c) …..Patient preference “Coumadin hate factor”41
42 ACCP 2012 Guidelines: Highlights Treatment beyond Acute PeriodSurgery-associated DVT/PE: recommend 3 months. (1B)Non-surgical transient risk factor: recommend 3 months over 6 or more months. (1B)Unprovoked DVT/PE and low/intermediate risk for bleeding: suggest extended anticoagulation (2B). High bleeding risk: 3 months (1B).Cancer patient with DVT/PE: recommend/suggest extended therapy. LMWH rather than VKA (2C).[Kearon C et al. Chest 2012;141(2)(Suppl):e419S-e494S]
43 VTE: Length of Anticoagulation Teaching point #6How long to treat with anticoagulation?Risk factors for VTE: (a)…., (b)….., (c)……Risk factors for bleeding: (a)…., (b)….., (c)……Patient preference43
44 Patient Diagnosis few days later 3 mo any time Q1: Outpatient or inpatient?Q4:Compression stockings?Q5:D/c anticoag or long-term?Q2:Thrombolytics?Q6:Warfarin or rivaroxaban?Q3:LMWH/warfarin or rivaroxaban?
45 Rivaroxaban in VTE, Secondary Prophylaxis VTE extension study[Bueller H et al. NEJM 2010;363: ]45
46 Patient Diagnosis few days later 3 mo any time Q1: Outpatient or inpatient?Q4:Compression stockings?Q5:D/c anticoag or long-term?Q2:Thrombolytics?Q6:Warfarin or rivaroxaban?Q3:LMWH/warfarin or rivaroxaban?Q7:Aspirin vs anticoagulant?
47 Aspirin and VTE Prevention A. WARFASA studyplaceboaspirinHR 0.5895% CI 0.36 to 0.93p= 0.02[Becattini C et al; NEJM 2012; 366: ]
48 Aspirin and VTE Prevention B. ASPIRE study[Brighton TA, et al. N Engl J Med Nov 22;367(21): ]
49 Aspirin and VTE Prevention – Meta-Analysis C. Meta-analysis[Brighton TA, et al. N Engl J Med Nov 22;367(21): ]
50 ASA and VTE Teaching point #7 Not clear whether Aspirin prevents recurrent VTE.But it does lead to a net “vascular benefit” (arterial and venous together).Teaching point #7
51 Patient Diagnosis few days later 3 mo any time Q1: Outpatient or inpatient?Q4:Compression stockings?Q5:D/c anticoag or long-term?Q8:SurgeryQ2:Thrombolytics?Q6:Warfarin or rivaroxaban?Q3:LMWH/warfarin or rivaroxaban?Q7:Aspirin vs anticoagulant?
52 When to d/c at Times of Surgery Renal function[CrCl, mL/min]Half-life[hours]When to stop drug before surgery (after last drug dose)Standard bleeding riskHigh bleedingriskDabigatran> 8013 (11-22)24 hrs2-4 d> 50 to ≤ 8015 (12-34)> 30 to ≤ 5018 (13-23)≥ 2 d4 d≤ 3027 (22-35)2-5 d> 5 dRivaroxaban>3012 (11-13)2 d< 30 mL/minUnknownModified after [van Ryn J et al. Thromb Haemost 2010;103: ][UNC treatment guidelines]52
53 When to d/c at Times of Surgery ApixabanNo published data exist on optimal perioperative managementd/c ≥ 24 h or ≥48 h prior standard / high risk proceduresFor all new oral anticoagulants: D/c before surgery: 24 hrs for standard risk surgery; 2-4 d for high risk. Consider renal fx.Teaching point #853
54 Patient Diagnosis few days later 3 mo any time Q1: Outpatient or inpatient?Q4:Compression stockings?Q5:D/c anticoag or long-term?Q8:SurgeryQ9:Major bleedQ2:Thrombolytics?Q6:Warfarin or rivaroxaban?Q3:LMWH/warfarin or rivaroxaban?Q7:Aspirin vs anticoagulant?
55 Major Bleeding – Reversal, Management? Best strategy not knownProblem with existing data:NO meaningful patient data publishedAnimals: Mice and rat tailsHuman volunteers: reversal of coagulation testsEx vivo plasma spiking tests: reversal of coagulation testsMice intracranial bleeding modelZhou 2013 article: rivaroxaban and collagen-induced mice brain injury: FFP, PCC, rVIIa were beneficial.[Zhou W et al. Stroke 2013:44:ePub]
56 Major Bleeding Treatment Options Supportive care! Activated charcoal Hemodialysis for Dabigatran, not for Rivaroxaban or ApixabanNo clotting factor therapy
58 Summary Outpatient VTE management Suitable for, may be, 50 % of PE patients;HESTIA criteria for PE risk can be useful for decision making.Rivaroxaban for VTE (acute; previous): possible treatment option.New oral anticoagulantsStarting the drugs;D/c before surgery (24 h for standard risk; 2-4 d for high risk;Major bleeding management.
59 Summary VTE Patient brochure available Compression stockings probably/possibly do not prevent PTS.How long to treat with anticoagulation?Risk factors for VTE: (a)…., (b)….., (c)……Risk factors for bleeding: (a)…., (b)….., (c)……7. Aspirin: Not clear whether it prevents recurrent VTE. I do encourage the use.