Transcatheter Aortic Valve Replacement and NOACs

Another area of interest for using NOACs is in the transcatheter aortic valve replacement (TAVR) population. This procedure was developed for those with severe aortic stenosis as an option instead of open aortic valve replacement surgery.  There is a continued need for optimal antithrombotic regimens and there is an ongoing clinical trial to evaluate this. 

Current guidelines recommend 3 to 6 months of DAPT (dual antiplatelet therapy) with aspirin plus a P2Y12 inhibitor following TAVR.  If a patient has a preexisting indication for oral anticoagulation use, such as atrial fibrillation, they should continue taking the same anticoagulant following TAVR. The rationale for this strategy is twofold. The first is to protect against device-related thromboembolic events while endothelialization of the metallic catheter valve frame is occurring.27 The second is to decrease the incidence of bioprosthetic valve thrombosis and subclinical thrombosis. Consideration should be given to the benefits vs the bleeding risk. If the bleeding risk is high, then single antiplatelet therapy would be indicated. 

Multiple clinical trials are investigating the efficacy and safety profiles of dual antiplatelet vs single antiplatelet vs oral anticoagulants in patients with TAVR. The use of oral anticoagulant therapy has been shown to prevent the development of both clinical valve thrombosis and subclinical leaflet thrombosis without increased bleeding in comparison to antiplatelet therapy. Clinical trials are presently investigating the use of apixaban, edoxaban, and rivaroxaban.28 


Continue Reading

NOAC Therapy in Oncology

Most recently, clinical trials are ongoing evaluating NOACs, particularly rivaroxaban and apixaban, for the use in thromboprophylaxis in ambulatory cancer patients and in patients with metastatic disease undergoing chemotherapy.39,30 The National Comprehensive Cancer Network (NCCN) guidelines for patients with cancer who are considered at high risk for VTE recommend thromboprophylaxis with unfractionated heparin (UFH), LMWH, or fondaparinux. Unfractionated heparin and LMWH both inactivate factor Xa by improving the action of antithrombin.30 Unfractionated heparin is predominantly metabolized by the liver but there are no significant dose adjustments. LMWH is metabolized by the kidneys so renal impairment may affect excretion and may require dosing considerations. Fondaparinux is a factor Xa inhibitor metabolized by the kidney; thus, dose adjustment may be needed for renal impairment.31 The recommendations for surgical cancer patient who are at high risk is the same.

The Khorana scoring system (Table 5) is used for ambulatory medical oncology patients to determine risk.32 For intermediate-risk patients with a score greater than or equal to 2, prophylaxis is considered using apixaban or rivaroxaban for 6 months.

Table 5. Khorana Scoring System32

Stomach  +2
Pancreas+2
Lymphoma +1
Gynecologic    +1
Bladder  +1
Testicular     +1
Lung +1
Other+0
Prechemotherapy PLT count ≥350 × 109/L+1
Hemoglobin level <10 g/L+1
Prechemotherapy leukocyte count >11 × 109/L+1
BMI >35+1
PLT, platelet
Table adapted from Mulder et al.32

Patients with multiple myeloma are risk-stratified using the SAVED or IMPEDE scoring system. The SAVED score is based on the following criteria: a history of previous surgery, Asian race, VTE history, age 80 years or older, and dexamethasone dose. The researchers found that this model stratified about 30% of patients as at high risk for VTE.33

The IMPEDE score is based on immunomodulatory agent, BMI greater than or equal to 25, pelvic or femur fracture, erythropoietin stimulating agent, dexamethasone/doxorubicin, Asian ethnicity, VTE history, tunneled catheter/central line, and existing thromboprophylaxis.34 Those with a SAVED score greater than or equal to 2 or IMPEDE score greater than or equal to 3, warfarin or LMWH are used. For patients with SAVED score less than 2 or IMPEDE score less than 3, clinician should consider apixaban or aspirin therapy.35

Specific criteria are used for patients with and without gastric/gastroesophageal lesions.31 For patients without gastric/gastroesophageal lesions, apixaban is preferred over rivaroxaban for thromboprophylaxis. For patients with gastric/gastroesophageal lesions, dalteparin is preferred over enoxaparin. Preferred combination therapy options for patients without gastric/gastroesophageal lesions include edoxaban plus LMWH/UFH or LMWH/UFH for 5 days, followed by edoxaban. If this therapy cannot be used, the dabigatran plus LMWH/UFH can be used for 5 days, followed by dabigatran.31 A third option may include warfarin plus LMWH/fondaparinux/UFH until INR reaches greater than or equal to 2.0, then continue with warfarin alone.36

