Current evidence for prosthesis selection: What can we really say?

Abstract

Central MessageAlthough implantation of biologic aortic valve prostheses may be appropriate in patients as young as 55 years of age, enthusiasm for biologic mitral valve prostheses may need to be tempered.The Invited Expert Opinion provides a perspective on this topic based on the following paper: N Engl J Med. 2017;377:1847-57. DOI: 10.1056/NEJMoa1613792.See Commentary on page 376. Although implantation of biologic aortic valve prostheses may be appropriate in patients as young as 55 years of age, enthusiasm for biologic mitral valve prostheses may need to be tempered. The Invited Expert Opinion provides a perspective on this topic based on the following paper: N Engl J Med. 2017;377:1847-57. DOI: 10.1056/NEJMoa1613792. See Commentary on page 376. Deciding between a mechanical and a biologic valve prosthesis for valve replacement has been a perennial challenge for patients and surgeons alike. Although mechanical valve prostheses have a long track record of durability, these valves also require lifelong anticoagulation to prevent thromboembolic complications and thus carry a concomitant increased risk of bleeding. In contrast, biologic valve prostheses do not require long-term anticoagulation but have a higher incidence of reoperation for structural valve deterioration. Balancing these risks is a challenge that must be personalized to the individual patient. The earliest efforts to evaluate the comparative effectiveness of mechanical and biologic valve prostheses were the Edinburgh Heart Valve Trial and the Veterans Affairs Cooperative Study on Valvular Heart Disease.1Bloomfield P. Wheatley D.J. Prescott R.J. Miller H.C. Twelve-year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses.N Engl J Med. 1991; 324: 573-579Crossref PubMed Scopus (318) Google Scholar, 2Hammermeister K.E. Sethi G.K. Henderson W.G. Oprian C. Kim T. Rahimtoola S. A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. Veterans affairs cooperative study on valvular heart disease.N Engl J Med. 1993; 328: 1289-1296Crossref PubMed Scopus (380) Google Scholar In the Edinburgh Heart Valve Trial, patients undergoing aortic or mitral valve replacement were randomized to the Bjork-Shiley mechanical valve prosthesis (Shiley Inc, Irvine, Calif) or a biologic valve prosthesis, initially the Hancock porcine valve (Medtronic Inc, Minneapolis, Minn) and later the Carpentier-Edwards porcine valve (Edwards Lifesciences, Irvine, Calif). At 12 years, there was no difference in survival but an increased risk of reoperation among patients who received a biologic valve prosthesis (8.5% vs 37.1%, P < .001).1Bloomfield P. Wheatley D.J. Prescott R.J. Miller H.C. Twelve-year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses.N Engl J Med. 1991; 324: 573-579Crossref PubMed Scopus (318) Google Scholar The Veterans Affairs Cooperative Study similarly randomized patients to the Bjork-Shiley mechanical heart valve or the Hancock porcine biologic prosthesis. Similar to the Edinburgh Heart Valve Trial, there was no difference in survival at 11 years, but there was an increased risk of structural valve failure with biologic prostheses compared with mechanical prostheses. Notably, there was a difference in the risk of structural valve deterioration for biologic valves depending on the implanted position with a 15% probability of structural valve failure for biologic prostheses in the aortic valve position at 11 years compared with a 36% probability in the mitral valve position.2Hammermeister K.E. Sethi G.K. Henderson W.G. Oprian C. Kim T. Rahimtoola S. A comparison of outcomes in men 11 years after heart-valve replacement with a mechanical valve or bioprosthesis. Veterans affairs cooperative study on valvular heart disease.N Engl J Med. 1993; 328: 1289-1296Crossref PubMed Scopus (380) Google Scholar Both trials recommended that most patients undergoing mitral valve replacement and younger patients undergoing aortic valve replacement receive mechanical valve prostheses. In the years after these 2 landmark trials, single-institution studies demonstrating adequate performance of biologic prostheses with low rates of reoperation were published.3Cohn L.H. Collins Jr., J.J. DiSesa V.J. Couper G.S. Peigh P.S. Kowalker W. et al.Fifteen-year experience with 1678 Hancock porcine bioprosthetic heart valve replacements.Ann Surg. 1989; 210: 435-443Crossref PubMed Scopus (102) Google Scholar, 4Burdon