1 / 35

Rapid Clinical Updates: AF and VTE Guidelines Summary

Gain insights into new AF and VTE guidelines, treatment approaches, and clinical trials for managing cardiovascular risks. Stay informed on treatment duration, risk balancing, and recent recommendations.

sgonzales
Download Presentation

Rapid Clinical Updates: AF and VTE Guidelines Summary

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. www.epccs.eu Rapid Clinical updates since last EPCCS, Part 2 What’s new in AF and VTE guidelines? Prof David Fitzmaurice Birmingham, United Kingdom

  2. Declarations I have received honoraria from BI, Roche Diagnostics, Bayer, BMS-Pfizer I went to the same primary school as Matt Fay

  3. VTE Comprises DVT and PE 3rd leading cause of cardiovascular mortality 1 million deaths per year in Europe At least 50% due to hospital admission VTE causes more deaths than MRSA, AIDS, Breast Cancer and RTAs combined 1/20 lifetime incidence

  4. Aims of treatment • To prevent extension • To prevent embolisation • To allow stabilisation and recanalisation • To prevent recurrence • To prevent long term effects (PTS, PH)

  5. Current Treatment • Initial treatment with UFH, LMWH, SP • No placebo controlled trials • Minimum 5 days (average 7) • LMWH drug of choice for cancer patients

  6. Current Treatment • Combined with warfarin (VKA) • Treatment phase 3-12 months • One placebo controlled trial (PE pts, Barritt and Jordan 1960) • Duration of therapy?

  7. Current Treatment – What’s the problem? • INR monitoring • Which LMWH – HIT?? • Bleeding versus recurrence • Duration of therapy

  8. Rivaroxaban EINSTEIN phase III: study designs EINSTEIN Extension1 (superiority study) Treatment period of 6 or 12 months Confirmed symptomatic DVT or PE completing 6 or 12 months of rivaroxaban or VKA N=1,197 Rivaroxaban 20 mg od 30-day observation after treatment cessation R Placebo Day 1 EINSTEIN DVT1 and EINSTEIN PE2 (non-inferiority studies) Treatment period of 3, 6 or 12 months Confirmed acute symptomatic DVT without symptomatic PE Rivaroxaban Rivaroxaban N=3,449 15 mg bid 20 mg od 30-day observation after treatment cessation R Enoxaparin 1.0 mg/kg bid for at least 5 days, followed by VKA to start ≤48 hours, target INR range 2.0–3.0 Confirmed acute symptomatic PE with or without symptomatic DVT N=4,833 Day 1 Day 21 The EINSTEIN investigators, 1. N Eng J Med 2010;363:2499-2510 & 2. N Eng J Med 2012;366:1287-1297 L.GB.01.2013.1379 Jan 2013

  9. Einstein - Conclusion Rivaroxaban • Non-inferior acutely compared with standard therapy • Superior in terms of secondary prevention compared with placebo but some excess bleeding • Pre-specified joint analysis suggest superiority of rivaroxaban

  10. Einstein A new era?

  11. Length of Treatment • 1st episode of idiopathic VTE should be treated with warfarin at an INR of 2.0 to 3.0 at least three months • the optimal length of time and optimal degree of anticoagulation are not known • BaglinTet al. JTH 2012 Duration of anticoagulant therapy after a first episode of unprovoked pulmonary embolus or deep vein thrombosis: guidance from the scientific and standardization committee of the international society on thrombosis and haemostasis. • BoutitieFet al. BMJ 2011; 342:d3036 Influence of preceding length of anticoagulant treatment and initial presentation of venous thromboembolism on risk of recurrence after stopping treatment: analysis of individual participants' data from seven trials.

  12. Length of Treatment – balance of risksThrombosis vs bleeding • Risk benefit analysis • Patients values and preferences in regard to such risks and benefits • The potential benefit of extending anticoagulation to six (or more) months may be offset by a higher risk of bleeding and the greater cost and inconvenience of the longer duration of treatment

  13. 2012 ACCP Guidelines Recommendations based upon the perceived balance between • the number of deaths from recurrent VTE prevented by continued anticoagulation versus • the number of fatal bleeding episodes associated with continued anticoagulation

  14. Risk of rVTE after discontinuation of anticoagulation

  15. Risk of major bleeding if anticoagulation is continued

  16. BLEEDING • Warfarin in top 10 drugs largest number of serious adverse event reports submitted to the United FDA • Anticoagulants also ranked first in 2003 and 2004 in the number of total mentions of death for drugs "causing adverse effects in therapeutic use" • a common cause of emergency department visits • "black box" warning re warfarin's bleeding risk • Related to the degree of anticoagulation as well as the presence in the patient of pre-existing risk factors for bleeding.

