Re: Transcatheter or surgical aortic valve replacement for patients with severe, symptomatic, aortic stenosis at low to intermediate surgical risk: a clinical practice guideline
In their letter, Yates, Uppal and Roberts state that there is no evidence to support the BMJ Rapid Recommendations for transfemoral aortic valve implantation (TAVI) in patients 75 years or older with severe symptomatic aortic stenosis (AS), at low or intermediate perioperative risk. We respectfully disagree as we report evidence of moderate to high quality for a benefit of TAVI for critical outcomes such as death and stroke and recognized the low quality evidence for another patient-important outcome, namely long term durability of TAVI-valves.1 Thoracic surgeons and others may well come to different conclusions after careful assessment of best current evidence. We believe an explanation of how we arrived at our age-stratified recommendations may be helpful, as previously outlined in The BMJ and in MAGICapp.(1,2)
BMJ Rapid Recommendations are developed according to widely accepted standards for trustworthy guidelines.(3) Beyond emphasizing key standards - such as managing conflicts of interests and involving patients in the process - we rigorously apply the GRADE system to rate certainty in best current evidence and to move from evidence to recommendations in a systematic and transparent manner.(4) The multidisciplinary guideline panel started by defining our clinical question in a PICO format as follows: (P) Adults with symptomatic severe AS at low to intermediate surgical risk; (I) TAVI; (C ) surgical aortic valve replacement (SAVR); (O) 14 important outcomes pre-defined by the guideline panel. A separate group then performed a high quality systematic review and meta-analysis of best current evidence. The systematic review included three well performed randomised controlled trials that compared outcomes with transfemoral TAVI versus SAVR, including 2576 patients at low to intermediate risk with a mean age of 81 years.(5)We also considered long term outcomes and durability of SAVR based on observational studies, published in a linked systematic review in the same issue of the BMJ.6
Readers can access detailed evidence summaries from the systematic review (GRADE Summary of Findings tables) in The BMJ publications and in MAGICapp, an online authoring and publication platform and clinical decision support tool.(1, 5-8) These evidence summaries support our age-stratified recommendations and display relative risks, absolute effects estimates and the certainty of the effect estimates for each outcome, stratified into 4 age groups. Rating of certainty is performed according to GRADE by the guideline panel and reflects to what extent the effect-estimates reported in the meta-analysis reflect the true effects of treatment.
The letter’s authors discount the applicability of relative effects from randomised trials with an older mean age (81 years) to patients aged 75 to 85 years. We believe the relative effects will be similar and indeed, directly applicable to patients aged 75 to 85 years. They also question the applicability of evidence from patients at low and intermediate surgical risk to patients at lower risk. Subgroup analyses of randomised trials that enrolled patients at lower risk versus intermediate risk, (9,2) as well as within trial subgroup analyses, (10,11) suggest that the relative effects are similar for patients at intermediate and lower risk. The letter authors also apparently put a higher credibility on observational studies than randomised trials. We believe the latter have higher credibility. The letter’s authors believe that, faced with, over two years, a likely relative decrease in mortality of 21% (absolute approximately 3%), a likely relative decrease in stroke of 20% (absolute approximately 2%), a relative decrease in acute kidney injury of 62% (absolute approximately 5%) and a relative decrease in life-threatening or disabling bleeding of 61% (absolute approximately 25%) with TAVI versus SAVR, all or almost all patients in all age groups would choose, on the basis of speculative superiority over the long term, SAVR. We think, for patients over 65, they are wrong in their inference, and increasingly misguided in progressively older patients. Shared decision making, based on our evidence summaries, in those between 65 and 85 would establish whether the letter authors, or ourselves, have a better sense of patients’ values and preferences.
We agree that SAVR remains the procedure of choice in younger patients; with a strong recommendation for SAVR in those under age 65 years and a weak recommendation for SAVR in those age 65 to 75 years. Currently, we have limited data on durability of TAVI valves beyond 5 years. This is an important consideration given that most patients would likely choose a transcatheter-based option over surgery when a transfemoral approach is feasible. In contrast to transfemoral TAVI, comparison of outcomes with transapical TAVI versus SAVR strongly support SAVR as the preferred option, as detailed in our recommendations.
