Mark H. Meissner, MD Peter Gloviczki Professor of Venous & Lymphatic Disorders University of Washington School of Medicine

Transcription

1 Pulmonary Embolism Response Teams Not So Fast Early Interventions is a House of Cards Mark H. Meissner, MD Peter Gloviczki Professor of Venous & Lymphatic Disorders University of Washington School of Medicine

2 Disclosures Mark H. Meissner, MD I Have No Disclosures Relevant To This Presentation

3 PE Associated Mortality ACCP Guidelines, Chest % if cardiopulmonary arrest occurs (1% of pts) 30% if hypotension develops (5% of patients) 2 5% without hypotension Although the risk of dying of PE differs markedly among patients, no validated risk prediction tool is available.

4 PE Risk Stratification Jaff M, AHA Guidelines, Circulation 2011 Massive PE Submassive PE Minor / Non- Massive PE High risk Moderate risk Low risk 30% mortality 2 5% mortality Systemic lytics??? Anticoagulation Sustained hypotension Ionotropic support Persistent bradycardia ( 40) Pulselessness Normotensive (SBP 90) Myocardial injury Troponin I >0.4 ng/ml Troponin T >0.1 ng/ml BNP > 90 pg/ml RV dysfunction Normotensive (SBP 90) No myocardial injury No RV dysfunction

5 The argument for lytic therapy in submassive PE is entirely based on the association of impaired RV function with mortality This argument IS a HOUSE OF CARDS RV dyfunction may be statistically associated with BUT IT IS NOT a surrogate marker for mortality

6 950 patients with PE Echocardiography on admission 3.3% mortality AND RV/LV ratio > % Positive Predictive Value = 6% Negative Predictive Value = 98% (i.e VERY few die) RV/LV ratio < % RV/LV ratio > 0.9 as a predictor of death This is NOT a surrogate for mortality AND Is NOT a valid endpoint for trials Sensitivity 72% Specificity 58%

7 And Randomized Trials Show No Benefit The PEITHO Study, ACC patients with confirmed acute PE No hemodynamic collapse RV dysfunction AND myocardial injury Randomized to Hardly a positive trial Weight adjusted tenecteplase bolus + UFH Placebo + UFH No mortality benefit NNT (hypotension) 29 NNH (stroke) 45

8 What About Catheter-Directed Lysis? Potential For More rapid lysis More complete lysis Lower lytic doses Fewer bleeding complications And Ultrasound Accelerated Thrombolysis Much higher costs

9 And It Does Seem To Improve RV Function Kennedy RJ, J Vasc Intervent Radiol patients with massive / submassive PE Ekos U/S accelerated thrombolysis t-pa at 1 mg / hr 100% technical success Mean t-pa dose mg Mean infusion time hrs 98% with > 50% lyis Mean PA pressure reduced 27 ( 9) to 20 ( 6) mm Hg 93% 90 day survival

10 The ULTIMA Trial Kucher N, Circulation patients with RV / LV ratio > 1 randomized Unfractionated heparin (UFH) UFH + U/S accelerated lysis X 15 hours (10 or 20 mg t-pa) Complications 1 death in UFH group (pancreatic cancer) No major bleeding events Maybe fewer complications 4 minor bleeding Perhaps appropriate events in highly selected patients UFH 1 But U/S accelerated lysis 3 (10%) Still no demonstrated mortality or long-term benefit RV/LV Ratio (mean SD) Lysis UFH p Baseline hrs < days

11 And Make No Mistake This IS Industry Driven

12 Does this Technology Have Benefits? Engelberger RP, Circ Cardiovasc Interv patients with I-F DVT < 2 weeks duration randomized 15 hours (20 mg t-pa) ultrasound-assisted CDT 15 hours (20 mg t-pa) CDT (U/S not activated) Outcome Ultrasound-Assisted CDT Alone p CDT (n = 24) (n = 24) % Thrombus Reduction 55 ( 27) % 54 ( 27) %.91 Adjunctive PMT / CDT 7 (29%) 11 (46%).37 Adjunctive Stenting 19 (80%) 20 (83%).99 Major Bleeding 1 (4.2%) 0.99 Hospitalization 2.7 ( 1.4) days 2.8 ( 1.3) days.83 Villalta 3 months 3.0 ( 3.9) 1.9 ( 1.9).21

13 Might There Be A Late Benefit? Chow V, Resp Med pts followed 7.7 ( 1.4) yrs after PE 6 minute walk test 448 ( 114) m versus predicted 475 ( 89) m 10 (9.6%) with dyspnea (Borg score > 5) during walk Echocardiography RV dilation 7% Increased PASP 23% Increased PVR 21% BUT Many confounders Adequacy of initial anticoagulation Recurrent PE (24%) Clinical relevance of findings And any benefit of lysis can not be extrapolated

14 Randomized Trials Show No Late Benefit Konstantinides SV, JACC ( ) month follow-up of PIETHO trial Weight-based tenecteplase 359 patients Unfractionated heparin 350 patients 50.0 % 45.0 % 40.0 % 35.0 % 30.0 % 25.0 % 20.0 % 15.0 % 10.0 % 5.0% 0.0% 44.1% 36.6% 36.0% 30.1% 12.0% 10.9% Ab norm al Echo Exerti onal Dysp nea Class III/IV CH F Tenectep las e UF H * RV dysfunction or pulmonary hypertension

15 Conclusions Percutanteous Management of Submassive PE Trials of interventional therapy for PE must demonstrate Mortality benefit (and mortality is low for submassive PE) Improved QoL (and most patient don t have long-term impairment) RV dysfunction / injury is a statistical association NOT a surrogate for mortality The available data suggests NO mortality benefit and perhaps even increased complications from this treatment The available evidence contradicts the marketing hype

16 And Are There Benefits of This Techology? Baker R, J Vasc Interv Radiol 2012 Retrospective comparison of lysis for iliofemoral DVT Catheter-directed thrombolysis (CDT, n = 19) Ultrasound-assisted thrombolysis (UAT, n = 64) Lytic Dose rtpa (mg) Urokinase (1 X 10 6 U) Tenecteplase (mg) All (n = 83) CDT (n = 19) UAT (n = 64) p 12 ( ) 1.8 ( ) 8 (6 11) ( ) (8 18) 1.7 ( ) 8 (6 11) Infusion time 26 (21 41)25 25 (22 39) 27 (21 27).39 Percent lysis 71% (46 91) 78% (50 100) 71% (40 89).27 Major bleeding 7% (8.4) 2% (10.5) 5% (7.8).71

17 But Not Clinical Outcome George B, Vascular Medicine pts with massive / submassive PE evaluated Pre-catheter directed lysis era ( ,n = 102) Catheter directed lysis era ( , n 119) Ultrasound assisted thrombolysis (n = 32) Medical treatment (n = 87) Composite outcome Death, stoke, bleeding & recurrent PE Pre CDT era 14.7 % CDT era 21.0 % p =.23 CDT specifically associated with Increased composite outcome (23.0 vs 15.6%, p =.38) 190% ( %) increase in ICU stay 53.7% ( %) increase in hospital stay }