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PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation

Part 2: Study results—prostheses, positions, and economic development
Open AccessPublished:August 01, 2022DOI:https://doi.org/10.1016/j.xjon.2022.07.011

      Abstract

      Objectives

      The Prospective Randomized On-X Mechanical Prosthesis Versus St Jude Medical Mechanical Prosthesis Evaluation (PROSE) trial purpose was to investigate whether a current-generation mechanical prosthesis (On-X; On-X Life Technologies/Artivion Inc) reduced the incidence of thromboembolic-related complications compared with a previous-generation mechanical prosthesis (St Jude Medical Mechanical Prosthesis; Abbott/St Jude Medical). This second report documents the valve-related complications by individual prostheses and by Western and Developing populations.

      Methods

      The PROSE trial study was conducted in 28 worldwide centers and incorporated 855 subjects randomized between 2003 and 2016. The study enrollment was discontinued on August 31, 2016. The study protocol, and analyses of 10 demographic variables and 24 risk factors were published in detail in 2021.

      Results

      The total patient population (N = 855) included patients receiving an On-X valve (n = 462) and a St Jude Medical valve (n = 393). The overall freedom evaluation showed no differences at 5 years between the prostheses for thromboembolism or for valve thrombosis. There were also no differences in mortality. There were several differences between Developing and Western populations. The freedom relations at 5 years for mortality favored Western over Developing populations. Valve thrombosis was differentiated by position and site: aortic < mitral (P = .007) and Western < Developing (P = .005). In the mitral position there were no cases in Western populations, whereas there were 8 in Developing populations (P = .217).

      Conclusions

      The On-X valve and St Jude Medical valve performed equally well in the study with no differences found. The only differentiation occurred with valve thrombosis in the mitral position more than the aortic position and occurring in Developing more than Western populations. The occurrence of valve thrombosis was also related to a younger population possibly due to anticoagulation compliance based on record review.

      Key Words

      Abbreviations and Acronyms:

      BMI (body mass index), CHF (congestive heart failure), INR (international normalized ratio), NYHA (New York Heart Association), PROSE (Prospective Randomized On-X Mechanical Prosthesis Versus St Jude Medical Mechanical Prosthesis Evaluation), TE (thromboembolism), VT (valve thrombosis)
      Figure thumbnail fx1
      On-X Prosthetic Heart Valve (On-X Life Technologies/Artivion Inc).
      The study valves performed equally well in the study with no differences found. Valve thrombosis occurred more often in mitral valves, Developing populations, and younger patients.
      This work documents the potential differences in thromboembolic event rates between 2 mechanical prostheses: an earlier-generation St Jude Medical valve and a more recent-generation On-X valve. The study assesses prostheses types and positions, as well as Western versus Developing countries based on the United Nations Human Development Index.
      The purpose of the Prospective Randomized On-X Prosthesis Versus St Jude Medical Prosthesis Evaluation (PROSE) study was to investigate whether a current-generation mechanical prosthesis (On-X Life Technologies/Artivion Inc) (Figure 1) reduced the incidence of thromboembolism (TE)-related complications compared with a previous-generation mechanical prosthesis (St Jude Medical Mechanical Prosthesis; Abbott/St Jude Medical Inc). The study hypothesis assessed the null and alternative hypotheses for a reduction in rate from 2% to 1%.
      Figure thumbnail gr1
      Figure 1On-X Prosthetic Heart Valve (On-X Life Technologies/Artivion Inc).

