Venous Thromboembolic Disease: The Role of Novel Anticoagulants Grant M. Greenberg MD, MA, MHSA

Overview Identify the challenges in diagnosis of Venous Thromboembolic Disease Diagram current protocols/pathways for evaluation and treatment of VTE Review current anticoagulation options and their benefits/trade offs

Diagnosing VTE can be tricky Diagnosis can be challenging and uncertain Risk factors are non-specific Clinical findings alone are not adequate Imaging Modalities need to be put into context of pre-study probability Labs such as D-Dimer only helpful if negative

Diagnostic Approach to VTE DVT  Presentation – No “typical” story makes dx challenging  Risk Factors – To apply pre-test probability  Testing – Imaging – Laboratory PE  Presentation – Can be used to assess pre-test probability  Risk Factors – Same as for DVT  Testing – Imaging – Laboratory

VTE Selected Risk Factors Prior VTE Advanced age (>70) Malignancies Surgery Trauma Pregnancy Hormonal agents containing estrogen Obesity Immobilization Inherited Thrombophilia CHF Polycythemia vera Nephrotic syndrome Inflammatory Bowel Disease

Wells Criteria for Likelihood Estimation of DVT

Finding a LE DVT: the challenge of the clinical scenario Calf swelling or tenderness (50% of cases) Leg Pain Palpable Cord may or may not be present Tissue Erythema Superficial Thrombophlebitis has similar S/Sx

LE DVT: Diagnostic Modalities Low Pre-test Probability Exclude dx with neg hsD-Dimer (NPV 99.5%) If D-Dimer positive, proceed with Duplex US (NPV > 99.5%) Moderate Pre-test Probability Whole leg Duplex positive, proceed to treatment High Pre-test Probability Whole leg Duplex positive, proceed to treatment

PE: Associated Clinical Findings

Modified Wells’ Criteria for Assessment of Pretest Probability for Pulmonary Embolism CriteriaPoints Clinical signs and symptoms of DVT (objectively measured calf swelling and pain with palpation in the deep vein region) 3.0 An alternative diagnosis is less likely than PE 3.0 Heart rate >100 beats per minute1.5 Immobilization or surgery in the previous four weeks 1.5 Previous DVT or PE1.5 Hemoptysis1.0 Malignancy (on treatment, treated in the past six months, or palliative care) 1.0 ScoreMean ProbabilityRisk <2 points3.6Low 2 to 6 points20.5Intermediate >6 points66.7High From Wells et al., Ann Int Med 2001;135:

PE: Diagnosis Low Clinical Likelihood hs D-Dimer, if negative, no further testing (NPV 99%) hs D-Dimer positive, proceed with imaging Intermediate or High Clinical Likelihood Direct to imaging

PE Imaging Modalities CT Angiography (Pulmonary Angiography) Requires IV Contrast CT Venography (Pelvic Venography) V/Q (Ventilation/Perfusion Scan) Still useful if no infiltrate/effusion and CTA contraindicated A positive LE Duplex US in the setting of High Clinical Likelihood can establish the diagnosis without additional imaging

Managing CTA results by pre-test probability still important… Further investigation is required if: Low clinical likelihood and CTA positive for sub- or segmental embolism a high or intermediate clinical likelihood, but negative CTA results V/Q scanning may be helpful or Pulmonary angiography may be required in some cases avoid the risk of missing PE or unnecessary long-term anticoagulation

VTE Treatment: Oral Anticoagulants ** not FDA approved for VTE as of 5/2014

Novel Oral Anticoagulants (NOACs) PRO Do not require monitoring blood work Lower bleeding risks “Non-inferior” to standard therapy Bridging with heparin (LMWH) not required CON No reversal agents yet No clear advantage for compliance $$$$$ (non-generic)

NOACs and Compliance Chatterjee S, Sardar P, Giri J, Ghoshi J, Mukherjee D. Treatment discontinuations with new oral agents for long-term anticoagulation: insights from a meta-analysis of 18 randomized trials including 101,801 patients Mayo Clinic Proceedings (July 2014): p896Mayo Clinic Proceedings

Duration of Therapy 3 monthsIndefiniteOther Calf Vein DVT w/reversible causex Idiopathic VTEx Proximal DVT, no prior event, with reversible cause x Proximal DVT or PE, no prior event, without reversible cause x VTE and active cancerx Thrombophilia: heterozygous factor V Leiden, first VTE, x recurrent VTE, +/- thrombophilia with affected first deg relatives, protein c, protein S, antiphospholipid syndrome x VTE in PregnancyxAnd for at least 6 weeks PP

Managing Anticoagulation: There’s a website for that….