T.A. Miller D.C. Oyer P.E. Mitchell R.S. Stinson E.B. Starnes V.A. et al.Durability of porcine valves at fifteen years in a representative North American patient population.J Thorac Cardiovasc Surg. 1992; 103: 238-252Abstract Full Text PDF PubMed Google Scholar Together with the randomized data, these findings led to the publication of professional guidelines in 1998 containing a class IIa recommendation that patients aged 65 years or less receive mechanical valves in the aortic position and that patients aged 70 years or less receive mechanical valves in the mitral position (Table 1).5ACC/AHA guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association. Task force on practice guidelines (Committee on management of patients with valvular heart disease).J Am Coll Cardiol. 1998; 32: 1486-1588Crossref PubMed Google Scholar Further, a class IIb recommendation existed for biologic valve prostheses in either position for patients younger than 65 years old.Table 1Evolution of guidelines for prosthesis selection in valve replacementAVRMVRMechanicalBiologicMechanicalBiologicBonow, 19985ACC/AHA guidelines for the management of patients with valvular heart disease. A report of the American College of Cardiology/American Heart Association. Task force on practice guidelines (Committee on management of patients with valvular heart disease).J Am Coll Cardiol. 1998; 32: 1486-1588Crossref PubMed Google Scholar<65 yIIa≥65 yI≤ 70 yIIa>70 yIIa<65 yIIb<65 yIIbMechanicalBiologicBonow, 20068American College of Cardiology American Heart Association Task Force on Practice Group Society of Cardiovascular Association Bonow R.O. Carabello B.A. Chatterjee K. et al.ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.J Am Coll Cardiol. 2006; 48: e1-e148PubMed Google Scholar<65 yIIa≥65 yIIa<65 y∗For lifestyle considerations after detailed discussions of the risks of anticoagulation versus the likelihood of a second valve replacement.IIaBonow, 200845Bonow R.O. Carabello B.A. Chatterjee K. de Leon Jr., A.C. Faxon D.P. Freed M.D. et al.2008 focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons..Circulation. 2008; 118: e523-e661Crossref PubMed Scopus (1152) Google Scholar<65 yIIa≥65 yIIa<65 y∗For lifestyle considerations after detailed discussions of the risks of anticoagulation versus the likelihood of a second valve replacement.IIaNishimura, 201418Nishimura R.A. Otto C.M. Bonow R.O. Carabello B.A. Erwin III, J.P. Guyton R.A. et al.2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines.J Am Coll Cardiol. 2014; 63: e57-e185Crossref PubMed Scopus (2093) Google Scholar<60 yIIa>70 yIIaNishimura, 201719Nishimura R.A. Otto C.M. Bonow R.O. Carabello B.A. Erwin 3rd, J.P. Fleisher L.A. et al.2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines.J Am Coll Cardiol. 2017; 70: 252-289Crossref PubMed Scopus (1826) Google Scholar<50 yIIa>70 yIIaAVR, Aortic valve replacement; MVR, mitral valve replacement.∗ For lifestyle considerations after detailed discussions of the risks of anticoagulation versus the likelihood of a second valve replacement. Open table in a new tab AVR, Aortic valve replacement; MVR, mitral valve replacement. Subsequent publication of the long-term results arising from the Veterans Affairs Cooperative Study on Valvular Heart Disease and the Edinburgh Heart Valve Trial suggested that mechanical valve prosthesis implantation was associated with reduced risk of reoperation in both the aortic and mitral valve positions.6Hammermeister K. Sethi G.K. Henderson W.G. Grover F.L. Oprian C. Rahimtoola S.H. Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the veterans affairs randomized trial.J Am Coll Cardiol. 2000; 36: 1152-1158Crossref PubMed Scopus (901) Google Scholar, 7Oxenham H. Bloomfield P. Wheatley D.J. Lee R.J. Cunningham J. Prescott R.J. et al.Twenty year comparison of a Bjork-Shiley mechanical heart valve with porcine bioprostheses.Heart. 2003; 89: 715-721Crossref PubMed Scopus (265) Google Scholar However, these valves, having been implanted between 1975 and 1982, were no longer in use. Contemporary evidence arising from single-institution studies revealed a lower incidence of structural valve deterioration compared with the biologic valves used in these early trials, thereby introducing controversy regarding prosthesis selection. Subsequently, professional guidelines published in 2006 were amended to strengthen the recommendation for patients aged less than 65 years to receive biologic prostheses (IIa) in the setting of lifestyle considerations “after detailed discussions of the risks of anticoagulation versus the likelihood that a second [aortic valve replacement] may be necessary in the future” (Table 1).8American College of Cardiology American Heart Association Task Force on Practice Group Society of Cardiovascular Association Bonow R.O. Carabello B.A. Chatterjee K. et al.ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.J Am Coll Cardiol. 2006; 48: e1-e148PubMed Google Scholar At this point, selection of a mechanical or biologic aortic valve prosthesis was considered “reasonable” (class IIa recommendation) for patients aged less than 65 years (Table 1).8American College of Cardiology American Heart Association Task Force on Practice Group Society of Cardiovascular Association Bonow R.O. Carabello B.A. Chatterjee K. et al.ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.J Am Coll Cardiol. 2006; 48: e1-e148PubMed Google Scholar In New York State between 1997 and 2004, the proportion of biologic prostheses implanted in the aortic position increased from 15% to 74% among patients aged 50 to 70 years, and this was mirrored both in Sweden (17% between 1997 and 2002 to 58% between 2006 and 2013) and California (12% to 52% between 1996 and 2013) for similarly aged patients9Chiang Y.P. Chikwe J. Moskowitz A.J. Itagaki S. Adams D.H. Egorova N.N. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years.JAMA. 2014; 312: 1323-1329Crossref PubMed Scopus (196) Google Scholar, 10Glaser N. Jackson V. Holzmann M.J. Franco-Cereceda A. Sartipy U. Aortic valve replacement with mechanical vs. biological prostheses in patients aged 50-69 years.Eur Heart J. 2016; 37: 2658-2667Crossref PubMed Scopus (158) Google Scholar, 11Goldstone A.B. Chiu P. Baiocchi M. Lingala B. Patrick W.L. Fischbein M.P. et al.Mechanical or biologic prostheses for aortic-valve and mitral-valve replacement.N Engl J Med. 2017; 377: 1847-1857Crossref PubMed Scopus (336) Google Scholar (Figure 1, A). The seeming ambivalence of the guideline was effectively an endorsement of the increasingly aggressive implantation of biologic prostheses in younger patients. In the years following, evidence demonstrating improved durability of biologic prostheses continued to be published. The University of Toronto reported in a retrospective series a 5.9% risk of reoperation at 15 years for patients aged 60 to 70 years.12David T.E. Armstrong S. Maganti M. Hancock II bioprosthesis for aortic valve replacement: the gold standard of bioprosthetic valves durability?.Ann Thorac Surg. 2010; 90: 775-781Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar The Cleveland Clinic Foundation also reported their single-institution experience with a 5.1% risk of valve explantation for structural valve deterioration among patients aged 60 to 80 years.13Johnston D.R. Soltesz E.G. Vakil N. Rajeswaran J. Roselli E.E. Sabik III, J.F. et al.Long-term durability of bioprosthetic aortic valves: implications from 12,569 implants.Ann Thorac Surg. 2015; 99: 1239-1247Abstract Full Text Full Text PDF PubMed Scopus (314) Google Scholar Furthermore, Stassano and colleagues14Stassano P. Di Tommaso L. Monaco M. Iorio F. Pepino P. Spampinato N. et al.Aortic valve replacement: a prospective randomized evaluation of mechanical versus biological valves in patients ages 55 to 70 years.J Am Coll Cardiol. 2009; 54: 1862-1868Crossref PubMed Scopus (207) Google Scholar randomized 310 patients aged 55 to 70 years to receive a biologic or mechanical prosthesis for aortic valve replacement. There was no difference in survival to 13 years after surgery (P = .2), but there was a difference in the rate of reoperation (0.62%/patient-year for mechanical prostheses vs 2.32%/patient-year for biologic prostheses, P < .001). Together, these data were encouraging for the expanded use of biologic valve prostheses in younger patients. Evidence similarly emerged that contemporary biologic valve prostheses in the mitral position were less prone to failure compared with the devices used in the randomized trials. Although the Veterans Affairs Cooperative Study reported 50% probability of mitral valve reoperation at 15 years,6Hammermeister K. Sethi G.K. Henderson W.G. Grover F.L. Oprian C. Rahimtoola S.H. Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the veterans affairs randomized trial.J Am Coll Cardiol. 