      Methods

      The study design of the PROSE trial was a multicenter, randomized trial with enrollment in 28 worldwide centers incorporating Western and Developing countries. The study used the United Nations Development Programme value for the Human Development Index arbitrarily as 0.9 and above for Western (ie, developed) countries and 0.75 and below for Developing countries. This categorization resulted in essentially a 50–50 split in the total study population.
      The study methods were published in detail in the Journal of Cardiothoracic Surgery in 2021,
      • Jamieson W.R.E.
      • Ely J.L.
      • Brink J.
      • Pennel T.
      • Bannon P.
      • Patel J.
      • et al.
      PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation: part 1(patient dynamics): preoperative demographics and preoperative and operative risk factors.
      including inclusion/exclusion criteria, sample size calculations, and all study procedures. This resulted in a randomized total patient population of 855 with an On-X population of 462 (54%) and a St Jude Medical population of 393 (46%). As previously described, this apparent difference resulted from a 2:1 randomization in the Australian center shifting the expected On-X percentage to 52% and the difference is not statistically significant.
      • Jamieson W.R.E.
      • Ely J.L.
      • Brink J.
      • Pennel T.
      • Bannon P.
      • Patel J.
      • et al.
      PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation: part 1(patient dynamics): preoperative demographics and preoperative and operative risk factors.
      Confirmation of randomness creating no clinically important bias was published in the prior paper. The study was registered with ClinicalTrials.gov as NCT000639782. The institutional review board or equivalent ethics committee of the University of British Columbia approved the study protocol and publication of data. The patient(s) provided informed written consent for the publication of the study data. All other sites were required to receive local ethics review before commencing enrollment. Renewals of ethics approvals were maintained throughout each center's participation.
      Study enrollment began in the Western cites during March 2003 and was slowed by a general reluctance from physicians and patients to randomization. Additionally, the Western populations were contributing too few mitral position patients to allow for valid analyses, so Developing country populations were added during March 2012. Enrollment ended in November 2015 in the Western sites and in August 2016 at all sites.
      The follow-up of patients occurred at discharge, 3 months, 6 months, at 1 year, and annually thereafter during the conduct of the study and the longitudinal evaluation to approximately 5 years, resulted in a total of 4078.1 patient-years of follow-up. Follow-up of patients was limited to 5 years for most patients, although data beyond 5 years was included when made available by an investigator. Data collected included information regarding adverse events as defined as the “Guidelines for reporting morbidity and mortality after cardiac valvular operations” of the Society of Thoracic Surgeons and the American Association for Thoracic Surgery.
      • Akins C.W.
      • Miller D.C.
      • Turina M.I.
      • Kouchoukos N.T.
      • Blackstone E.H.
      • Grunkemeier G.L.
      • et al.
      Guidelines for reporting mortality and morbidity after cardiac valve interventions.
      The target anticoagulation level for both prostheses was: for aortic position prostheses international normalized ratio (INR) between 2.2 and 2.8, and for mitral position prostheses INR between 2.5 and 3.5. No special effort was made to track INR values for each patient and control was left to standard of care at each site as a means of testing real-world results. The data analysis was performed using intent to treat, with no crossovers allowed in the trial. For the data analysis, the patients were included in the treatment group in which they were assigned.
      Primary end points were rate of major TE and valve thrombosis (VT), and secondary end points were rate of major hemorrhage and all-cause and valve-related mortality. Linearized occurrence rates were used to determine the performance of the prostheses regarding major TE events and major hemorrhage events. Kaplan-Meier analysis was used to evaluate the performance of the 2 prostheses regarding freedom from TE events at 5 years. A log-rank test was used to validate the significance of the Kaplan-Meier analysis. Multiple logistic regression analysis examined the relationship between important demographic variables and adverse event rates. The statistics features of Excel version 2202 (Microsoft) calculated rates, whereas all other statistics, including all P values, were performed by the authors using MedCalc Software Ltd version 20.023.
      The current documented thromboembolic rates with the On-X prosthesis came from the regulatory trials conducted for the Food and Drug Administration of the United States, and clinical studies.
      US Food and Drug Administration
      On-X valve summary of safety and effectiveness. PMA P000037, May 30, 2001, and PMA P000037 S002. March 6, 2002.
      • Palatianos G.M.
      • Laczkovics A.M.
      • Simon P.
      • Pomar J.L.
      • Birnbaum D.E.
      • Greve H.H.
      • et al.
      Multicentered European study on safety and effectiveness on the On-X prosthetic heart valve: intermediate follow-up.
      • McNicholas K.W.
      • Ivey T.D.
      • Metras J.
      • Szentpetery S.
      • Marra S.W.
      • Masters R.G.
      • et al.
      North American multicenter experience with the On-X prosthetic heart valve.
      • Laczkovics A.
      • Heidt M.
      • Oelert H.
      • Laufer G.
      • Greve H.
      • Pomar J.L.
      • et al.
      Early clinical experience with the On-X prosthetic heart valve.
      • Chan V.
      • Jamieson W.R.E.
      • Lam B.-K.
      • Ruel M.
      • Ling H.
      • Fradet G.
      • et al.
      Influence of the On-X mechanical prosthesis on intermediate-term major thromboembolism and hemorrhage: a prospective multicenter study.
      The TE rates for the St Jude Medical prosthesis are documented in the literature from publications over the past 20 years.
      • Emery R.W.
      • Krogh C.
      • Arom K.V.
      • Emery A.M.
      • Benyo-Albrecht K.
      • Joyce L.D.
      • et al.
      The St Jude Medical Cardiac Valve Prosthesis: a 25-year experience with single valve replacement.
      • Ikonomides J.S.
      • Krantz J.M.
      • Crumbley A.J.
      • Stroud M.R.
      • Bradley S.M.
      • Sade R.M.
      • et al.
      Twenty-year experience with the St Jude Medical valve prosthesis.
      • Arom K.V.
      • Emery R.W.
      • Petersen B.
      • Radosevich D.M.
      St Jude Medical valve prosthesis: health status of the patient after 15 years.
      • Emery R.W.
      • Arom K.V.
      • Kshettry V.R.
      • Kroshus T.J.
      • Von R.
      • Kersten T.E.
      • et al.
      Decision-making in the choice of heart valve for replacement in patients aged 60-70 years: twenty-year follow-up of the St Jude Medical aortic valve prosthesis.
      • Lund O.
      • Nielsen S.L.
      • Arildsen H.
      • Ilkjaer L.B.
      • Pilegaard H.K.
      Standard aortic St Jude valve at 18 years: performance profile and determinants of outcome.
      From the literature cited above, the weighted average of TE for all valve positions was 1.09% per patient-year On-X and 2.03% per patient-year for the St Jude Medical prosthesis. Thus, for the purpose of sample size calculations, the TE rate for the On-X prosthesis used was 1.0% per patient-year and that of the St Jude Medical prosthesis was 2.0% per patient-year. It was assumed that the treatment group (On-X prosthesis) would experience a 50% reduction in the incidence of major TE events relative to the St Jude Medical prosthesis group. An exponential maximum likelihood test of equality of survival curves with a 0.050 1-sided significance level would have 80% power to detect the difference between a rate of 0.0100 for the On-X prosthesis and a rate of 0.0200 for the St Jude Medical prosthesis, given a sample size of at least 250 patients in each group and follow-up of 5 years.
      The Adjudication Committee of the PROSE study consisted of the Data Safety Monitoring Board and the coordinating center principal investigator for the PROSE study at the Vancouver site. The primary end point adjudication was conducted blinded to the committee. This method of adjudication blinding of end point events is the only achievable method in a heart valve prosthesis study. The PROSE study utilized Case Report Forms for collection of the data. Each principal investigator monitored his or her center for severe adverse events as defined by the Society of Thoracic Surgeons and the American Association for Thoracic Surgery guidelines.
      • Akins C.W.
      • Miller D.C.
      • Turina M.I.
      • Kouchoukos N.T.
      • Blackstone E.H.
      • Grunkemeier G.L.
      • et al.
      Guidelines for reporting mortality and morbidity after cardiac valve interventions.
      The sponsor and each of the centers reported the serious adverse events to the appropriate governments, as required by each country's law for commercially distributed products. The PROSE study was performed according to the principals of the Helsinki Declaration and all patients received informed consent to those rules or more stringent rules as locally appropriate.
      The risks of valve replacement with either of these mechanical prostheses are those associated with all prosthetic replacement surgery, including TE, which was the focus of this study. The risks versus benefits of participating in the study was that patients (50% of patients) could turn out to receive a prosthesis type that was associated with fewer TE events than the other prosthesis type they could have received. The study was designed to determine which prosthesis was safer in terms of TE. The relative safety of the 2 prosthesis types was unknown before the trial, although both prostheses are approved for commercial use by Canadian and United States governments, and all major worldwide governments. The determination of the relative safety was the reason for the study.