Reversal of NOAC Action

With the development of NOACs, there became a concern surrounding the ability to reverse these agents in a bleeding emergency. Reversal agents have been developed for patients taking NOACs who need urgent surgery or who have life-threatening bleeding. Idarucizumab is a reversal agent for the direct thrombin inhibitor dabigatran.37 This agent is a monoclonal antibody fragment that is given intravenously as a 1-time dose.  The reversal agent for the factor Xa inhibitors (apixaban, and rivaroxaban) is coagulation factor Xa (recombinant), which is a modified human factor Xa protein given as a 1-time intravenous bolus or infusion. It is not indicated for the reversal of edoxaban.38

Conclusion

Over the past decade with the development of NOACs, numerous changes and advances have been made in treating and preventing stroke related to atrial fibrillation, DVT, and PE treatment and prophylaxis; CAD risk reduction; and thromboprophylaxis in cancer patients. Practitioners should be aware of new recommendations regarding NOACs and also the importance of proper dosing for each population. Due to the complexity of dosing based on condition, renal function, age, weight, and bleeding risk, the practitioner must be extremely vigilant to assure patient safety and appropriate dosing. As more clinical trials and data become available, the expanded use of NOAC use will continue.

Barbara Bentz, RN, MSN, CRNP, is an instructor of medicine in the Heart and Vascular Institute at Penn State Health, specializing in electrophysiology. Denise Rhodes, MSN, CRNP, FNP-BC, is an instructor of medicine in the Heart and Vascular Institute at Penn State Health, specializing in interventional cardiology and structural heart disease.