2000; 36: 1152-1158Crossref PubMed Scopus (901) Google Scholar the second-generation Carpentier-Edwards PERIMOUNT valve experienced 95.2% freedom from structural valve deterioration at 10 years among patients aged 61 to 70 years compared with 75.2% for first- and second-generation devices (P < .05), respectively.15Eric Jamieson W.R. Marchand M.A. Pelletier C.L. Norton R. Pellerin M. Dubiel T.W. et al.Structural valve deterioration in mitral replacement surgery: comparison of Carpentier-Edwards supra-annular porcine and Perimount pericardial bioprostheses.J Thorac Cardiovasc Surg. 1999; 118: 297-304Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar During this period, surgeons implanted an increasing number of biologic mitral valve prostheses in patients. In New York State, the proportion of biologic valve prostheses implanted increased from 8% to 60% between 1997 and 2012 for patients aged 50 to 70 years16Chikwe J. Chiang Y.P. Egorova N.N. Itagaki S. Adams D.H. Survival and outcomes following bioprosthetic vs mechanical mitral valve replacement in patients aged 50 to 69 years.JAMA. 2015; 313: 1435-1442Crossref PubMed Scopus (85) Google Scholar; in the state of California, there was an increase from 17% to 54% between 1996 and 2013 among all age ranges (Figure 1, B).11Goldstone A.B. Chiu P. Baiocchi M. Lingala B. Patrick W.L. Fischbein M.P. et al.Mechanical or biologic prostheses for aortic-valve and mitral-valve replacement.N Engl J Med. 2017; 377: 1847-1857Crossref PubMed Scopus (336) Google Scholar The 2006 guidelines were subsequently amended to lower the age recommendation for reasonable use of a biologic mitral valve prosthesis to 65 years, the same as the aortic position (Table 1).8American College of Cardiology American Heart Association Task Force on Practice Group Society of Cardiovascular Association Bonow R.O. Carabello B.A. Chatterjee K. et al.ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (writing committee to Revise the 1998 guidelines for the management of patients with valvular heart disease) developed in collaboration with the Society of Cardiovascular Anesthesiologists endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons.J Am Coll Cardiol. 2006; 48: e1-e148PubMed Google Scholar Single-center retrospective cohort studies suggested that contemporary valve prostheses might be superior to those implanted in early randomized controlled trials; however, the lack of a direct comparison was a significant limitation. One of the earliest attempts to use modern statistical methods to create a head-to-head comparison between biologic and mechanical valve prostheses was by Brown and colleagues17Brown M.L. Schaff H.V. Lahr B.D. Mullany C.J. Sundt T.M. Dearani J.A. et al.Aortic valve replacement in patients aged 50 to 70 years: improved outcome with mechanical versus biologic prostheses.J Thorac Cardiovasc Surg. 2008; 135: 878-884Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar from the Mayo Clinic comparing matched patients between 50 and 70 years of age receiving biologic or mechanical aortic valve prostheses. The investigators found that patients receiving a mechanical aortic valve had superior mid-term survival. However, there was a statistically significant difference in the risk of perioperative mortality (mechanical vs biologic prosthesis: 1.8% vs 5.5%, P = .04), and there was no difference in freedom from reoperation between mechanical and biologic prostheses at 10 years: 97.5% versus 91% (P = .1). These results with respect to perioperative mortality and reoperation were distinctly different from randomized data; whether the analysis was affected by selection bias is uncertain. The 2014 guidelines further liberalized the prosthesis selection criteria and introduced a grey zone in which either valve was considered to be appropriate for patients 60 to 70 years of age (Table 1).18Nishimura R.A. Otto C.M. Bonow R.O. Carabello B.A. Erwin III, J.P. Guyton R.A. et al.2014 AHA/ACC guideline for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association task force on practice guidelines.J Am Coll Cardiol. 2014; 63: e57-e185Crossref PubMed Scopus (2093) Google Scholar This relaxation of the guideline represented a de facto endorsement of the ongoing trend toward performing more biologic valve prosthesis implantations in progressively younger patients for both the aortic and mitral valves. Shortly thereafter, 3 landmark observational studies were published. The first of these was a propensity score–matched study featuring 1001 matched pairs undergoing aortic valve replacement with a mechanical or biologic valve prosthesis between 1997 and 2004. Using the Statewide Planning and Research Cooperative System from New York State, Chiang and colleagues9Chiang Y.P. Chikwe J. Moskowitz A.J. Itagaki S. Adams D.H. Egorova N.N. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years.JAMA. 2014; 312: 1323-1329Crossref PubMed Scopus (196) Google Scholar reported that there was no difference in survival between mechanical and biologic valve prostheses among patients 50 to 70 years of age. This finding suggested that the benefit due to mechanical aortic valve prostheses ended before age 50 years in a contemporary cohort of patients. Expected differences existed between patients with respect to risk of reoperation favoring mechanical prostheses (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.36-0.75), but there was also an increased risk of bleeding with mechanical prostheses (HR, 1.75; 95% CI, 1.27-2.43).9Chiang Y.P. Chikwe J. Moskowitz A.J. Itagaki S. Adams D.H. Egorova N.N. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years.JAMA. 2014; 312: 1323-1329Crossref PubMed Scopus (196) Google Scholar This finding was countered by Glaser and colleagues,10Glaser N. Jackson V. Holzmann M.J. Franco-Cereceda A. Sartipy U. Aortic valve replacement with mechanical vs. biological prostheses in patients aged 50-69 years.Eur Heart J. 2016; 37: 2658-2667Crossref PubMed Scopus (158) Google Scholar who used the Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies register between 1997 and 2013 to compare 1099 propensity-matched pairs. Biologic prostheses had a significantly higher mortality than mechanical prostheses in patients 50 to 70 years of age (HR, 1.34; 95% CI, 1.09-1.66; P = .006). In a subgroup analysis, there was an increased hazard of mortality with biologic prosthesis implantation than mechanical prosthesis implantation among patients 50 to 59 years of age (HR, 1.67; 95% CI, 1.06-2.61, P = .03) with no difference in the hazard of mortality among patients 60 to 69 years of age (HR, 1.08; 95% CI, 0.85-1.36, P = .5). Similar to the report by Chiang and colleagues,9Chiang Y.P. Chikwe J. Moskowitz A.J. Itagaki S. Adams D.H. Egorova N.N. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years.JAMA. 2014; 312: 1323-1329Crossref PubMed Scopus (196) Google Scholar there was an increased risk of reoperation associated with biologic prostheses (HR, 2.36; 95% CI, 1.42-3.94; P = .001) and reduced risk for bleeding (HR, 0.49; 95% CI, 0.34-0.70; P = .001).10Glaser N. Jackson V. Holzmann M.J. Franco-Cereceda A. Sartipy U. Aortic valve replacement with mechanical vs. biological prostheses in patients aged 50-69 years.Eur Heart J. 2016; 37: 2658-2667Crossref PubMed Scopus (158) Google Scholar The discordant results found in these 2 large studies may have been due to differences in longevity-related diseases between the cohorts from Sweden and New York State with greater incidence of diabetes, hypertension, atrial fibrillation, heart failure, and chronic obstructive pulmonary disease observed in the latter group. Of note, 15-year survival was similar between the 2 cohorts with mechanical prostheses: 62% compared with 59% in New York State and Sweden, respectively. In contrast, survival appeared to be different among patients undergoing biologic prosthesis implantation with 61% surviving at 15 years in New York State compared with 50% surviving at 15 years in Sweden.9Chiang Y.P. Chikwe J. Moskowitz A.J. Itagaki S. Adams D.H. Egorova N.N. Survival and long-term outcomes following bioprosthetic vs mechanical aortic valve replacement in patients aged 50 to 69 years.JAMA. 2014; 312: 1323-1329Crossref PubMed Scopus (196) Google Scholar, 10Glaser N. Jackson V. Holzmann M.J. Franco-Cereceda A. Sartipy U. Aortic valve replacement with mechanical vs. biological prostheses in patients aged 50-69 years.Eur Heart J. 2016; 37: 2658-2667Crossref PubMed Scopus (158) Google Scholar Without a direct comparative study between the 2 populations, reasons for this difference remain speculative. For mitral valve replacement, Chikwe and colleagues16Chikwe J. Chiang Y.P. Egorova N.N. Itagaki S. Adams D.H. Survival and outcomes following bioprosthetic vs mechanical mitral valve replacement in patients aged 50 to 69 years.JAMA. 2015; 313: 1435-1442Crossref PubMed Scopus (85) Google Scholar again used the Statewide Planning and Research Cooperative System database for New York to construct a propensity score–matched comparison consisting of 664 matched pairs