      Results

      The total population for analysis in the PROSE trial was 855 patients implanted between 2003 and 2016. There were 939 patients screened for the trial. Of the trial patients, 16 discontinued/withdrew and 84 were lost to follow-up. The total population of On-X prosthesis recipients was 462 patients and the St Jude Medical recipient population was 393 patients. Patient follow-up in the trial was 4078.1 patient-years total: On-X n = 2219.8 and St Jude Medical n = 1858.3; Western population n = 2213.3 and Developing country population n = 1864.8; and aortic valve position population n = 2519.4 and mitral valve position population n = 1558.7. On schedule, follow-up to protocol requirements was 91.4% (4224 out of 4620). A consolidated standards of reporting trials flow diagram is provided in Figure E1.
      The preoperative demographic characteristics and risk factors for the total population and the preoperative demographic characteristics and risk factors by aortic and mitral valve positions are detailed elsewhere and are summarized here for convenience.
      • Jamieson W.R.E.
      • Ely J.L.
      • Brink J.
      • Pennel T.
      • Bannon P.
      • Patel J.
      • et al.
      PROSE: Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation: part 1(patient dynamics): preoperative demographics and preoperative and operative risk factors.
      The detailed results are provided in Table E1, Table E10, Table E11, Table E12, Table E13, Table E14, Table E15, Table E16, Table E2, Table E3, Table E4, Table E5, Table E6, Table E7, Table E8, Table E9 and Figure E1, Figure E2, Figure E3.
      The mean age of the total population was 49.0 ± 12.6 years. The gender distribution was 58.8% men. Rheumatic valve etiology was 41.6%, whereas calcific valvular disease was 29.8%. Sinus rhythm was present in 75.2% of patients and atrial fibrillation was present in 23.1% of patients. The mean age for aortic prostheses patients was 52.3 ± 11.4 years. Aortic position patients were 13.7% rheumatic and 46.9% were calcific valve disease. Of the aortic position patients, 92.4% were in sinus rhythm and only 5.6% were in atrial fibrillation. The mean age for mitral position prostheses patients was 44.4 ± 12.8 years. Mitral position patients had 81.7% rheumatic and 5.0% had calcific valve disease. Of the mitral position patients 51.3% were in sinus rhythm and 47.6% were in atrial fibrillation.
      There were no significant differences between On-X and St Jude Medical prosthesis patients for all preoperative and operative risk factors. As expected, the Western and Developing country populations provided the most significant differences for both preoperative and operative demographic characteristics and for preoperative and operative risk factors. All statistically significant (P < .01), preoperative demographic characteristics revealed the patients in the Developing country populations were younger (43.3 ± 12.6 years vs 54.5 ± 9.8 years), predominantly female (54.0% vs 29.0%), predominantly presenting with rheumatic disease (70.1% vs 7.9%), and more frequently in atrial fibrillation (35.6% vs 10.1%). Aortic stenosis was more common in the Western populations (66.5% vs 26.1%), whereas aortic regurgitation was more common in the Developing country populations (27.7% vs 13.0%). Mixed mitral disease was more common in the Developing populations (60.7% vs 32.0%), whereas mitral regurgitation was more common in the Western populations (42.0% vs 15.9%).
      The preoperative and operative risk factors for Western and Developing populations revealed a complete contrast for almost all risk factors with the significant factors predominantly in the Western populations. The comparative risk factors that had statistically significant (P < .01) higher occurrence rates or measured values in the Western world population were coronary artery disease (29.1% vs 4.3%), diabetes mellitus (15.1% vs 7.7%), hypercholesterolemia (44.2% vs 6.7%), preoperative creatinine (98.1 ± 91.0 μmol/L vs 82.9 ± 28.5 μmol/L), hypertension (55.6% vs 20.6%), chronic obstructive pulmonary disease (14.0% vs 4.8%), previous myocardial infarction (8.2% vs 1.2%), and angina pectoris (20.6% vs 6.2%). The aortic valve percentage was more common in the Western population (87.2% vs 29.0%). Intraoperative adverse events were more common in the Western world (12.8% vs 4.8%). Congestive heart failure, on the other hand, was more common in the Developing populations (29.3% vs 21.7%).

      Study Comparison by Prosthesis Type (5-Year Event Rate [% ± SE])

      Kaplan-Meier analysis showed freedom from all-cause mortality was 89.0% to 1.9% for the On-X prosthesis and 90.7% to 1.5% for the St Jude Medical prosthesis (P = .746); valve-related mortality and sudden death was 94.7% to 1.1% for the On-X prosthesis and 95.6% to 1.1% for the St Jude Medical prosthesis (P = .601); TE was 96.8% to 0.9% for the On-X prosthesis and 95.8% to 1.1% for the St Jude Medical prosthesis (P = .606) (Figure 2); and VT was 98.8% to 0.5% for the On-X prosthesis and 98.9% to 0.5% for the St Jude Medical prosthesis (Figure 3). The prosthesis type for aortic and mitral positions was nonsignificant for both life tables and linearized rates for all-cause mortality, valve-related mortality plus sudden death, TE, and VT.
      Figure thumbnail gr2
      Figure 2Freedom from thromboembolism by valve type with 95% CIs. Five-year event-free rate in percent ± SE and log rank P value. On-X Prosthetic Heart Valve (On-X Life Technologies [On-X]/Artivion Inc); St Jude Medical Mechanical Prosthesis (Abbott/St Jude Medical [SJM]). CI, Confidence Interval; SE, standard error.
      Figure thumbnail gr3
      Figure 3Freedom from Valve Thrombosis by Valve Type with 95% CIs. Five-year event-free rate in percent ± SE, and log rank P value. On-X Prosthetic Heart Valve (On-X Life Technologies [On-X]/Artivion Inc); St Jude Medical Mechanical Prosthesis (Abbott/St Jude Medical [SJM]). CI, Confidence interval; SE, standard error.

      Study Comparison by Prosthesis Position (5-Year Event Rate [% ± SE])

      Kaplan-Meier analysis showed freedom from all-cause mortality for the aortic position was 91.2% to 1.3% and for the mitral position was 90.1% to 1.6% (P = .153); valve-related mortality plus sudden death for aortic was 95.4% to 1.0% and for the mitral position was 94.6% to 1.3% (P = .174); TE for aortic was 96.0% to 0.9% and for the mitral position was 96.9% to 1.0% (P = .944); and VT for the aortic position was 96.6% to 0.3% and for the mitral position was 97.8% to 0.8% (P = .0217) (Figure 4).
      Figure thumbnail gr4
      Figure 4Freedom from valve thrombosis by valve position with 95% CIs. Five-year event-free rate in percent ± SE, and log rank P value. CI, Confidence interval; SE, standard error.

      Study Comparison by Economic Development (5-Year Event Rate [% ± SE])