  17. ISTH guidance 2012 • 1st provoked episode VTE or unprovoked calf DVT – a/c no greater than 3 months • 1stunprovoked episode VTE – initial treatment 3-6 months • Continue provided perceived risk a/c related bleeding not so high to preclude continued treatment

  18. ISTH guidance 2012 – unprovoked VTE • In favour of long term a/c (>3-6 months) • Male • Moderate to severe PTS • Ongoing dyspnoea • Satisfactory a/c control • Elevated D-dimer 3-4 weeks after stopping (using study validated assay)

  19. ISTH guidance 2012 – unprovoked VTE • In favour of stopping a/c at 3-6 months • female • Absent or mild PTS • Unsatisfactory a/c control • Low D-dimer 3-4 weeks after stopping (using study validated assay)

  20. Issues to consider • Patient information and counselling • Estimated risk of recurrence • Bleeding risk • Patient values and preferences Age, comorbidities, quality of life issues

  21. Length of Treatment Who is truly low risk of recurrence? Who is truly high risk of bleeding?

  22. Aspirin • Warfasa and Aspire trials • 40% reduction compared to placebo following standard treatment

  23. VTE Conclusion • New agents now available • Optimal length of time of anticoagulation are not known (low risk of recurrence) • Cost? • New care pathways • Warfarin here for a while yet

  24. AF • Most common heart rhythm disorder • 25% risk of AF for those over 40 • 5-fold increase in risk of stroke with non-valvular AF • Worsens stroke outcomes • 15% of all strokes caused by AF

  25. AF • 3 new agents • All good • All reduce ICH • Headline data • Issues: cost, monitoring, reversal

  26. New anticoagulants (1) • Dabigatran RE-LY trial NEJM 2009; 361:1139 • 150mg v warfarin • stroke: 1.0% vs 1.6%, RR 0.64 (0.51-0.81) • death: 3.6% v 4.1%, RR 0.88 (0.77-1.00) • major bleed: 3.3% v 3.6%, RR 0.93 (0.81-1.07) • 110mg v warfarin • stroke: 1.4% vs 1.6%, RR 0.92 (0.74-1.13) • death: 3.7% v 4.1%, RR 0.91 (0.80-1.03) • major bleed: 2.9% vs 3.6%, RR 0.80 (0.70-0.93)

  27. New anticoagulants (2) • Rivaroxaban ROCKET-AF NEJM 2011 • stroke 2.1% vs 2.4%, RR 0.88 (0.75-1.03) • death 1.9% vs 2.2%, RR 0.85 (0.70-1.02) on treatment • major bleeding 3.6% vs 3.4%, RR 1.04 (0.9-1.2) on treatment

  28. New anticoagulants (3) • Apixaban: ARISTOTLE NEJM 2011 • stroke 1.3% vs 1.6%, RR 0.79 (0.66-0.95) • death 3.5% vs 3.9%, RR 0.89 (0.80-0.99) • major bleeding 2.1% vs 3.1%, RR 0.69 (0.6-0.8) on treatment

  29. Who to anticoagulate? • NICE dabigatran guidance (March 2012) • Previous stroke or TIA • Age 75 or over • Left ventricular ejection fraction < 40% • Age 65 or over with a risk factor (diabetes; CHD; hypertension) • Who not to anticoagulate? • Age under 65 (unless 2 risk factors) • Age 65-74? • Role of aspirin (ESC guidelines)

  30. Stroke risk stratification CHADS2 CHA2DS2VASc2 Low risk = 0 Moderate risk = 1 High risk ≥ 2

  31. Guidelines for antithrombotic therapy in AF NICE guidelines (2006) European Society of Cardiology (2010)

  32. HAS-BLED Score for bleeding risk on oral anticoagulation in AF Feature Score if present Hypertension (systolic > 160mmHg 1 Abnormal renal function 1 Abnormal liver function 1 Age > 65 years 1 Stroke in past 1 Bleeding 1 Labile INRs 1 Taking other drugs as well 1 Alcohol intake at same time 1 Increased 1-year bleed risk with score of 3 or more on anticoagulant. Is this sufficient to justify caution or more regular review?

  33. Conclusions • New agents • More emphasis on risk:benefit • Individual versus population • Warfarin?

More Related