Linee Guida ACCP Opinioni a Confronto A Favore

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1 XXIV CONGRESSO NAZIONALE FCSA Bologna 9 Ottobre 2013 Linee Guida ACCP Opinioni a Confronto A Favore Francesco Dentali Dipartimento di Medicina Clinica, Università dell'insubria, Ospedale di Circolo, Varese

2 ACCP 2012 (9th edition) In patients undergoing THA or TKA, we recommend use of one of the following for a minimum of 10 to 14 days rather than no antithrombotic prophylaxis: LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, LDUH, adjusted-dose VKA, aspirin (all Grade 1B), or IPCD (Grade 1C). Falck-Itter et al, CHEST 2012

3 1A

4 Antithrombotic Therapy for VTE A 36 1B 4 1C 34 2A 0 2B 15 2C 21

5 Antithrombotic Therapy for VTE A 0 1B 48 1C 2 2A 0 2B 28 2C 48

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8 Premessa the guidelines more than kept pace with advances in the science of guideline methodology and continued to improve with each iteration. Each new edition provided a model incorporating not only the latest evidence regarding antithrombotic therapy but also advances in specialty-based guidelines and therefore maintained preeminence in the field of thrombosis.

9 Premessa (II) as Dr Hirsh was stepping down from the leadership of the guidelines in 2007, his insight led him to question the reliance on expert opinion that provided the basis for the first eight iterations of the antithrombotic Guidelines.

10 Premessa (III) Dr Hirsh concluded that the conflict of interest of leading experts was highly problematic. Furthermore, the problem arose not only from their financial but equally or perhaps more important, their intellectual conflict of interest

11 Premessa (IV) This revelation and the changes in process that Dr Hirsh suggested as a solution to the problem had a profound impact on the leadership to whom he was passing the torch. These changes underlie all the innovations in AT9

12 Dealing with conflict of interest The solution was to give primary leadership and responsibility for each article not to a thrombosis expert but to a methodologist (with a specific training in ACCP s approach to rating the quality of evidence and grading strength of recommendations) who, in almost all cases, also is a practicing physician without important conflicts of interest

13 Dealing with conflict of interest (ii) The process stipulated that although conflicted thrombosis experts could engage in discussion and even draft evidence summaries, they would be excluded from the final decisions regarding quality of evidence and direction and strength of recommendations. Intellectual conflicts received the same attention as financial conflicts.

14 Struttura di base

15 Development Steps

16 Development Steps (ii)

17 PICO Patients Intervention Control Outcome

18 Identifying the Evidence To identify the relevant evidence, a team of methodologist and medical librarians conducted literature searches of Medline, the Cochrane Library, and the Database of Abstracts of Reviews of Effects. For each article, the team conducted a search for systematic reviews and another for original studies encompassing the main populations and interventions for that article.

19 Novità

20 Evidence Summaries Evidence profiles Summary of findings

21 Evidence Profiles These tables summarize the quality of a body of evidence for each relevant outcome and, when evidence comes from randomized trials, include a presentation of reviewers assessment of risk of bias, precision, consistency, directness, and publication bias (online data supplements)

22 Grade Approach to rating quality of Evidence

23 Summary of Findings The more succinct summary of findings tables, which include the overall quality assessment as well as relative and absolute effect sizes for each outcome.

24 Estimating the Relative and Absolute Effects Relative effects are similar across subgroups of patients, including those with varying baseline risk Trading off desirable and undesirable consequences (eg, thrombosis vs bleeding) requires, however, estimates of absolute effect.

25 Relative and Absolute Effects For example, in AF patients, warfarin results in a 66% RRR in nonfatal stroke. This comes at a cost of inconvenience, lifestyle restrictions, and risk of bleeding.

26 Relative and Absolute Effects (ii) Patients with a CHADS score of 3, - The 66% relative risk reduction translates into an absolute reduction of 6.3% (63 in 1,000) per year. - Virtually all patients will consider this worthwhile.

