The current ACCP guidelines fail clinicians and patients - Against

Transcription

1 The current ACCP guidelines fail clinicians and patients - Against Henri Bounameaux, MD Professor of Medicine Dean, Faculty of Medicine, University of Geneva Director, Division of Angiology and Hemostasis University Hospitals of Geneva Geneva, Switzerland 19th International Symposium on Thrombosis London 13 October 2012

2 «La critique est aisée mais l art est difficile» Polybe : HISTOIRE, Livre XII, C XI, 25c, 5, about 200 bc Cited by Philippe Destouches, in «Le Glorieux», II, 5, 1732 Criticizing is easy, it s doing that s difficult

3 Disclosures for Henri Bounameaux, MD In compliance with ACCME policy, this course requires the following disclosures to the session audience: Research Support/P.I. Employee Consultant Major Stockholder Speakers Bureau Honoraria Scientific Advisory Board Bayer-Schering Pharma, Schering-Plough, Daiichi-Sankyo, Swiss National Foundation No relevant conflicts of interest to declare No relevant conflicts of interest to declare No relevant conflicts of interest to declare No relevant conflicts of interest to declare Bayer-Schering Pharma, Pfizer, sanofi-aventis, GlaxoSmithKline, Daiichi-Sankyo Bayer-Schering Pharma, Pfizer, Boehringer- Ingelheim, Canon Pharma, Daïchi-Sankyo, sanofiaventis Presentation includes discussion of the following off-label use of a drug or medical device: <N/A>

4 Additional disclosure I am a panelist of AT9 and a co-author of the chapter on treatment of VTE This is an intellectual not a financial COI. Even more, it is a primary intellectual COI that would prevent me from voting on recommendations in the ACCP guidelines

5 About the ACCP guidelines Widely considered the gold standard for thrombosis prevention and therapy: Since 1986 every few years, authoritative reviews AT9 consists of 24 articles and 801 pages and 600 recommendations AT8 consisted of 22 articles and 968 pages Electronically freely accessible Dealing with oral and parenteral anticoagulants and antiplatelet drugs, prevention and treatment of VTE, perioperative management of antithrombotic therapy, and antithrombotic therapies for cardiovascular diseases

6 What is different in AT9 compared to the previous editions? New features include: Dealing explicitely with conflicts of interest Introducing evidence profiles and summaries Re-evaluating the evidence based on patient-important outcomes Expliciting more objectively values and preferences Including a front-line clinician in each panel Including a resource use consultant in each panel to address economic efficiency issues Consistent use of outcomes (e.g. bleeding) across chapters Including a chapter on DVT diagnosis Transiting to a yearly electronic update

7 Dealing with COI Financial COI Intellectual COI Primary leadership and responsibility for each article not to a thrombosis expert but to a methodologist (clinician) w/o COI Intellectual COI (primary): authorship of original studies and peer-reviewed grant funding directly bearing on a recommendation Conflicted experts can engage in discussion and draft evidence summaries but are excluded from the final decision

8 Introducing evidence profiles/summaries Evidence profiles Evidence summaries Standardized, rigorous presentation across chapters Evidence profiles summarize the quality of a body of evidence for each relevant outcome, including risk of bias, precision, consistency, directness, and publication bias Summary of evidence (in tables) to enable a standardized way of grading quality of evidence and grade of recommendation

9 Strong and weak recommendations Strong (Grade 1) recommendations apply to most patients Weak (Grade 2) recommendations (= suggestions) are sensitive to differences among patients, including their preferences

10 Re-evaluating the evidence Based on patient-important outcomes AT1-8 failed to recognize the implications of a surrogate such as screening-detected DVT, which creates major problems in making the trade-off between patient-important outcomes in the setting of thromboprophylaxis AT9 decided that symptomatic events are patient-important Accordingly, AT9 panelists concluded that the PEP trial provides moderate-quality evidence supporting the use of aspirin in major orthopedic surgery (1B), and that low-quality evidence supports a weak recommendation of LMWH over aspirin in this indication (2C)

