Duration of Anticoagulant Therapy Linda R. Kelly PharmD, PhC, CACP September 17, 2016
Conflicts of Interest No conflicts of interest to report
Objectives At the end of the program participants will be able to: Design an evidence-based plan for duration of anticoagulation therapy Assess various prediction models for recurrence of VTE Evaluate the utility of testing for hypercoagulability and residual vein thrombosis Discuss the role of aspirin in secondary VTE prophylaxis
5-year rate of recurrence 3% if provoked by surgery 15% for non-surgically provoked
Provoked by Surgery Surgery within 3 months prior to VTE Risk of recurrence in 5 years is about 3%. 3 months of anticoagulation is recommended Kearon Chest 2016 Kearon JTH 2016 Ageno Thromb Res 2015 Streiff J Thromb Thrombolysis 2016
Non-Surgical Transient Risk Factor In general, 3 month of anticoagulation therapy is recommended Estrogen therapy associated Treat for at least 3 months after therapy is stopped Pregnancy associated Treat for least 3 months for the duration of pregnancy and up to 12 weeks post partum Medical illness associated At least 3 months or until illness is resolved Whichever is longer Travel associated Length of travel most important risk factor rather than the mode of travel Chest 2016 specifies flights of more than 8 hours 3 months of anticoagulation is recommended Kearon Chest 2016 Ageno Thromb Res 2015 Streiff J Thromb Thrombolysis 2016
Annualized rate of recurrence 15% per year NCCN Guidelines 2016 Streiff J Thromb Thrombolysis 2016 Khorana J Thromb Thrombolysis 2016
Duration of Therapy Cancer Associated DVT Of Leg or PE Extended treatment is recommended regardless of bleeding risk Until active cancer is resolved Kearon Chest 2016 van der Hulle Chest 2016
Cancer Associated DVT Of Leg or PE van der Hulle Chest 2016
Cancer Associated DVT Of Leg or PE van der Hulle Chest 2016
Cancer Associated Upper Extremity DVT The guidance statement from the International Society of Thrombosis and Haemostasis recommends treating for at least 3 months and then continue until the cancer is in remission They acknowledge that this recommendation is extrapolated from those for lower extremity DVT ASCO says duration is unclear 3 to 6 months seems reasonable It is possible (even likely) that the duration can be shorter if the catheter has been removed. NCCN recommends at least 3 months or as long as the catheter is in place Debourdeau JTH 2013 Schiffer J Clin Onc 2013 NCCN Guidelines 2016
5-year rate of recurrence 30% composite
Duration of Therapy First Unprovoked Proximal or Distal DVT Of Leg or PE Treatment with anticoagulation for 3 months is recommended over treatment of a shorter period With low to moderate bleeding risk, extended (no stop date) therapy is suggested With high bleeding risk, 3 months is suggested Kearon Chest 2016
Periodic Assessment For all patients who receive extended anticoagulant therapy, the continued treatment should be reassessed periodically Usually done annually, but should be done any time the patient s condition changes Kearon Chest 2012
Bleeding Risks Risk Factors Age > 65 years Thrombocytopenia Renal Failure Frequent Falls Age > 75 years Previous Stroke Liver Failure Alcohol Abuse Previous bleeding Diabetes Poor Anticoag Control Cancer Anemia Comorbidity & Reduced Functional Capacity Metastatic Cancer Antiplatelet Therapy Recent Surgery Categorization of Risk of Bleeding Estimated Absolute Risk of Major Bleeding, % Low Risk (0 Risk Factors) Moderate Risk (1 Risk Factor) High Risk (2 or more Risk Factors) Anticoagulation 0-3 months Baseline Risk (%) 0.6 1.2 4.8 Increased Risk (%) 1.0 2.0 8 Total Risk (%) 1.6 3.2 12.8 Anticoagulation after 1 st 3 months Baseline Risk (%) 0.3 0.6 > 2.5 Increased Risk (%) 0.5 1.0 > 4.0 Total Risk (%) 0.8 1.6 > 6.5 Kearon Chest 2012
