Rapid Fire-Top Articles You Need to Know

Rapid Fire-Top Articles You Need to Know TRACY MINICHIELLO, MD CHIEF, ANTICOAGULATION& THROMBOSIS SERVICE- SAN FRANCISCO VAMC PROFESSOR OF MEDICINE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

Financial Disclosures-NONE

THESE SHOULD BE AT YOUR FINGERTIPS Kearon et al. Chest. 2016;149(2):315-352. Dohert yju et al. JACC 2017

Volume 41, Issue 1, January 2016 Special Issue: Management of Venous Thromboembolism: Clinical Guidance from the Anticoagulation Forum

Secondary Prevention of VTE A 57 year old man with DVT 6 months ago possibly mildly provoked (weeks after 4 hour plane flight) is on rivaroxaban 20 mg daily. For ongoing VTE prevention you recommend: 1) Continue rivaroxaban 20 mg po daily 2) Transition to rivaroxaban 10 mg po daily 3) Switch to apixaban 2.5 mg twice daily 4) Stop rivaroxaban 5) Stop rivaroxaban. Start ASA 81 mg po daily 6) Did you say happy hour?

Duration of Anticoagulation for VTE: 2016 CHEST and AC Forum Guidelines/Guidance Indication CHEST 2016 1 AC Forum 2016 2 1st provoked VTE 3 mo 3 mo (surgical) a 3 mo (medical) 1st unprovoked VTE Extended b Extended 2nd unprovoked VTE Extended b Extended VTE + cancer Extended b Extended a Unless risk factors for recurrence persist b No scheduled stop date, unless high bleeding risk. 1. Kearon C et al. Chest. 2016;149(2):315-352. 2. Streiff MB et al. J Thromb Thrombolysis. 2016;41:32-67. 7

Options for Secondary Prevention of VTE Agent Risk Reduction Regimen None 0% Full-dose anticoagulation 1-3 ~80-90% Warfarin INR 2 3; maintenance dosing dabigatran, rivaroxaban, apixaban, edoxaban Low dose DOAC₂ ~80% Apixaban 2.5 mg BID Low-intensity warfarin 3 75% Warfarin INR 1.5 1.9 ASA 4 32% 100 mg po daily CHEST 2016: In patients with an unprovoked proximal VTE who are stopping anticoagulant therapy and do not have a contraindication to ASA we suggest ASA..to prevent recurrent VTE 1. Agnelli G et al. N Engl J Med. 2013;368:699-708. 2. EINSTEIN INVESTIGATORS N Engl J Med 363;26 3. Kearon C et al. N Engl J Med. 2003;349:631-639. 4. Brighton TA et al. N Engl J Med. 2012;367:1979-1987. 8

8.8% 1.7% Agnelli etal NEJM 2013

After 6-12 months of anticoagulation for VTE Provoked (~60%) or unprovoked (~40%) Clinical equipose about indefinite AC therapy One year follow up Weitz et al. N Engl J Med March 2017

Weitz et al. N Engl J Med March 2017 Rivaroxaban 20 mg Rivaroxaban 10 mg All Provoked VTE Recurrent VTE BLEED 1.5% 1.4% 1.5% 3.3% 1.2% 0.9% 1.0% 2.4% ASA 81 mg 4.4% 3.6% 8.8% 2.0%

Secondary Prevention of VTE A 57 year old man with Extending DVT 6 treatment months ago beyond possibly 3 months could be considered mildly provoked (weeks after 4 hour plane flight) is on with provoked VTE.The rivaroxaban 20 mg daily. results For of this ongoing trail cannot VTE prevention be you recommend: extended to patients who have 1) Continue rivaroxaban an unequivocal 20 mg poindication daily for long-term anticoagulation 2) Transition to rivaroxaban 10 therapy mg po daily 3) Switch to apixaban 2.5 mg twice daily 4) Stop rivaroxaban 5) Stop rivaroxaban. Start ASA 81 mg po daily 6) Did you say happy hour?