References

  1. Bentz BA. Nonvitamin K antagonist oral anticoagulants in everyday practice: Stroke prevention in atrial fibrillation and treatment of venous thromboembolism. J Am Assoc Nurse Pract. 2015;27(12):721-731. doi:10.1002/2327-6924.12330
  2. Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-51. doi:10.1056/NEJMoa0905561
  3. Patel MR, Mahaffey KW, Garg J, et al; ROCKET AF Investigators. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365(10):883-891. doi:10.1056/NEJMoa1009638
  4. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-992. doi:10.1056/NEJMoa1107039
  5. Giugliano RP, Ruff CT, Braunwald E, et al; ENGAGE AF-TIMI 48 Investigators. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369(22):2093-104. doi:10.1056/NEJMoa1310907
  6. Brenner B, Hull R, Arya R, et al. Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in high-risk patient groups: cancer and critically ill. Thromb J. 2019;17:6. doi:10.1186/s12959-019-0196-6
  7. Rivera-Caravaca JM, Camelo-Castillo A, Ramírez-Macías I, et al. Antithrombotic therapy in patients with peripheral artery disease: a focused review on oral anticoagulation. Int J Mol Sci. 2021;22(13):7113. doi:10.3390/ijms22137113
  8. Eliquis. Prescribing information. Bristol Myers Squibb; 2021. Accessed October 7, 2021.
  9. Xarelto. Prescribing information. Janssen; 2021. Accessed October 7, 2021.
  10. Savaysa. Prescribing information. Daiichi Sankyo, Inc; 2021. Accessed October 7, 2021.
  11. Pradaxa. Prescribing information. Boehringer Ingelheim; 2021. Accessed October 7, 2021.
  12. BRIDGE Study Investigators. Bridging anticoagulation: is it needed when warfarin is interrupted around the time of a surgery or procedure? Circulation. 2012;125(12):e496-8. doi:10.1161/CIRCULATIONAHA.111.084517
  13. Lip GY. The CHA₂DS₂-VASc score for stroke risk stratification in patients with atrial fibrillation: a brief history. Eur Heart J. 2015;36(42):2880-2885. doi:10.1093/eurheartj/ehv431
  14. January CT, Wann LS, Calkins H, et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019;74(1):104-132. doi:10.1016/j.jacc.2019.01.011
  15. Balla SR, Cyr DD, Lokhnygina Y, et al. Relation of risk of stroke in patients with atrial fibrillation to body mass index (from Patients Treated With Rivaroxaban and Warfarin in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation Trial). Am J Cardiol. 2017;119(12):1989-1996. doi:10.1016/j.amjcard.2017.03.028.
  16. Narouze S, Benzon HT, Provenzano D, Buvanendran A, De Andres J, Deer T, Rauck R, Huntoon MA. Interventional spine and pain procedures in patients on antiplatelet and anticoagulant medications (Second Edition): Guidelines From the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain. Reg Anesth Pain Med. 2018;43(3):225-262. doi:10.1097/AAP.0000000000000700
  17. Dawwas GK, Brown J, Dietrich E, Park H. Effectiveness and safety of apixaban versus rivaroxaban for prevention of recurrent venous thromboembolism and adverse bleeding events in patients with venous thromboembolism: a retrospective population-based cohort analysis. Lancet Haematol. 2019;6(1):e20-e28. doi:10.1016/S2352-3026(18)30191-1
  18. Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, Mebazaa A, Merli G, Schellong S, Spyropoulos AC, Tapson V; MAGELLAN Investigators. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013;368(6):513-23. doi:10.1056/NEJMoa1111096.
  19. Spyropoulos AC, Lipardi C, Xu J, et al. Improved benefit risk profile of rivaroxaban in a subpopulation of the MAGELLAN Study. Clin Appl Thromb Hemost. 2019;25:1076029619886022. doi:10.1177/1076029619886022
  20. Mega JL, Braunwald E, Wiviott SD, et al; ATLAS ACS 2–TIMI 51 Investigators. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366(1):9-19. doi:10.1056/NEJMoa1112277
  21. Floyd CN. Dual antiplatelet therapy in coronary artery disease: comparison between ACC/AHA 2016 and ESC 2017 Guidelines. Eur Cardiol. 2020;15:1-3. doi:10.15420/ecr.2019.09
  22. Alexander JH, Lopes RD, James S, et al; APPRAISE-2 Investigators. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011;365(8):699-708. doi:10.1056/NEJMoa1105819
  23. Gibson WJ, Gibson CM, Yee MK, et al. Safety and efficacy of rivaroxaban when added to aspirin monotherapy among stabilized post‐acute coronary syndrome patients: a pooled analysis study of ATLAS ACS‐TIMI 46 and ATLAS ACS 2‐TIMI 51. J Am Heart Assoc. 2019;8(5):e009451.
  24. Eikelboom JW, Connolly SJ, Bosch J, et al; COMPASS Investigators. Rivaroxaban with or without aspirin in stable cardiovascular disease. N Engl J Med. 2017;377(14):1319-1330. doi:10.1056/NEJMoa1709118
  25. Anand SS, Eikelboom JW, Dyal L, et al; COMPASS Trial Investigators. Rivaroxaban plus aspirin versus aspirin in relation to vascular risk in the COMPASS Trial. J Am Coll Cardiol. 2019;73(25):3271-3280. doi:10.1016/j.jacc.2019.02.079
  26. Cho SW, Franchi F, Angiolillo DJ. Role of oral anticoagulant therapy for secondary prevention in patients with stable atherothrombotic disease manifestations. Ther Adv Hematol. 2019 Jul 12;10:2040620719861475. doi:10.1177/2040620719861475
  27. Guedeney P, Mehran R, Collet JP, Claessen BE, Ten Berg J, Dangas GD. Antithrombotic therapy after transcatheter aortic valve replacement. Circ Cardiovasc Interv. 2019;12(1):e007411. doi:10.1161/CIRCINTERVENTIONS.118.007411
  28. Rosseel L, De Backer O, Søndergaard L. Clinical valve thrombosis and subclinical leaflet thrombosis following transcatheter aortic valve replacement: is there a need for a patient-tailored antithrombotic therapy? Front Cardiovasc Med. 2019;6:44. doi:10.3389/fcvm.2019.00044
  29. Prins MH, Lensing AW, Brighton TA, et al. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN-DVT and EINSTEIN-PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematol. 2014;1(1):e37-46. doi:10.1016/S2352-3026(14)70018-3.
  30. Streiff MB, Holmstrom B, Angelini D, et al. NCCN Guidelines insights: cancer-associated venous thromboembolic disease, Version 2.2018. J Natl Compr Canc Netw. 2018;16(11):1289-1303.
  31. Arixtra. Prescribing information. GlaxoSmithKline; 2009. Accessed October 8, 2021.
  32. Mulder FI, Candeloro M, Kamphuisen PW, et al; CAT-prediction collaborators. The Khorana score for prediction of venous thromboembolism in cancer patients: a systematic review and meta-analysis. Haematologica. 2019;104(6):1277-1287. doi:10.3324/haematol.2018.209114
  33. Li A, Wu Q, Luo S, et al. Derivation and validation of a risk assessment model for immunomodulatory drug-associated thrombosis among patients with multiple myeloma. J Natl Compr Canc Netw. 2019;17(7):840-847. doi:10.6004/jnccn.2018.7273
  34. Sanfilippo KM, Luo S, Wang TF, et al. Predicting venous thromboembolism in multiple myeloma: development and validation of the IMPEDE VTE score. Am J Hematol. 2019;94(11):1176-1184. doi:10.1002/ajh.25603
  35. Ladha D, Mallick R, Wang TF, Caiano L, Wells PS, Carrier M. Efficacy and safety of apixaban for primary prevention in gastrointestinal cancers: A post-hoc analysis of the AVERT trial. Thromb Res. 2021;202:151-154. doi:10.1016/j.thromres.2021.03.013
  36. Agnelli G, Becattini C, Meyer G, et al; Caravaggio Investigators. Apixaban for the treatment of venous thromboembolism associated with cancer. N Engl J Med. 2020;382(17):1599-1607. doi:10.1056/NEJMoa1915103.
  37. Praxabind. Prescribing information. Boehringer Ingelheim; 2015. Accessed October 8, 2021.
  38. Andexx. Prescribing information. Portola Pharmaceuticals, Inc; 2021. Accessed October 8, 2021.

This article originally appeared on Clinical Advisor