Pulmonary Embolism Treatment in Cancer - Is It Different 34th Brazilian Thoracic Conference 6th ALAT Congress 5th Brazil-Portugal Congress Brazilia/DF.

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  • Pulmonary Embolism Treatment in Cancer - Is It Different 34th Brazilian Thoracic Conference 6th ALAT Congress 5th Brazil-Portugal Congress Brazilia/DF November 22, 2008

    Alvin V. Thomas, Jr., M.D., FACP, FCCP Immediate Past President ACCP Howard University

  • DisclosuresI have no conflicts of interest

    Alvin V. Thomas, Jr., M.D., FCCP

  • Epidemiology of VTE in the CommunityActive cancer accounts for almost 20% of incident VTE in the communityRisk for VTE higher for patients withPancreatic cancer, lymphoma, malignant brain tumors, liver cancer, leukemia, colorectal and other digestive cancers Heit JA. Arterioscler Thromb Vasc Biol 2008;28:370-372

  • VTE and CancerPatients with idiopathic or unprovoked PE subsequently develop a cancer in 10% of cases over 5 years of follow-upRisk of thrombosis in cancer patients is 4 times higher than the general populationRisk increases 6.7 fold in patients on chemotherapyCancer patients with VTE are more likely to developRecurrent VTEMajor bleeding during anticoagulant RxRisk correlates with the extent of CA Guidelines on Dx & Rx of Acute PE. Task Force European Society of CardiologyEuropean Heart J 2008;29:2276-2315

  • Natural Course of Hemodynamically Stable PE(prospective study of 673 consecutive patients with PE)Risk factors for clinically relevant and major bleeding in patients with PE (multivariate analysis)Hospitalization, p = 0.05, OR 2.63 (1.02-6.77)Surgery, p = 0.23, OR 1.92 (0.66-5.59)COPD, p = 0.02, OR 3.89 (1.22-12.4)Malignancy, p = 0.02, OR 3.04 (1.16-7.97)Nijkeuter M et al. Chest 2007;131:517-523

  • Incidence VTE in Patients Hospitalized With Cancer(National Hospital Discharge Survey 1979-1999)19 malignancies studiedIncidence in patients with Ca - 2%Incidence in patients w/o Ca - 1% Highest incidence - pancreatic Ca - 4.3%Lowest incidences - Ca of bladder, lip, oral cavity or pharynx Overall incidence of VTE twice the rates in non cancer patientsIncidences not age dependentIncidence VTE in patients with Ca began increase in late 1980s Stein PD et al. Am J Med 2006;119:60-68

  • VTE Affects CancerMay delay planned chemotherapyNegative impact on patients quality of lifeConsumes considerable health care resourcesAccounts for nearly 10% of cancer deaths

    Khorana AA et al. J Thromb Haemost 2007;5(3): 632-634

  • VTE Affects CancerCancer patients with VTE have 2-fold or greater increase in mortality compared to patients without VTE (even when adjusting for stage) Therefore is poor prognosis for patients with cancer-associated thrombosisClose association between activation of coagulation and aggressive tumor biology Therefore the natural history and malignant nature of VTE in cancer requires aggressive prevention and therapy Lee AYY. J Thromb Thrombolysis 2008; 25:33-36

  • VTE & Cancer - AnticoagulantsAnticoagulants are usually efficacious for Rx VTE and have acceptable safety profile in most patientsCompared to patients without cancer, cancer patients have2-fold risk of recurrent VTE3-fold risk of anticoagulant-related bleedingLee AYY, Levine MN. Circulation 2003;107(23Suppl1): 117-121

  • Anticoagulation For The Initial Treatment of VTE in Patients With Cancer Compared relative efficacy and safety of LMWH & UFH between patients with and without cancerCochrane methodology for systematic reviews8 randomized control trials were studiedAkl EA et al. Cancer 2008;113:1685-1694

  • Anticoagulation For The Initial Treatment of VTE in Patients With Cancer - Results LMWH reduced mortality significantly compared to UFH in patients with cancerRR 0.71; 95%CI, 0.52-0.92 (moderate quality evidence)No reduced mortality in patients with no CaRR 0.97; 95%CI, 0.65-1.46 (low quality evidence)Difference in RR for the 2 subgroups not significant (p = 0.113)

    Akl EA et al. Cancer 2008;113:1685-1694

  • Anticoagulation For The Initial Treatment of VTE in Patients With Cancer LMWH vs UFH effect on recurrent VTEDifference not significant inCa subgroup - RR 0.78; 95% CI 0.29-2.08 (low quality evidence)Subgroup without Ca - RR 0.94; 95%CI, 0.60-1.46Or between the 2 subgroups (p = 0.367)No data on bleeding outcomes, thrombocytopenia or postphlebitic syndrome

    Akl EA et al. Cancer 2008;113:1685-1694

  • Anticoagulation For The Initial Treatment of VTE in Patients With Cancer ConclusionCurrent results suggest that LMWH is most likely superior to UFH in reducing mortality in the initial Rx of VTE for patients with cancerNeed for more and better designed trials to confirm the findings Akl EA et al. Cancer 2008;113:1685-1694

  • Recurrent VTE & Bleeding Complications in Patients with Cancer & Venous ThrombosisProspective cohort study of 12-month cumulative incidence of recurrent VTE & major bleeding from anticoagulantsIncidence recurrent VTECancer patients - 20.7%%Non cancer patients - 6.8%HR 3.2, 95% CI 1.9-5.4Major bleeding Cancer patients - 12.4%Non cancer patients - 4.9%HR 2.2, 95% CI, 1.2-4.1Prandoni P et al. Blood 2002;100(10): 3484-3488

  • VTE & Cancer Long-termTherapy676 cancer patients with acute DVT or PE were randomized to6 month course of traditional dalteparin therapy, followed by warfarinOr dalteparin alone (6 months)Dalteparin dose reduced by 20-25% after the first month of Rx (to reduce the risk of bleeding) Lee AYY. J Thromb Thrombolysis 2008; 25:33-36

  • Kaplan-Meier Estimates of the Probability of Symptomatic Recurrent Venous Thromboembolism among Patients with Cancer, According to Whether They Received Secondary Prophylaxis with Dalteparin or Oral Anticoagulant Therapy for Acute Venous ThromboembolismLee, A. et al. N Engl J Med 2003;349:146-153

  • VTE & Cancer Long-termTherapyTherefore after 6 months Rx the long-term dalteparin group experienced a 52% reduction in symptomatic recurrent VTE compared to the group on continuing warfarinEquivalent to preventing 1 episode of VTE for every 13 patients studiedNo significant difference in bleeding or in overall mortality

    Lee AYY. J Thromb Thrombolysis 2008; 25:33-36

  • VTE and Cancer - Treatment RecommendationsFor patients with PE (as well as DVT) and CancerLMWH for the first 3 to 6 months of long-term anticoagulant therapy (Grade1A)Subsequent anticoagulant therapy with VKA or LMWH indefinitely or until the cancer is resolved (Grade 1C)The risk-benefit ratio of continuing such treatment should be reassessed in the individual patient at periodic intervals (Grade 1C)

    Kearon c et al. Chest 2008;133:454S-545S

  • The End

  • VTE and Cancer - Treatment RecommendationsKearon c et al. Chest 2008;133:454S-545S

  • The End

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