VTE Recurrence Risk at a Glance Estrogen women are those on estrogen therapy at the time of the clot Kearon Ann Int Med 2015
Prediction Models
Prediction Models Prandoni Throb Haemost 2014
Men Continue and HERDOO2 Rodger CMAJ 2008
Vienna Prediction Score http://cemsiis.meduniwien.ac.at/en/kb/scienceresearch/software/clinical-software/recurrent-vte
Vienna Prediction Score http://cemsiis.meduniwien.ac.at/en/kb/scienceresearch/software/clinical-software/recurrent-vte
Vienna Prediction Score
Vienna Prediction Score
DASH SCORE
Thrombophilia While thrombophilias are considered a risk factor for initial VTE, available evidence does not support the use of inherited thrombophilia testing to determine risk of recurrent VTE Correctly diagnosed antiphospholipid antibody syndrome (APS), considered an acquired thrombophilia does seem to confer a high recurrence risk Streiff J Thromb Thrombolysis 2015
Residual Vein Obstruction A systematic review of studies of RVO as a predictor of occurrence in 2011 concluded RVO is not a strong predictor of recurrence of unprovoked clots A recent randomized controlled trial by Prandoni concluded that an assessment of RVO after 3 months of therapy for an unprovoked clot can help guide treatment options They acknowledged that male sex, previous VTE, and extensive clots were better predictors of recurrence Testing for RVO might be employed in combination with other risk factors if the risk for recurrence seems unclear. Carrier JTH 2011 Prandoni Sem in Thromb Hemostasis 2015 Streiff J Thromb Thrombolysis 2015
Second Unprovoked Proximal or Distal DVT Of Leg or PE Treat with extended anticoagulation with low to moderate bleeding risk With high bleeding risk, 3 months is suggested Kearon Chest 2016 Risk of recurrence is 50% higher than the risk following a first unprovoked VTE
Duration of Therapy Aspirin for Extended Treatment In patients with an unprovoked proximal DVT or PE who are stopping anticoagulant therapy, and do not have a contraindication to aspirin, aspirin therapy is suggested to prevent recurrent VTE Kearon Chest 2012
Aspirin for Extended Treatment INSPIRE A combined patient-level analysis of the WARFASA and ASPIRE trials Enteric ASA 100mg daily vs placebo after 6-18 months (WARFASA) or 6 weeks to 2 years (Aspire) anticoagulation for unprovoked VTE Planned and protocol for this project was developed before unblinding of the results of either trial Of 1224 patients, 193 had recurrent VTE over 30.4 months median follow-up After adjustment for treatment adherence, recurrent VTE was reduced by 42% in the ASA group Similar rates of bleeding (0.4 to 0.5%) Simes Circulation 2014
CASE STUDIES
Clark Clark K. is a 28 year old man who developed an extensive proximal DVT after suffering multiple injuries falling off a building While in the hospital, Clark tested positive for protein C deficiency Due to his hypercoagulable state, the discharge summary suggests an indefinite duration of anticoagulant therapy
Clark After several months of treatment elsewhere, Clark has recently transferred to your service. He is now a 29 year old gentleman who has been on warfarin for one year due to an extensive LE DVT after multiple trauma. He was tested positive for protein C deficiency. He is requesting a home meter as monthly appointments to the clinic are difficult for him. He is always flying around to different places. What do you recommend?
Jiya Jiya is a 30 year old school teacher from Pakistan. She suffered an unprovoked PE last year. This was the only clot she has ever had. Warfarin therapy is difficult for Jiya because she enjoys practicing martial arts.
Jiya What parameters should be considered when counseling Jiya? www.burkaavenger.com
Questions?
THANK YOU!