      Kaplan-Meier analysis showed freedom from all-cause mortality for the Developing country population was 88.4% to 1.6% and for the Western population was 92.9% to 1.3% (P = .0055); valve-related mortality and sudden death for the Developing population was 93.3% to 1.3% and for the Western population was 96.8% to 0.9% (P = .0106); TE for the Developing population was 96.1% to 0.7% and for the Western population was 94.7% to 1.1% (P = .0201) (Figure 5); and VT for Developing countries was 97.9% to 0.7% and for the Western population was 99.8% to 0.2% (P = .0137) (Figure 6). The 5-year event rate for Developing and Western populations was nonsignificant for the aortic valve position patients for freedom from all-cause mortality, valve-related mortality and sudden death, TE, and VT.
      Figure thumbnail gr5
      Figure 5Freedom from thromboembolism by site with 95% CIs. Five-year event-free rate in percent ± SE, and log rank P-value. CI, Confidence interval; SE, standard error.
      Figure thumbnail gr6
      Figure 6Freedom from valve thrombosis by site with 95% CI. Five-year event-free rate in percent ± SE, and log rank P value. CI, Confidence interval; SE, standard error.
      The 5-year event rate for Developing and Western populations for mitral valve position patients showed freedom from all-cause mortality for Developing populations was 88.4% to 1.9% and for Western populations was 100.0% to 0.0% (P = .0306); valve-related mortality and sudden death for Developing populations was 93.6% to 1.5% and for Western populations was 100.0% to 0.0% (P = .208); TE for Developing populations was 97.7% to 0.9% and for Western populations was 92.4% to 3.6% (P = .0072): and VT for Developing populations was 97.4% to 1.0% and for Western populations was 100.0% to 0.0% (P = .244).
      The overall risk assessment was conducted for 7 parameters: age, body mass index (BMI), congestive heart failure (CHF), chronic obstructive pulmonary disease, cerebrovascular accident, New York Heart Association (NYHA) functional class, and cardiac rhythm. The significant predictors of all-cause mortality were increases in age, CHF, BMI, NYHA functional class, and CVAs, whereas for valve-related mortality and sudden death there were increases in CHF, BMI, and NYHA functional class. The only predictor of TE in the whole population was increasing age (P <.005, 95% CI 0.05-0.009). VT was predicted by younger age in the whole population (P <.0001, 95% CI 0.15-0.0001), as well as in the Developing country population, both valve prostheses, and both aortic and mitral valve positions. There was no predictor of VT in the Western population due to lack of events.
      The major late hemorrhagic rate for the On-X prosthesis was 1.0% per patient-year (n = 23) and for the St Jude Medical prosthesis was 1.2% per patient-year (n = 23). The major hemorrhagic rates were not differentiated by prostheses overall, by aortic and mitral valve positions, or by economic development. The TE event rates were undifferentiated for the On-X prosthesis at 0.5% per patient-year (n = 12) and for the St Jude Medical prosthesis at 0.5% per patient-year (n = 10). There were TE events in the aortic valve (n = 14) and mitral valve (n = 8) position populations, and in patients in Western (n = 16) and Developing (n = 6) positions. The TE events were more prevalent with aortic versus mitral valve position prostheses, and with aortic valve position in Western versus Developing populations but not the mitral valve position by economic development. Figure 7 shows a breakout of the TE and VT event rates across the various study cohorts. Table E1, Table E10, Table E11, Table E12, Table E13, Table E14, Table E15, Table E16, Table E2, Table E3, Table E4, Table E5, Table E6, Table E7, Table E8, Table E9 show the TE and VT event rates across the various study cohorts for aortic and mitral valve position patients separately.
      Figure thumbnail gr7
      Figure 7Thromboembolism (TE) and valve thrombosis (VT) event rates by study cohort: Summary figure for TE and VT linearized rates in percent per patient-year for all cohorts analyzed with indicators for statistically significant differences at P < .05. Bold double-ended arrows indicate significant differences in VT. SJM, St Jude Medical; On-X, On-X Life Technologies.
      The most prominent major complication was VT (10 events in 9 patients). Within the total population, the On-X prosthesis major complication rate was 0.2% per patient-year (n = 5) and St Jude Medical prosthesis major complication rate was 0.3% per patient-year (n = 5). The aortic valve position major complication rate was 0.1% per patient-year (n = 2) and the mitral valve position major complication rate was 0.5% per patient-year (n = 8) (P = .007). The thrombosis rate was differentiated by economic development: 0.04% per patient-year (n = 1) for the Western population versus 0.5% per patient-year (n = 9) in the Developing country population (P = .005). There were 2 aortic valve positions for the On-X prosthesis (0.1% per patient-year) and 0 in the aortic valve position for the St Jude Medical prosthesis (P = .199). There were 3 mitral valve position prostheses for the On-X (0.4% per patient-year) and 5 mitral valve position St Jude Medical prostheses (0.7% per patient-year) (P = .360). The rate of aortic VT by economic development was 0.05% per patient-year for the Western population (n = 1) and 0.2% per patient-year for the Developing country population (n = 1) (P = .340). Mitral valve thrombosis by economic development was 0 in the Western population, whereas it was 8 in the Developing country population (0.6% per patient-year) (P = .217). One might expect that the occurrence of 0 versus 8 events would be statistically significant, but the lack of mitral patients in the Western population prevents achieving significance here.
      The mean age for prosthesis thrombosis was 28.8 ± 16.0 years, whereas the total population mean age was 45.0 ± 11.5 years. There were a total of 4 St Jude Medical prosthesis cases and 5 On-X prosthesis cases among the initial cases. There were 5 cases treated with thrombolysis, 2 experienced explant surgery, and 1 experienced explant surgery after thrombolysis. There were 2 primary deaths and 1 additional late sudden death. The 2 deaths were due to multisystem failure with shock syndromes. Review of anticoagulant therapy records in all VT patients showed that the INR status varied extensively or was not followed. The time postoperation from the original surgery was mostly relatively early (<1 year) but varied up to 4 years. One of the On-X prosthesis aortic position cases was not receiving anticoagulation therapy at all.
      The postoperative patient status was very satisfactory in the total population, with 77.6% experiencing NYHA functional class improvement and 20.8% experiencing NYHA functional class stability. There was no significant differentiation in postoperative status by prosthesis type, prosthesis position, or economic development status. The cardiac rhythm status in the whole population was atrial fibrillation in 23.1% of patients preoperation and in 9.5% postoperation at 1 year (P < .0001). Similarly, the aortic position population was 5.6% and 2.4% (P = .0002), whereas the mitral valve population was 47.6% and 19.4% (P < .0001). The Western population rates were 10.6% and 5.6% (P < .0001) and in the Developing population 35.5% and 13.6% (P < .0001). In general, improvement in both NYHA functional class and sinus rhythm occurred across the entire trial.

      Discussion

      On-X Prosthesis-Specific Design Features

      As shown in Table 1 and Figure 8, A and C, the On-X prosthesis is a pure pyrolytic carbon prosthesis with a supra-annular sewing ring. The prosthesis design facilitates pannus protection (pannus protection was not a comparative feature of the PROSE trial). The long, flared orifice of the On-X prosthesis facilitates organized flow through the prosthesis (height-to-diameter ratio of about 0.6). The actuated pivots of the On-X prosthesis allow the leaflets to follow the blood flow through the prosthesis. The pivot purge of the On-X prosthesis facilitates the elimination of blood stasis in the prosthesis. The leaflet swing angle through closure is 50°, reducing closing volume and allowing for more pivot purge. The 2-point closure of the On-X prosthesis reduces the impact of leaflet closure.
      Table 1On-X valve (On-X Life Technologies [On-X]/Artivion Inc) versus St Jude Medical valve (St Jude Medical [SJM]) design comparison
      FeatureOn-X valve
      See Figure 8, A and C.
      SJM valve
      See Figure 8, B and D.
      MaterialPure pyrolytic carbonSilicon-alloyed pyrolytic carbon
      Sewing ring positionSupra-annularSupra-annular
      Valve positionIntra–supra-annularSupra-annular
      Pannus overgrowth protectionYesNo
      Orifice lengthLonger natural length-to-diameter ratioShorter less than natural length-to-diameter ratio
      Pivot designActuated by remote center of rotationFixed rotation point
      Leaflet anglesOpen 90°, closed 40°, swing 50°Open 85°, closed 30°, swing 55°
      Leakage pathSmooth through contoured pivot with set gap tolerancesJet through angular pivot
      Closing geometryTwo points at 45° from leaflet tip reducing closing velocitySingle point at tip of leaflet
      See Figure 8, A and C.
      See Figure 8, B and D.
      Figure thumbnail gr8
      Figure 8Prostheses used: A, On-X aortic valve (On-X Life Technologies/Artivion Inc). B, St Jude Medical aortic valve (Abbott/St Jude Medical). C, On-X mitral valve. D, St Jude Medical mitral valve.