27 Relative and Absolute Effects (i) Patients with a CHADS score of 0, - The 66% reduction translates into an absolute risk reduction of only 0.5% (5 in 1,000) per year. - Many patients may consider this reduction not worth the undesirable consequences of warfarin use.

28 Conducting Meta-analyses When pooled estimates of effects were not available from existing high-quality systematic reviews, we performed meta-analyses if the data were sufficiently homogeneous. Studies were pooled using fixed-effects or random effects model.

29 Composite Endpoints When the patient importance of the component end points and the magnitude of effect of the intervention on the components differ, these can be misleading. Results and base inferences on the effect of interventions were presented on individual outcomes

30 Reevaluation of the Evidences Patient-important Outcomes Surrogate Outcomes

31 Asymptomatic distal DVT Major Bleeding Trade-Off?

32 Frontline Clinicians Each panel included a frontline clinician not involved in thrombosis research.

33 Frontline Clinicians (ii) The goal of including these individuals was to ensure that recommendations considered the full realities of clinical practice as viewed by those outside the research environment and to support efforts to make the phrasing of recommendations more user friendly and implementable.

34 Frontline Clinicians These clinicians were charged with the following: Proposing important real-world clinical questions on the prevention, diagnosis, and treatment of thrombosis that were not addressed in AT8 Reviewing the draft manuscripts and recommendations to assess the usability of the guidelines and the feasibility of implementation of AT9 recommendations.

35 Bleeding Risk A limitation of AT8 was the very inconsistent approaches to assessing bleeding risk. In the AT9 approach to bleeding was consistently applied across chapters

36 Bleeding Risk (ii) One individual (S. S.) was responsible for standardizing the approach to bleeding outcomes. Minor Bleeding events were not considered

37 Economic Efficiency Resource use consultants were included on the AT9 article panels charged with making recommendations. They developed a transparent and systematic methodology to address questions for which resource use might change the direction or strength of recommendations.

38 Economic Efficiency (ii) Economic evaluation was restricted to recommendations in which it was plausible that resource use considerations might change the direction or strength of the recommendation and in which high quality economic evaluations were available. When this was not the case, resource use in the recommendations was not considered.

39 Diagnosis For the first time, issues of diagnosis was addressed in the antithrombotic guidelines

40 Patients Values and Preferences Little is known regarding patient values and preferences for and experiences with antithrombotic therapy (including prophylaxis and treatment).

41 Patients Values and Preferences (ii) Values and preferences for AT and for health states appear to vary appreciably among individuals. A reasonable trade-off to assume between stroke and bleeds would be a ratio of disutility of net nonfatal stroke to GI bleeds in the range of 2:1 to 3:1. Less information about the relative disutility of MI, VTE and bleeds.

42 Patients Values and Preferences (iii) VKA therapy does not have important negative effects on quality of life, although many patients worry about the side effects associated with this treatment. Patient aversion to warfarin treatment may decrease over time after treatment is initiated. Injection treatments are well tolerated.

43 in conclusione

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45 Diagnostic/Therapeutic Uncertainty Literature Research - Systematic Reviews - (Clinical Practice) Guidelines Clinical Decision

46 Diagnostic/Therapeutic Uncertainty Literature Research - Systematic Reviews - (Clinical Practice) Guidelines Clinical Decision???

47 ACCP 2008 (8th edition) We recommend against the use of aspirin alone as thromboprophylaxis against VTE for any patient group (grade 1A) Geerts et al, CHEST 2008

48 ACCP 2012 (9th edition) In patients undergoing THA or TKA, we recommend use of one of the following for a minimum of 10 to 14 days rather than no antithrombotic prophylaxis: LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, LDUH, adjusted-dose VKA, aspirin (all Grade 1B), or IPCD (Grade 1C). Falck-Itter et al, CHEST 2012

49 ACCP 2012 (9th edition) In patients undergoing THA or TKA, we suggest the use of LMWH in preference to the other agents we have recommended as alternatives: fondaparinux, apixaban, dabigatran, rivaroxaban, LDUH (all Grade 2B), adjusted-dose VKA, or aspirin (all Grade 2C) Falck-Itter et al, CHEST 2012

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