What To Do After the Bleed 76 y/o man with CAD (NSTEMI 2006), AFIB CHADS- Vasc=4 on warfarin and ASA is admitted with UGIB. INR is 3.0. He requires 3u PRBCs, vit K and FFP. EGD shows peptic ulcer disease. He is started on high dose PPI therapy, bx for H Pylori done. When should his anticoagulation be restarted? a) Never b) In two weeks c) In three months d) Let the primary provider deal with this one

What To Do After the Bleed Witt Hematology 2016

What To Do After the Bleed 76 y/o man with CAD (NSTEMI 2006), AFIB CHADS- Vasc=4 on warfarin and ASA is admitted with UGIB. INR is 3.0. He requires 3u PRBCs, vit K and FFP. EGD shows peptic ulcer disease. He is started Two weeks on high may dose provide PPI the best balance among GI therapy, bx for H Pylori done. bleed When recurrence should his, anticoagulation be restarted? thromboembolism and a) Never mortality b) In two weeks c) In three months d) Let the primary provider deal with this one

DOACs in Extremes of Weight A 56 year old obese man, BMI 42, weight 155 kg presents with bilateral lower extremity swelling. D-Dimer is elevated prompting bilateral lower extremity ultrasound. Ultrasound shows a DVT in LEFT common femoral, superficial femoral and popliteal vein. He is deemed appropriate for outpatient management of this VTE. What anticoagulant regimen do you recommend? 1. Rivaroxaban 15 mg BID x21 days then 20 mg daily 2. Apixaban 10 mg BID x 7 days then 5 mg BID 3. Enoxaparin bridging to warfarin 4. Admission for IV heparin bridging to warfarin 5. Do you have Ann Wittkowsky s cell phone number?

DOACs in Extremes of Weight Systematic review of 6 trials of DOACS vs warfarin n VTE Proportion of patient s classified as high body weight 15-28% Variability may be related to definition (ie > 90kg vs 100kg) Very little information on extreme body weight (eg < 40 kg, > 150 kg Di Minno MN et al. Ann Med. 2015 Feb;47(1):61-8

DOACS AND EXTREMES OF WEIGHT HIGH BODY WEIGHT NORMAL BODY WEIGHT LOW BODY WEIGHT Minno et al Ann Intern Med 2015 Feb;47(1):61-8

DOACs in Obesity Reduced exposure, lower peaks, shorter t 1/2 Martin et al Journal of Thrombosis and Haemostasis, 2016 14: 1308 1313

DOACs in Extremes of Weight ISTH RECOMMENDATIONS: Recommend standard dosing if BMI< 40 and weight < 120 kg. Suggest DOACS not be used if BMI> 40 or weight > 120 kg If DOACs used in BMI > 40 or weight> 120 kg suggest drug specific peak and trough level If level within expected range continue DOAC; if below suggest warfarin Martin et al. J Thromb Heamost 2016

DOACs in Extremes of Weight A 56 year old obese man, BMI 42, weight 155 kg presents with bilateral lower extremity swelling. D-Dimer is elevated prompting bilateral lower extremity ultrasound. Ultrasound shows a DVT in LEFT common femoral, superficial femoral and popliteal vein. He is deemed appropriate for outpatient management of this VTE. What anticoagulant regimen do you recommend? 1. Rivaroxaban 15 mg BID x21 days then 20 mg daily 2. Apixaban 10 mg BID x 7 days then 5 mg BID 3. Enoxaparin bridging to warfarin 4. Admission for IV heparin bridging to warfarin 5. Do you have Ann Wittkowsky s cell phone number?

Calf Vein DVT A 37 year old man presents with right calf pain one week after being kicked in calf during a soccer game. On exam right calf is 2 cm> left. U/S shows thrombosis in the peroneal vein. What anticoagulation regimen do you recommend? 1. Rivaroxaban 15 mg BID x 21 days then 20 mg daily to complete 3 months of therapy 2. Prophylactic dosing of LMWH or DOAC 3. No anticoagulation, return in one week for repeat ultrasound of lower extremity. 4. Um, is that a deep vein? The guy sitting next to me wants to know.

Also includes gastroc and soleus veins

Calf Vein DVT-CHEST 2016 Risk factors for extension: d-dimer +, extensive thrombosis close to proximal veins; active cancer, prior VTE, inpatient Kearon et al. Chest. 2016;149(2):315-352.

Calf Vein DVT-CHEST 2016 AC Forum clinical guidance We suggest treatment of distal DVT with anticoagulation versus observation. We suggest a duration of therapy 3 months. Streiff MB et al. J Thromb Thrombolysis. 2016;41:32-67..

Calf Vein DVT 1 st DVT, no cancer, outpatient only 6 weeks LMWH and GCS vs placebo and GCS U/S at 3-7 days and 42 days Outcome progression to proximal DVT or PE No difference in VTE, increased risk of bleeding Righini et al. Lancet Haematol 2016;3: e556 62

Calf Vein DVT A 37 year old man presents with right calf pain on week after being kicked in calf during a soccer game. On exam right calf is 2 cm> left. U/S shows thrombosis in the peroneal vein. What anticoagulation regimen do you recommend? 1. Rivaroxaban 15 mg BID x 21 days then 20 mg daily to complete 3 months of therapy 2. Prophylactic dosing of LMWH or DOAC 3. No anticoagulation, return in one week for repeat ultrasound of lower extremity. 4. Um, is that a deep vein? The guy sitting next to me wants to know.

