Conserva)ve Treatment of PE/ DVT

Transcription

1 Conserva)ve Treatment of PE/ DVT Amir Kaki, MD FACC FSCAI Asst Prof of Medicine Wayne St SOM Medical Director Cardiac Catheteriza)on Lab Heart Hospital DMC Detroit, MI

2 Incidence Acute pulmonary embolism (PE) is a prevalent condi)on,1 affec)ng up to one out of every 1,000 to 2,000 Americans each year. ARer acute PE, mortality surpasses 15% within the first three months, 4 and up to 30% of pa)ents will die without treatment.

3 Treatment An)coagula)on remains the cornerstone of therapy. Current op)ons for advanced therapy include: fibrinolysis, catheter- assisted embolectomy, surgical embolectomy, IVC filter inser)on. The decision to select advanced therapy for submassive PE or to maintain an)coagula)on alone must be individualized because of a paucity of trials to help guide management.

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5 Standard In the absence of contraindica)ons, all pa)ents with acute PE should be an)coagulated. Unfrac)onated heparin (UFH) is the most widely used an)coagulant for the ini)al treatment of PE. Once the pa)ent has stabilized, op)ons for outpa)ent an)coagula)on include warfarin therapy, long- term enoxaparin, or a novel oral an)coagulant agent (such as dabigatran, rivaroxaban, apixaban, or edoxiban).

6 Risk Stra)fica)on Pa)ents with low- risk (or "nonmassive") PE include those without hemodynamic instability or evidence of right ventricular (RV) dysfunc)on. Consistent with the guidelines, we treat these low- risk pa)ents with an)coagula)on alone (in the absence of contraindica)ons), and otherwise manage them suppor)vely. It is generally accepted that the risks of thrombolysis outweigh the benefits in pa)ents with low- risk PE.

7 Sub- massive PE 30% of pa)ents who present with intermediate- risk (or "submassive") PE. By defini)on, these pa)ents are hemodynamically stable (i.e., systolic blood pressure [SBP] 90 mm Hg), but have other features predic)ve of adverse outcomes including either RV dysfunc)on or myocardial necrosis. As RV dysfunc)on may signify impending hemodynamic compromise, this is a par)cularly concerning finding and has been associated with worsened prognosis, including increased short- and long- term mortality up to one year arer submassive PE.

8 Intermediate Risk Given the paucity of data on how to op)mally manage pa)ents with intermediate- risk PE, prac)ce varies widely, with most clinicians favoring conserva)ve management (i.e., an)coagula)on alone) due to the perceived risks of systemic thrombolysis.

9 Fibrinolysis Fibrinolysis func)ons as a medical embolectomy and when successful will rapidly reverse hemodynamic compromise and gas exchange derangements. In pa)ents with submassivepe, fibrinolysis relieves RV pressure overload and may avert impending hemodynamic collapse and death due to progressive RV failure

10 Sub Massive PE The 2008 ACCP Guidelines include fibrinolysis as an op)on for submassive PE pa)ents who are judged to have a low risk of bleeding (Grade 2B). Pa)ents with a low risk of bleeding have normal renal func)on, are not frail, and are not receiving dual an)platelet therapy

11 MAPPET 3 The Management Strategies and Prognosis of Pulmonary Embolism Trial- 3 (MAPPET- 3) randomized 256 pa)ents with submassive PE to receive recombinant )ssue plasminogen ac)vator (t- PA) 100 mg over two hours followed by unfrac)onated heparin infusion or placebo plus heparin an)coagula)on

12 NOACs and DVT/PE

13 Apixiban Edoxaban

14 December 6, 2009

15 RECOVER N = 2564, Follow- up 6 months, double- blind Inclusion: DVT or PE with planned tx for 6 months Exclusion: Symptoms longer than 6 months, PE with HD instability or use of TPA, indica)on for warfarin, unstable heart disease, high risk of bleeding, transaminases, life expectancy < 6 months, CrCl < 30, pregnancy Randomized to 150 mg dabigatran BID vs warfarin Primary outcome: symptoma)c VTE or death 2/2 VTE

16 NIM 2.75

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18 December 2010

19 EINSTEIN- DVT N = 3449, most tx for 6 months, open- label Inclusion: DVT w/o PE Exclusion: CrCl <30, liver disease, ac)ve bleeding or high risk for bleeding, HTN, contraindica)on to an)coagula)on, or received UFH/LMWH for > 48 hrs Randomized to rivaroxaban at 15 mg BID for 3 weeks then 20 mg daily for 3, 6, or 12 months vs warfarin Primary outcome: symptoma)c recurrent VTE

20 NIM 2.0

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22 NOACs and Overall Risks

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25 RE COVER II The RE- COVER II trial found dabigatran 150 mg twice- daily to be comparable with standard treatment with similar major bleeding event rates and lower overall bleeding rates Rivaroxaban was evaluated in two studies. Must bridge with 5 days of Heparin or LMWH

26 EINSTEIN PE The EINSTEIN- PE trial14 involved a similar comparison, this )me for the treatment of acute PE. Rivaroxaban was again comparable with standard therapy in preven)ng the primary end point. Major or clinically relevant non- major bleeding rates were similar between the two groups, but there were significantly fewer major bleeds in the rivaroxabangroup. NO bridging needed

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28 AMPLIFY The AMPLIFY trial showed that apixaban (10 mg twice- daily for 1 week, then 5 mg twice- daily) demonstrated comparable efficacy to standard therapy in treatment of acute DVT and PE. Apixaban had a superior safety profile with major bleeding occurring in 0.6% of pa)ents compared with 1.8% in the conven)onal treatment group (p<0.001).

29 Hokusai VTE Edoxaban trial Non inferior to standard therapy Safety endpoint met Requires Bridging

30 Summary Non- inferior for treatment of DVT/PE Reduc)on hemorrhagic stroke rate Reduced rate of fatal bleeding events Increased incidence of GI bleeds (Pradaxa) Perhaps increased incidence of MIs with dabigatran

31 Summary We have Op)ons Pradaxa (5 days requires IV inita)on or sub q) Xarelto Eliquis (Less Bleeding) Savaysa (5 days Require IV ini)a)on or subq)