11 Aspirin for thromboprophylaxis AT8 1A against use of aspirin as the sole agent for thromboprophylaxis in surgical patients PEP trial Multicenter, double-blind, trial comparing 160 mg vs. placebo N=17,444 patients predominantly HFS and THA Independent blinded adjudication committee, objectively confirmed end points, near-complete follow-up (99.6%) 28% (4%-47%) RRR in symptomatic DVT 19 VTE associated deaths (aspirin arm) vs. 45 (placebo) SoE: aspirin given before MOS and continued for 35 d results in 7 fewer symptomatic VTEs per 1,000 with 3 more major bleeds

12 Why patient-relevant outcomes: An example of inappropriate surrogate endpoint Combining endpoints may sometimes be tricky or even misleading P< % 10.2% Therapeutic escalation 3.4% 2.2% HEP+ALT HEP+PLA N Death Treatment of submassive PE Konstantinides S, et al. N Engl J Med. 2002;347:

13 9 th ACCP Guidelines (2012) Guidelines fail clinicians? (I) New antithrombotics Management of AC Outcome measurement Prevention (nonsurgical) Prevention (nonorthop) Prevention (orthopedics) Values and preferences Parenteral AC Perioperative AC Diagnosis of DVT Therapy of VTE Oral AC HIT AC for atrial fibrillation AC for valvular disease Ischemic stroke I and II cardiovasc prev Peripheral artery disease Medical patients Thrombophilia, pregnancy Neonates and children Antiplatelet drugstravel

14 9 th ACCP Guidelines (2012) Guidelines fail clinicians? (II) Innovations in AT9 resulted in many weak recommendations replacing the strong recommendations in AT8 AT9 had a more critical look at the evidence and the resulting inferences that some evidence is lower quality than previously believed In some controversial recommendations that were submitted to a formal vote, the endorsement by >80% of authorized panelists was deemed necessary to make a strong recommendation Conflicted experts (who often hold strong opinions) were excluded from final decisions This situation may induce some frustration

15 9 th ACCP Guidelines (2012) Guidelines fail clinicians? (III) AT9 proposed guidance in many controversial situations Aspirin for thromboprophylaxis Distal leg DVT: not all patients need anticoagulant treatment (no extension within 2 w, no factors present such as pos DD, close to popliteal vein, no reversible provoking factor, active cancer, previous VTE event, and inpatient status) Anticoagulant treatment while awaiting lab or imaging results: previously: only if clinical probability high now: also if clinical probability intermediate and waiting time >4hs

16 9 th ACCP Guidelines (2012) Guidelines fail clinicians? (IV) Duration of anticoagulant treatment following DVT/PE

17 9 th ACCP Guidelines (2012) Guidelines fail clinicians? (V) Duration of anticoagulant treatment following DVT/PE

18 9 th ACCP Guidelines (2012) Guidelines fail clinicians? (VI) Evaluation of bleeding risk on anticoagulant therapy

19 9 th ACCP Guidelines (2012) Guidelines fail patients? A few examples of patient-relevant recommendations LMWH rather than warfarin during pregnancy Take frequent pregnancy tests and switch from warfarin to LMWH after becoming pregnant Continue warfarin or UFH for breastfeeding women Wear elastic stockings for at least 2 years after a DVT and continue if symptoms are still present after 2 years...

20 Are AT9 truly international guidelines? Executive Committee Panelists 5 members 116 members 3 from McMaster Canada: 32 (23 McM*) 2 from the US US: 54 Europe: 27 ROW: 3 *AGG Turpie panelist 1992, 1995, 1998

21 From Eminence-based to Evidence-Based Medicine «Follow me» «Follow the unbiased evidence»

22 Conclusions EBM-Guidelines are necessary in the field of antithrombotic prophylaxis and therapy The ACCP guidelines have an excellent reputation in this field The innovations introduced in AT9 are positive and will contribute to the pertinence of the guidelines (with few exceptions) both for clinicians and patients Rather than criticizing the guidelines, what is now needed is enforcing their implementation

23 Thank you for your attention