      St Jude Medical Prosthesis-Specific Design Features

      As shown in Table 1 and Figure 8, B and D, the St Jude Medical prosthesis is made from a silicon-alloyed pyrolytic carbon that is less strong and more brittle than pure pyrolytic carbon. It also features a supra-annular sewing ring, but its orifice does not extend above and below the ring except at the pivot ears providing little barrier to pannus overgrowth. The height-to-diameter ratio of the housing is approximately 0.3. Its leaflets rotate on a fixed pivot with a leaflet swing of 55° increasing closing volume, thus limiting pivot purge. Its closing contact points are at the tips of the leaflets resulting in a higher likelihood of cavitation.
      Although the results did not bear out the original hypothesis that TE event rates would be significantly lower for the On-X prosthetic valve than for the St Jude Medical prosthetic valve, they do establish that these valves both perform well across the many cohorts in the trial when managed on target anticoagulation levels for both prostheses (aortic prostheses INR, 2.2-2.8 and for mitral prostheses INR, 2.5-3.5). There are many limiting reasons for finding that the historic literature observations are not discovered to hold under a randomized trial, including but not limited to references not being contemporary such that practice can change to improve results, methods of follow-up can be slightly different even using the same event definitions, observer differences are likely, and the variability of results within studies and valves is large enough to mask the small difference being sought. This study attempted to look at these valves under as close to real-world conditions. A brief survey of the literature finds studies for both valves
      • Chan V.
      • Jamieson W.R.E.
      • Lam B.-K.
      • Ruel M.
      • Ling H.
      • Fradet G.
      • et al.
      Influence of the On-X mechanical prosthesis on intermediate-term major thromboembolism and hemorrhage: a prospective multicenter study.
      ,
      • Chambers J.B.
      • Pomar J.L.
      • Mestres C.A.
      • Palatianos G.M.
      Clinical event rates with the On-X bileaflet mechanical heart valve: a multicenter experience with follow-up to 12 years.
      • Baudet E.M.
      • Puel V.
      • McBride J.T.
      • Grimaud J.P.
      • Roques F.
      • Clerc F.
      • et al.
      Surgery for acquired heart disease, long-term results of valve replacement with the St. Jude Medical Prosthesis.
      • Isomura T.
      • Hisatomi K.
      • Hirano A.
      • Kosuga K.
      • Ohishi K.
      The St. Jude medical prosthesis in the mitral position.
      • Remadi J.P.
      • Bizouarn P.
      • Baron O.
      • Habash O.A.
      • Despins P.
      • Michaud J.L.
      • et al.
      Mitral valve replacement with the St. Jude Medical Prosthesis: a 15-year follow-up.
      • Smith J.A.
      • Westlake G.W.
      • Mullerworth M.H.
      • Skillington P.D.
      • Tatoulis J.
      Excellent long-term results of cardiac valve replacement with the St Jude Medical valve prosthesis.
      with rates of TE <1% per patient-year, also conducted under real-world conditions, illustrating the difficulty of establishing small adverse event rate differences, which is a limitation of the study.
      The lack of detailed INR follow-up limits the ability to discern potential effects of varying anticoagulation protocols. However, since this study was completed, a more recent study, Prospective Randomized On-X Anticoagulation Trial (PROACT), has found that for the On-X valve, warfarin anticoagulant therapy can be reduced to create a reduction in bleeding events without increase in thromboembolism for the aortic valve.
      • Puskas J.
      • Gerdisch M.
      • Nichols D.
      • Quinn R.
      • Anderson C.
      • Rhenman B.
      • et al.
      Reduced anticoagulation after mechanical aortic valve replacement: interim results from the Prospective Randomized On-X Valve Anticoagulation Clinical Trial Randomized Food and Drug Administration investigational device exemption trial.
      The currently underway PROACT Xa study (NCT04142658) should also determine whether patients with an On-X mechanical aortic valve can be effectively anticoagulated with apixaban as an alternative to warfarin.
      • Jawitz O.K.
      • Wang T.Y.
      • Lopes R.D.
      • Chavez A.
      • Boyer B.
      • Kim H.
      • et al.
      Rationale and design of PROACT Xa: a randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with an On-X mechanical aortic valve.
      This study allowed a direct comparison of Western and Developing populations but is also limited in comparative power for subset analyses by these same differences. Many of the differences between these 2 populations were assumed to exist based on literature reports, but this trial confirms these assumed differences, such as younger age, rheumatic etiology, mitral versus aortic positions and rates of atrial fibrillation. Unexpectedly, the study also showed that, although TE events increase with age as expected, VT events were associated with younger age. VT events also occurred in patients who had erratic INR results or were simply noncompliant to their therapy.

      Conclusions

      The PROSE trial revealed essentially equal performance for the On-X and St Jude Medical prostheses regarding influence of prosthesis type on major TE, VT, and major hemorrhage, as well as all-cause, valve-related, or unexpected mortality, when managed at target INR levels in the protocol representing standard of care. The only important differentiation occurred with VT occurring in the Developing country populations more than in the Western populations. The mitral thrombosis in the Developing populations occurred in a younger population, identified on multiple logistic regression, possibly due to anticoagulation compliance status because widely variable anticoagulation therapy was consistent in VT patients. The future evaluation of mechanical valve prostheses needs to include extensive randomized evaluation of anticoagulation protocols.

      Webcast

      You can watch a Webcast of this AATS meeting presentation by going to: https://www.aats.org/resources/1318.
      Figure thumbnail fx2

      Conflict of Interest Statement

      On-X Life Technologies (2003-2016)/Artivion Inc (2016 to present) provided reimbursement payments to each center's research department. All other authors reported no conflicts of interest.
      The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.
      The authors thank Alanna Dyck, research coordinator, Division of Cardiovascular Surgery, Department of Surgery, University of British Columbia, British Columbia, Canada, who had responsibility throughout essentially the total length of the Prospective Randomized Trial of the On-X Mechanical Prosthesis and the St Jude Medical Mechanical Prosthesis Evaluation study for the complete study.
      The authors thank all research coordinators at all the study centers who provided extensive support throughout the extended length of the study. ClinicalTrials.gov registration No. NCT000639782.