References Ageno, W., 2015. Duration of anticoagulation after venous thromboembolism in real world clinical practice. Thrombosis Research, 135(4), pp. 666-72. Barnes, G., 2015. Venous thromboembolism: Predicting recurrence and the need for extended anticoagulation. Vascular Medicine, 20(2), pp. 143-52. Carrier, M., 2011. Residual vein obstruction to predict the risk of recurrent venous thromboembolism in patients with deep vein thrombosis: a systematic review and meta-analysis.. J Thromb Haemost, 9(6), pp. 1119-25. Clark, N., 2015. Bleeding, Recurrent Venous Thromboembolism, and Mortality Risks During Warfarin Interruption for Invasive Procedures. JAMA Internal Medicine, 175(7), pp. 1163-68. Debourdeau, P., 2013. International clinical practice guidelines for the treatment and prophylaxis of thrombosis associated with central venous catheters in patients with cancer. JTH, Volume 11, pp. 71-80. Duketis, J., 2015. Perioperative Bridging Anticoagulation in Patients with Atrial Fibrillation. NEJM, Volume 373, pp. 823-33. Garcia, D., 2013. Antiphospholipid antibodies and the risk of recurrence after a first episode of venous thromboembolism: a systematic review. Blood, 122(5), pp. 817-24. Hicks, L., 2013. The ASH Choosing Wisely campaign: five hematologic tests and treatments to question. Blood, 122(24), pp. 3879-83. Hornsby, 2014. Thrombophylia Screening. J Pharm Practice, 27(3), pp. 253-59. Kearon, C., 2012. Antithrombotic Therapy for VTE Disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest, pp. e419s- 3494S. Kearon, C., 2015. D-Dimer Testing to Select Patients With a First Unprovoked Venous Thromboembolism Who Can Stop Anticoagulant Therapy: A Cohort Study. Annals of Internal Medicine, Volume 162, pp. 27-34.
References Khorana, A., 2016. Guidance for the prevention and treatment of cancer-associated venous thromboembolism. J. Thromb Thrombolysis, Volume 41`, pp. 81-91. Linkins, L., 2012. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.. Chest, 141(2(Suppl)), pp. e495s-e530s. Lyman, G., 2015. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: American Society of Clinical Oncology Clinical Practice Guideline Update 2014. J Clin Onc, 33(6), pp. 654-656. National Comprehensive Cancer Network, 2016. NCCN Guidelines Cancer-Associated Venous Thromboembolic Disease. [Online] Available at: https://www.nccn.org/professionals/physician_gls/pdf/vte.pdf [Accessed 16 August 2016]. Prandoni, P., 2014. Optimal Duration of anticoagulation: Provoked versus unprovoked VTE and role of adjunctive thrombophilia and imaging tests. Thrombosis Haemostasis, Volume 112, pp. 1210-15. Rodger, M., 2008. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy.. J Canadian Medical Association, 179(5), pp. 417-26. Rodger, M (2016, August). HERDOO2 Rule to Guide Treatment Duration for Unprovoked Venous Thrombosis: The REVERSE II Study. Research presented at the European Society of Cardiology, Rome, Italy. Shiffer, C., 2013. Central Venous Catheter Care for the Patient with Cancer. J Clin Oncol, 31(10), pp. 1357-1370. Streiff, M., 2015. Predicting the risk of recurrent venous thromboembolism (VTE). J Thromb Thrombolysis, Volume 39, pp. 353-366. Streiff, M., 2016. Guidance for the treatment of deep vein thrombosis and pulmonary embolism. J Thromb Thrombolysis, Volume 41, pp. 32-67. Tosetto, A., 2012. Predicting disease recurrence in patients with previous unprovoked venous thromboembolism: a proposed prediction score (DASH).. J Thromb Haemost, 10(6), pp. 1019-25. van der Hulle, T., 2016. Cohort Study on the Management of Cancer-Associated Venous Thromboembolism Aimed at the Safety of Stopping Anticoagulant Therapy in Patients Cured of Cancer. Chest, 149(5), pp. 1245-1251.