undergoing mitral valve replacement between 1997 and 2004. The inference was similar to their aortic valve study, suggesting that there was no significant survival difference between biologic and mechanical valve prostheses in patients between 50 and 70 years old. Again, the risk of reoperation was lower for mechanical prostheses than biologic prostheses (HR, 0.59; 95% CI, 0.37-0.94; P = .03), and the risk of bleeding was greater (HR, 1.50; 95% CI, 1.05-2.16; P = .03).16Chikwe J. Chiang Y.P. Egorova N.N. Itagaki S. Adams D.H. Survival and outcomes following bioprosthetic vs mechanical mitral valve replacement in patients aged 50 to 69 years.JAMA. 2015; 313: 1435-1442Crossref PubMed Scopus (85) Google Scholar Professional guidelines were once again amended to lower the age of clinical equipoise to 50 years in 2017, independent of valve position (Table 1).19Nishimura R.A. Otto C.M. Bonow R.O. Carabello B.A. Erwin 3rd, J.P. Fleisher L.A. et al.2017 AHA/ACC focused update of the 2014 AHA/ACC guideline for the management of patients with valvular heart disease: A report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines.J Am Coll Cardiol. 2017; 70: 252-289Crossref PubMed Scopus (1826) Google Scholar However, whether the inference to be drawn from these studies was clinical equipoise among patients as young as 50 years of age is uncertain. Propensity score matching was used in each of the 3 observational studies outlined with exclusion of more than half of the patients given the use of a 1:1 matching algorithm. This technique selected only those patients receiving mechanical valve prostheses who were similar to patients receiving biologic valve prostheses, and thus excluded all of the patients for whom biologic valve prosthesis may have been considered an inappropriate choice. That these results might not be generalizable to all patients undergoing valve surgery greatly undermines the use of these studies to extend the age of clinical equipoise in the valve guidelines. Our group subsequently used California's Office of Statewide Health Planning and Development database between 1996 and 2013 to examine the comparative effectiveness of mechanical and biologic valve prostheses in both the aortic and mitral positions. In this study, inverse probability weighting was used with stabilized weights to achieve appropriate balance without excluding any patients. This allowed for estimation of the effect of all patients receiving one valve type or the other, that is, the average treatment effect20Stuart E.A. Matching methods for causal inference: a review and a look forward.Stat Sci. 2010; 25: 1-21Crossref PubMed Scopus (2750) Google Scholar; this represents the most pertinent question when attempting to formulate guidelines. Examining 9942 patients undergoing aortic valve replacement in the state of California, we demonstrated that those who underwent aortic valve replacement with a biologic prosthesis experienced an increased hazard of mortality up to age 55 years (among patients 45 to 54 years of age: HR, 1.23; 95% CI, 1.02-1.48, P = .03; among patients 55-64 years of age: HR, 1.04; 95% CI, 0.91-1.18; P = .60).11Goldstone A.B. Chiu P. Baiocchi M. Lingala B. Patrick W.L. Fischbein M.P. et al.Mechanical or biologic prostheses for aortic-valve and mitral-valve replacement.N Engl J Med. 2017; 377: 1847-1857Crossref PubMed Scopus (336) Google Scholar The cumulative incidence of bleeding was less for patients receiving biologic prostheses, but the cumulative incidence of reoperation was greater. This finding to some extent validated the decrease in the lower limit of acceptable age for biologic prosthesis implantation. An exploratory analysis evaluating age as a continuous variable demonstrated that at approximately 53 years of age, the hazard of death associated with biologic valve prosthesis implantation in the aortic valve position disappeared (Figure 2, A). We further examined 15,503 patients undergoing mitral valve replacement, and mortality was greater among patients receiving biologic valve prostheses compared with mechanical valve prostheses up to 70 years of age (HR, 1.16; 95% CI, 1.04-1.30; P = .01, among patients 50-69 years of age).11Goldstone A.B. Chiu P. Baiocchi M. Lingala B. Patrick W.L. Fischbein M.P. et al.Mechanical or biologic prostheses for aortic-valve and mitral-valve replacement.N Engl J Med. 2017; 377: 1847-1857Crossref PubMed Scopus (336) Google Scholar Similar to the aortic valve analysis, the cumulative i