      Appendix E1

      Table E1Adverse event rates for the whole population
      EventWhole studyOn-X
      On-X Life Technologies/Artivion Inc.
      St Jude Medical
      St Jude Medical.
      P value earlyP value late
      Early
      Values are presented as n (%).
      Late
      Values are presented as n (%/patient-year).
      Early
      Values are presented as n (%).
      N = 462
      Late
      Values are presented as n (%/patient-year).
      ptyr = 2219.8
      Early
      Values are presented as n (%).
      N = 393
      Late
      Values are presented as n (%/patient-year).
      ptyr = 1858.3
      Major bleed28 (3.3)46 (1.1)17 (3.7)23 (1.0)11 (2.8)23 (1.2).462.546
      Cerebrovascular accident5 (0.6)22 (0.5)2 (0.4)12 (0.5)3 (0.8)10 (0.5).444.992
      Peripheral thromboembolism2 (0.05)1 (0.05)1 (0.05).900
      Valve thrombosis10 (0.2)5 (0.2)5 (0.3).778
      Prosthetic endocarditis1 (0.1)7 (0.2)1 (0.2)4 (0.2)2 (0.1).375.547
      Major paravalvular leak1 (0.1)7 (0.2)1 (0.2)6 (0.3)1 (0.05).375.096
      Oversized valve1 (0.1)1 (0.2).375
      Broken leaflet1 (0.1)1 (0.3).239
      Explants4 (0.5)11 (0.3)3 (0.6)7 (0.3)1 (0.3)4 (0.2).519.540
      All mortality22 (2.6)58 (1.4)14 (3.0)31 (1.4)8 (2.0)27 (1.5).355.880
      Valve-related mortality17 (0.4)12 (0.5)5 (0.3).181
      Cardiac mortality8 (0.2)4 (0.2)4 (0.2).801
      Noncardiac mortality15 (0.4)7 (0.3)8 (0.4).546
      Sudden or unknown mortality18 (0.4)8 (0.4)10 (0.5).395
      ptyr, Patient-year.
      On-X Life Technologies/Artivion Inc.
      St Jude Medical.
      Values are presented as n (%).
      § Values are presented as n (%/patient-year).
      Table E2Adverse event rates whole population by position
      EventWhole studyAorticMitralP value earlyP value late
      Early
      Values are presented as n (%).
      Late
      Values are presented as n (%/patient-year).
      Early
      Values are presented as n (%).
      N = 502
      Late
      Values are presented as n (%/patient-year).
      ptyr = 2519.4
      Early
      Values are presented as n (%).
      N = 353
      Late
      Values are presented as n (%/patient-year).
      ptyr = 1558.7
      Major bleed28 (3.3)46 (1.1)18 (3.6)30 (1.2)10 (2.8)16 (1.0).517.631
      Cerebrovascular accident5 (0.6)22 (0.5)2 (0.4)14 (0.6)3 (0.8)8 (0.5).584.858
      Peripheral thromboembolism2 (0.05)2 (0.1).266
      Valve thrombosis10 (0.2)2 (0.1)8 (0.5).007
      Prosthetic endocarditis1 (0.1)7 (0.2)6 (0.2)1 (0.3)1 (0.06).220.192
      Major paravalvular leak1 (0.1)7 (0.2)1 (0.2)4 (0.2)3 (0.2).401.801
      Oversized valve1 (0.1)1 (0.2).401
      Broken leaflet1 (0.1)1 (0.2).401
      Explants4 (0.5)11 (0.3)3 (0.6)8 (0.3)1 (0.3)3 (0.2).531.455
      All mortality22 (2.6)58 (1.4)8 (1.6)35 (1.4)14 (4.0)23 (1.5).030.822
      Valve-related mortality17 (0.4)7 (0.3)10 (0.6).080
      Cardiac mortality8 (0.2)7 (0.3)1 (0.06).134
      Noncardiac mortality15 (0.4)10 (0.4)5 (0.3).697
      Sudden or unknown mortality18 (0.4)11 (0.4)7 (0.5).954
      Bold P values indicate statistical significance. ptyr, Patient-year.
      Values are presented as n (%).
      Values are presented as n (%/patient-year).
      Table E3Adverse event rates for Western versus Developing worlds
      EventWhole studyWesternDevelopingP value earlyP value late
      Early
      Values are presented as n (%).
      Late
      Values are presented as n (%/patient-year).
      Early
      Values are presented as n (%).
      N = 437
      Late
      Values are presented as n (%/patient-year).
      ptyr = 2213.3
      Early
      Values are presented as n (%).
      N = 418
      Late
      Values are presented as n (%/patient-year).
      ptyr = 1864.8
      Major bleed28 (3.3)46 (1.1)18 (4.1)29 (1.3)10 (2.4)17 (0.9).162.232
      Cerebrovascular accident5 (0.6)22 (0.5)4 (0.9)16 (0.7)1 (0.2)6 (0.3).170.082
      Peripheral TE2 (0.05)2 (0.09).194
      Valve thrombosis10 (0.2)1 (0.04)9 (0.5).005
      Prosthetic endocarditis1 (0.1)7 (0.2)1 (0.2)7 (0.3).361.015
      Major paravalvular leak1 (0.1)7 (0.2)4 (0.2)1 (0.2)3 (0.2).879
      Oversized valve1 (0.1)1 (0.2).361
      Broken leaflet1 (0.1)1 (0.2).361
      Explants4 (0.5)11 (0.3)3 (0.7)7 (0.3)1 (0.2)4 (0.2).278.533
      All mortality22 (2.6)58 (1.4)3 (0.7)28 (1.3)19 (4.5)30 (1.6).0004.359
      Valve-related mortality17 (0.4)7 (0.3)10 (0.5).278
      Cardiac mortality8 (0.2)5 (0.2)3 (0.2).640
      Noncardiac mortality15 (0.4)10 (0.5)5 (0.3).335
      Sudden or unknown mortality18 (0.4)6 (0.3)12 (0.6).074
      Bold P values indicate statistical significance. ptyr, Patient-year.
      Values are presented as n (%).
      Values are presented as n (%/patient-year).
      Table E4Adverse event rates for aortic valves by valve type
      EventAortic totalOn-X
      On-X Life Technologies (On-X)/Artivion Inc.
      St Jude Medical
      St Jude Medical.
      P value earlyP value late
      Early
      Values are presented as n (%).
      Late
      Values are presented as n (%/patient-year).
      Early
      St Jude Medical.
      N = 273
      Late
      Values are presented as n (%/patient-year).
      ptyr = 1379.4
      Early
      St Jude Medical.
      N = 229
      Late
      Values are presented as n (%/patient-year).
      ptyr = 1140.0
      Major bleed18 (3.6)30 (1.2)12 (4.4)17 (1.2)6 (2.6)13 (1.1).280.833
      Cerebrovascular accident2 (0.4)14 (0.6)1 (0.4)7 (0.5)1 (0.4)7 (0.6)1.000.721
      Peripheral thromboembolism2 (0.1)1 (0.07)1 (0.1).893
      Valve thrombosis2 (0.1)2 (0.1).199
      Prosthetic endocarditis6 (0.2)4 (0.3)2 (0.2).558
      Major paravalvular leak1 (0.2)4 (0.2)1 (0.4)4 (0.3).338.069
      Oversized valve1 (0.2)1 (0.4).338
      Broken leaflet1 (0.2)1 (0.4).296