Clinicians and patients already are making decisions about TAVI versus SAVR, even in patients at lower surgical risk; we hope the BMJ Rapid Recommendations provide a helpful framework and that the clinical decision support tools can be used now to involve patients meaningfully in the decision making process. Neither the 2012 European Society of Cardiology or American College of Cardiology valvular heart disease guidelines addressed TAVI for patients at lower surgical risk, but several practice-changing studies have been approved in the interim and TAVI is approved for use in intermediate risk patients in the US.(12,13) We hope that updated versions of those guidelines will address this important clinical issue soon. In the meanwhile, the BMJ Rapid Recommendations are available to all.
Per Olav Vandvik
Catherine M. Otto
Reed A. Siemieniuk
Gordon H. Guyatt
Frederick A. Spencer
1. Vandvik PO, Otto CM, Siemieniuk RA, et al. Transcatheter or surgical aortic valve replacement for patients with severe, symptomatic, aortic stenosis at low to intermediate surgical risk: a clinical practice guideline. BMJ 2016;354:i5085.
2. Siemieniuk RA, Macdonald H, Agoritsas T, Guyatt GH, Vandvik PO. Introduction to BMJ Rapid Recommendations. BMJ 2016;354:i5191, doi:10.1136/bmj.i5191
3. Laine C, Taichman DB, Mulrow C. Trustworthy clinical guidelines. Annals of internal medicine. 2011;154(11):774-775.
4. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. Bmj. 2008;336(7650):924-926.
5. Siemieniuk RA, Agoritsas T, Manja V, et al. Transcatheter versus surgical aortic valve replacement in patients with severe aortic stenosis at low and intermediate risk: systematic review and meta-analysis. BMJ 2016;354:i5130
6. Foroutan F, Guyatt GH, O´Brien K, et al. Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe aortic stenosis: systematic review of observational studies. BMJ 2016;354:i5065
7. Vandvik PO, Brandt L, Alonso-Coello P, et al. Creating clinical practice guidelines we can trust, use, and share: a new era is imminent. Chest. 2013;144(2):381-389.
8. BMJ Rapid Recommendations for Transcatheter Aortic Valve Implantation. https://www.magicapp.org/app#/guideline/1294
9. Søndergaard L, Steinbrüchel DA, Ihlemann N, et al. Two-Year Outcomes in Patients With Severe Aortic Valve Stenosis Randomized to Transcatheter Versus Surgical Aortic Valve Replacement: The All-Comers Nordic Aortic Valve Intervention Randomized Clinical Trial. Circ Cardiovasc Interv. 2016 Jun;9(6). pii: e003665. doi: 10.1161/CIRCINTERVENTIONS.115.003665
10. Leon MB, Smith CR, Mack MJ, et al. PARTNER 2 Investigators. Transcatheter or Surgical Aortic-Valve Replacement in Intermediate Risk Patients. N Engl J Med 2016; 374:1609-20
11. Reardon MJ, Kleiman NS, Adams DH, et al. Outcomes in the Randomized CoreValve US Pivotal High Risk Trial in Patients With a Society of Thoracic Surgeons Risk Score of 7% or Less. JAMA Cardiol. 2016 Nov 1;1(8):945-949. doi: 10.1001/jamacardio.2016.2257.
12. Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC).; European Association for Cardio-Thoracic Surgery (EACTS)., Vahanian A, Alfieri O, Andreotti F, Antunes MJ, Barón-Esquivias G, Baumgartner H, Borger MA, Carrel TP, De Bonis M, Evangelista A, Falk V, Iung B, Lancellotti P, Pierard L, Price S, Schäfers HJ, Schuler G, Stepinska J, Swedberg K, Takkenberg J, Von Oppell UO, Windecker S, Zamorano JL, Zembala M. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J. 2012 Oct;33(19):2451-96. doi: 10.1093/eurheartj/ehs109.
13. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, O'Gara PT, Ruiz CE, Skubas NJ, Sorajja P, Sundt TM 3rd, Thomas JD; American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2014 AHA/ACC guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jun 10;63(22):2438-88. doi: 10.1016/j.jacc.2014.02.537. Erratum in: J Am Coll Cardiol. 2014 Jun 10;63(22):2489.
Competing interests: No competing interests