Superficial Vein Thrombosis A 55 year old woman presents with painful palpable swelling over anterior left thigh. On exam she has a palpable cord concerning for SVT. She has an U/S which shows thrombosis of the greater saphenous vein extending from the calf proximally and terminating 6 cm from the deep femoral vein. What anticoagulant regimen do you recommend? a. Prophylactic fondaparinux b. Prophylactic rivaroxaban c. Full dose DOAC or warfarin d. NSAIDS and ice

Superficial Vein Thrombosis CHEST Guidelines Factors that favor the use of AC : extensive SVT; above the knee, close to saphenofemoral junction; severe symptoms; involvement of the greater saphenous vein; history of VTE or SVT; active cancer; recent surgery In patients with superficial vein thrombosis of the lower limb of at least 5 cm in length, we suggest the use of a prophylactic dose of fondaparinux or LMWH for 45 days over no anticoagulation (Grade 2B). Kearon C et al. Chest. 2012

Superficial Vein Thrombosis >400 pts symptomatic SVT riva 10 mg v fonda 2.5mg Symptomatic above the knee SVT of at least 5 cm length + other risk factor (>65, male,hx VTE, cancer, autoimmune disease, non-varicose veins) No difference in primary efficacy outcome After 6 weeks 7% recurrence risk in high risk patients (v 1.2% in CALISTO)

Superficial Vein Thrombosis A 55 year old woman presents with painful palpable swelling over anterior left thigh. On exam she has a palpable cord concerning for SVT. She has an u/s which shows thrombosis of the greater saphenous vein extending from the calf proximally and terminating 2 cm from the deep femoral vein. What anticoagulant regimen do you recommend? a. Prophylactic fondaparinux b. Prophylactic rivaroxaban c. Full dose DOAC or warfarin d. NSAIDS and ice

Reducing the Hospital Burden of HIT Not uncommon HIT occurs in 5% of those exposed to UFH Risk reduced 10 fold with LMWH High morbidity and mortality Thromboembolic complications 20-50% Expensive

Reducing the Hospital Burden of HIT McGowan KE, et al. Blood. 2016 Apr 21;127(16):1954-9

Avoid Heparin Protocol Systematic replacement of most IV and SQ UFH with SQ LMWH in prophylactic or therapeutic doses (remaining uses of UFH were for hemodialysis, intraoperative use for cardiovascular surgery, ACS) Replacement of heparinized saline in arterial and central venous lines with saline flushes Modification of order sets to exclude UFH options Removal of UFH stores from most nursing units. McGowan KE, et al. Blood. 2016 Apr 21;127(16):1954-9

Avoid Heparin Protocol ~40% reduction in suspected HIT ~80% reduction in HIT ~80% reduction in HIT related costs McGowan KE, et al. Blood. 2016 Apr 21;127(16):1954-9

Periprocedural Management of DOACs A 62 year old man with DM, CAD and aflutter is on dabigatran for stroke prevention. He is to undergo ablation procedure next month. He asks if he will need to stop his dabigatran prior to his procedure. What do you tell him? 1) Yes-hold 2 doses prior to the procedure 2) No-you don t have to stop it, just cross your fingers that it all goes ok.

Raval et al. Circulation. 2017;135:00 00

Calkins et al. N Engl J Med. 2017 Mar 19

Uninterrupted Dabigatran v. Warfarin Ablation 77% reduction in risk of major bleeding Calkins et al. N Engl J Med. 2017 Mar 19

Periprocedural Management of DOACs A 62 year old man with DM, CAD and aflutter is on dabigatran for stroke prevention. He is to undergo ablation procedure next month. He asks if he will need to stop his dabigatran prior to his procedure. What do you tell him? 1) Yes-hold 2 doses prior to the procedure 2) No-you don t have to stop it, just cross your fingers that it all goes ok.

Take Home Points Low dose rivaroxaban is an option for secondary prevention of VTE If decision is made to restart anticoagulation after GIB in patients on warfarin for AFIB, reinitiate warfarin on day 7-14 Consider withholding anticoagulation and opting for follow up U/S in low risk calf vein thrombosis 6 weeks of low dose rivaroxaban is an option for treatment of SVT-consider longer duration if high risk Uninterrupted dabigatran appears safe in patients undergoing ablation

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