      Explants3 (0.6)8 (0.3)2 (0.7)6 (0.4)1 (0.4)2 (0.2).655.250
      All mortality8 (1.6)35 (1.4)6 (2.2)19 (1.4)2 (0.9)16 (1.4).249.956
      Valve-related mortality7 (0.3)6 (0.4)1 (0.1).100
      Cardiac mortality7 (0.3)3 (0.2)4 (0.4).527
      Noncardiac mortality10 (0.4)5 (0.4)5 (0.4).763
      Sudden or unknown mortality11 (0.4)5 (0.4)6 (0.5).536
      ptyr, Patient-year.
      On-X Life Technologies (On-X)/Artivion Inc.
      St Jude Medical.
      Values are presented as n (%).
      § Values are presented as n (%/patient-year).
      Table E5Adverse event rates for mitral valves by valve type
      EventMitral totalOn-X
      On-X Life Technologies (On-X)/Artivion Inc.
      St Jude Medical
      St Jude Medical.
      P value earlyP value late
      Early
      Values are presented as n (%).
      Late
      Values are presented as n (%/patient-year).
      Early
      Values are presented as n (%).
      N = 189
      Late
      Values are presented as n (%/patient-year).
      ptyr = 625.9
      Early
      Values are presented as n (%).
      N = 164
      Late
      Values are presented as n (%/patient-year).
      ptyr = 540.7
      Major bleed10 (2.8)16 (1.0)6 (3.2)6 (0.7)4 (2.4)10 (1.4).652.195
      Cerebrovascular accident3 (0.8)8 (0.5)5 (0.6)3 (1.8)3 (0.4).064.616
      Peripheral thromboembolism
      Valve thrombosis8 (0.5)3 (0.4)5 (0.7).360
      Prosthetic endocarditis1 (0.3)1 (0.06)1 (0.5)1 (0.1).365.282
      Major paravalvular leak3 (0.2)2 (0.2)1 (0.1).651
      Oversized valve
      Broken leaflet
      Explants1 (0.3)3 (0.2)1 (0.5)2 (0.2)1 (0.1).365.651
      All mortality14 (4.0)23 (1.5)8 (4.2)12 (1.4)6 (3.7)11 (1.5).811.887
      Valve-related mortality10 (0.6)6 (0.7)4 (0.6)
      Cardiac mortality1 (0.06)1 (0.1).282
      Noncardiac mortality5 (0.3)3 (0.4)2 (0.3).776
      Sudden or unknown mortality7 (0.5)3 (0.4)4 (0.6).567
      ptyr, Patient-year.
      On-X Life Technologies (On-X)/Artivion Inc.
      St Jude Medical.
      Values are presented as n (%).
      § Values are presented as n (%/patient-year).
      Table E6Adverse event rates for aortic valves by economic development
      EventAortic totalWesternDevelopingP value earlyP value late
      Early
      Values are presented as n (%).
      Late
      Values are presented as n (%/patient-year).
      Early
      Values are presented as n (%).
      N = 381
      Late
      Values are presented as n (%/patient-year).
      ptyr = 1963.7
      Early
      Values are presented as n (%).
      N = 121
      Late
      Values are presented as n (%/patient-year).
      ptyr = 555.7
      Major bleed18 (3.6)30 (1.2)17 (4.5)24 (1.2)1 (0.8)6 (1.1).058.786
      Cerebrovascular accident2 (0.4)14 (0.6)2 (0.5)13 (0.7)1 (0.2).660.178
      Peripheral thromboembolism2 (0.1)2 (0.1).452
      Valve thrombosis2 (0.1)1 (0.05)1 (0.2).340
      Prosthetic endocarditis6 (0.2)6 (0.3).193
      Major paravalvular leak1 (0.2)4 (0.2)1 (0.3)3 (0.2)1 (0.2).547.887
      Oversized valve1 (0.2)1 (0.3).547
      Broken leaflet1 (0.2)1 (0.3).547
      Explants3 (0.6)8 (0.3)3 (0.8)7 (0.4)1 (0.2).324.514
      All mortality8 (1.6)35 (1.4)3 (0.8)27 (1.4)5 (4.1)8 (1.4).012.909
      Valve-related mortality7 (0.3)6 (0.3)1 (0.2).620
      Cardiac mortality7 (0.3)6 (0.3)1 (0.2).620
      Noncardiac mortality10 (0.4)8 (0.4)2 (0.4).875
      Sudden or unknown mortality11 (0.4)7 (0.4)4 (0.7).252
      Bold P values indicate statistical significance. ptyr, Patient-year.
      Values are presented as n (%).
      Values are presented as n (%/patient-year).
      Table E7Adverse event rates for mitral valves by economic development
      EventMitral totalWesternDevelopingP value earlyP value late
      Early
      Values are presented as n (%).
      Late
      Values are presented as n (%/patient-year).
      Early
      Values are presented as n (%).
      N = 56
      Late
      Values are presented as n (%/patient-year).
      ptyr = 249.6
      Early
      Values are presented as n (%).
      N = 297
      Late
      Values are presented as n (%/patient-year).
      ptyr = 1309.1
      Major bleed10 (2.8)16 (1.0)1 (1.8)6 (2.4)9 (3.0)11 (0.8).619.030
      Cerebrovascular accident3 (0.8)8 (0.5)1 (1.8)3 (1.2)1 (0.3)5 (0.4).160.098
      Peripheral thromboembolism
      Valve thrombosis8 (0.5)08 (0.6).217
      Prosthetic endocarditis1 (0.3)1 (0.06)1 (1.8)1 (0.4)00.021.022
      Major paravalvular leak3 (0.2)1 (0.4)2 (0.2).413
      Oversized valve
      Broken leaflet
      Explants1 (0.3)3 (0.2)1 (1.8)003 (0.2).021.450
      All mortality14 (4.0)23 (1.5)01 (0.4)14 (4.7)22 (1.7).003.127
      Valve-related mortality10 (0.6)1 (0.4)9 (0.7).604
      Cardiac mortality1 (0.06)01 (0.08).662
      Noncardiac mortality5 (0.3)05 (0.4).329
      Sudden or unknown mortality7 (0.5)07 (0.5).248
      Bold P values indicate statistical significance. ptyr, Patient-year.
      Values are presented as n (%).
      Values are presented as n (%/patient-year).
      Table E8New York Heart Association functional class cross-tabulation: Preoperation (Preop) to 1-year postoperation (Postop) for the whole cohort
      PostopPreopIIIIIIIVTotal
      I5660062
      II2124041257
      III19276430311
      IV19154038
      Total479137511668
      Percent improved77.6
      Percent stable20.8
      Percent worsened1.6
      Table E9New York Heart Association functional class cross-tabulation: Preoperation (Preop) to 1-year postoperation (Postop) for On-X (On-X Life Technologies/Artivion Inc) patients
      PostopPreopIIIIIIIVTotal
      I3330036
      II1121821133
      III10542190166
      IV22102034
      Total27273231369
      Percent improved79.4
      Percent stable19.0
      Percent worsened1.6
      Table E10New York Heart Association functional class cross-tabulation: Preoperation (Preop) to 1-year postoperation (Postop) for St Jude Medical patients
      PostopPreopIIIIIIIVTotal
      I2330026
      II1002220124
      III8734240145
      IV1952026
      Total22964280321
      Percent improved76.9
      Percent stable21.5
      Percent worsened1.6
      Table E11New York Heart Association functional class cross-tabulation: Preoperation (Preop) to 1-year postoperation (Postop) for aortic patients
      PostopPreopIIIIIIIVTotal
      I5250057
      II1412111164
      III11032200162
      IV2293034
      Total32567241417
      Percent improved77.9
      Percent stable22.3
      Percent worsened1.7
      Table E12New York Heart Association functional class cross-tabulation: Preoperation (Preop) to 1-year postoperation (Postop) for mitral patients
      PostopPreopIIIIIIIVTotal
      I41005
      II71193093
      III8244230149
      IV1961026
      Total17670270273
      Percent improved81.7
      Percent stable16.8
      Percent worsened1.5
      Table E13New York Heart Association functional class cross-tabulation: Preoperation (Preop) to 1-year postoperation (Postop) for the Western population
      PostopPreopIIIIIIIVTotal
      I5350058
      II1311011143
      III10521130139
      IV24114039
      Total31347181379
      Percent improved78.1
      Percent stable20.1
      Percent worsened1.8
      Table E14New York Heart Association functional class cross-tabulation: Preoperation (Preop) to 1-year postoperation (Postop) for the developing population
      PostopPreopIIIIIIIVTotal
      I31004
      II813030114
      III8755300172
      IV1740021
      Total18890330311
      Percent improved78.5
      Percent stable20.3
      Percent worsened1.3
      Table E15Preoperative (Preop) and 1-year postoperative (Postop) cardiac rhythm
      Patient groupSinusAtrial fibrillationPacedOtherP value for postop improvement
      Whole cohort
       Preop627 (75.2)193 (23.1)3 (0.4)11 (1.3)
       Postop578 (87.4)63 (9.5)19 (2.9)1 (0.2)<.0001
      On-X
      On-X Life Technologies (On-X)/Artivion Inc.
       Preop338 (75.1)105 (23.3)1 (0.2)6 (1.3)
       Postop327 (88.9)30 (8.2)11 (3.0)0 (0.0)<.0001
      St Jude Medical
      Abbott/St Jude Medical.
       Preop289 (75.3)88 (22.9)2 (0.5)5 (1.3)
       Postop251 (85.7)33 (11.3)8 (2.7)1 (0.3).0001
      Aortic
       Preop448 (92.4)27 (5.6)3 (0.6)7 (1.4)
       Postop360 (94.2)9 (2.4)13 (3.4)0 (0.0).0002
      Mitral
       Preop179 (51.3)166 (47.6)0 (0.0)4 (1.1)
       Postop218 (78.1)54 (19.4)6 (2.2)1 (0.4)<.0001
      Western
       Preop364 (87.5)44 (10.6)1 (0.2)7 (1.7)
       Postop303 (89.9)19 (5.6)15 (4.5)0 (0.0)<.0001
      Developing
       Preop263 (62.9)149 (35.6)2 (0.5)4 (1.0)
       Postop275 (84.9)44 (13.6)4 (1.2)1 (0.3)<.0001
      Values are presented as n (%). Bold P values indicate statistical significance.
      On-X Life Technologies (On-X)/Artivion Inc.
      Abbott/St Jude Medical.
      Table E16Multiple logistic regression modeling results
      GroupEvent
      Values are presented as model P value, factor(s) coefficient P value.
      All-cause mortalityValve-related plus sudden deathTEVTThrombotic events
      Whole<.0001, congestive HF, .97 to .0001, NYHA, .64 to .016.0005, congestive HF, 1.01 to .003, NYHA, .84 to .027.005, age, .05 to .009<.0001, age, –.15 to .0001 inverse to ageNo relationships
      Developing<.0001, age .03 - .029, congestive HF 1.25 – .0001.01, congestive HF 1.06 – 0.01No relationships.0001, age -0.13, .002 inverse to ageNo relationships
      Western.0001, BMI, .08 to .0008, CVA, 1.43 to .044, NYHA, .95 to .33.001, BMI, .11 to .0006No relationshipsNo relationships (only 1 event)No relationships
      On-X
      On-X Life Technologies/Artivion Inc.
      .007, BMI, .038 to .048, NYHA, .87 –.018.009, congestive HF, 1.17 to .008No relationships.0001, age, –.15 to .002 inverse to ageNo relationships
      St Jude Medical
      Abbott/St Jude Medical.
      .0006, congestive HF, 1.28 to .0005No relationships.005, age, .08 to .013.017, age, –.10 to .03 inverse to age.03, NYHA, 1.15 to .046
      Aortic<.0001, BMI, .07 to .0005, CVA, 1.38 to .017, congestive HF, .93 to .010.0004, BMI, .08 to .004, congestive HF, 1.29 to .008No relationships.027, age, –.12 to .043 inverse to ageNo relationships
      Mitral.010, congestive HF, 0.93 to .010No relationships.01, age .06 to .016.0004, age –0.12 to .003 inverse to ageNo relationships
      TE, Thromboembolism. VT, valve thrombosis; HF, heart failure; NYHA, New York Heart Association functional class; BMI, body mass index; CVA, cardiovascular accident.
      Values are presented as model P value, factor(s) coefficient P value.
      On-X Life Technologies/Artivion Inc.
      Abbott/St Jude Medical.
      Figure thumbnail fx3
      Figure E1Consolidated standards of reporting trials flow diagram for randomized groups in the Prospective Randomized On-X Prosthesis Versus St Jude Medical Mechanical Prosthesis Evaluation trial.
      Figure thumbnail fx4
      Figure E2Thromboembolism (TE) and valve thrombosis (VT) rates for mitral patients by cohort. Summary figure for TE and VT linearized rates among mitral valve patients in percent per patient-year for all cohorts analyzed with indicators for statistically significant differences at P < .05. On-X, On-X Life Technologies; SJM, St Jude Medical.
      Figure thumbnail fx5
      Figure E3Thromboembolism (TE) and valve thrombosis (VT) rates for aortic patients by cohort. Summary figure for TE and VT linearized rates among aortic valve patients in percent per patient-year for all cohorts analyzed with indicators for statistically significant differences at P < .05. On-X, On-X Life Technologies; SJM, St Jude Medical.

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