Online Appendix for the following December 17 JACC article
TITLE: The Optimal Intensity of Vitamin K Antagonists IN Patients With Mechanical Heart
Valves: A Meta-Analysis
AUTHORS: Roel Vink, MD, Department of Vascular Medicine, Roderik A. Kraaijenhagen, MD,
Department of Cardiology, Barbara A. Hutten, PhD, Department of Clinical Epidemiology and
Biostatistics, Renee B. A. van den Brink, MD, Department of Cardiology, Bas A. de Mol, MD,
Department of Cardiopulmonary Surgery, Harry R. Büller, MD, Department of Vascular Medicine,
Marcel Levi, MD, Department of Vascular Medicine, Academic Medical Center, University of
Amsterdam, Amsterdam, The Netherlands
APPENDIX
To follow are a list of excluded articles: inability to differentiate between aortic and mitral valves
(123); intensity of oral anticoagulant therapy was not specified (2450); the events or patient-years
were not specified (5168); the use of antiplatelet therapy (6982); the cohort was the same as another
included study (8390); lost to follow-up not specified or exceeding 5% (9196); and other reasons
(97106).
References
1. Acar J, Iung B, Boissel JP, et al. AREVA: multicenter randomized comparison of low-dose versus
standard-dose anticoagulation in patients with mechanical prosthetic heart valves. Circulation
1996;94:210712.
2. Akins CW, Hilgenberg AD, Buckley MJ, et al. Mitral valve reconstruction versus replacement for
degenerative or ischemic mitral regurgitation. Ann Thorac Surg 1994; 58:66875.
3. Altman R, Rouvier J, Gurfinkel E, et al. Comparison of two levels of anticoagulant therapy in patients
with substitute heart valves. J Thorac Cardiovasc Surg 1991;101:42731.
4. Altman R, Rouvier J, Gurfinkel E, et al. Comparison of high-dose with low-dose aspirin in patients
with mechanical heart valve replacement treated with oral anticoagulant. Circulation 1996;94:21136.
5. Antunes MJ. Clinical performance of St. Jude and Medtronic-Hall prostheses: a randomized
comparative study. Ann Thorac Surg 1990;50:7437.
6. Aris A, Padro JM, Camara ML et al. The Monostrut Bjork-Shiley valve. Seven years’ experience. J
Thorac Cardiovasc Surg 1992;103:107482.
7. Callaghan JC, Teijeira FJ, Bonneau D, et al. A five year study of the incidence of valve-related
complications with the Omniscience cardiac prosthesis. J Cardiovasc Surg (Torino) 1986;27:5002.
8. Chang BC, Lim SH, Kim DK, et al. Long-term results with St. Jude Medical and CarboMedics
prosthetic heart valves. J Heart Valve Dis 2001;10:18594.
9. Chesebro JH, Fuster V, Elveback LR, et al. Trial of combined warfarin plus dipyridamole or aspirin
therapy in prosthetic heart valve replacement: danger of aspirin compared with dipyridamole. Am J
Cardiol 1983;51:153741.
10. Fernandez J, Laub GW, Adkins MS, et al. Early and late-phase events after valve replacement with
the St. Jude Medical prosthesis in 1,200 patients. J Thorac Cardiovasc Surg 1994;107:394406.
11. Hammermeister K, Sethi GK, Henderson WG, et al. 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8.
12. Hammond GL, Geha AS, Kopf GS, et al. Biological versus mechanical valves. Analysis of 1,116
valves inserted in 1,012 adult patients with a 4,818 patient-year and a 5,327 valve-year follow-up. J
Thorac Cardiovasc Surg 1987;93:18298.
13. Klepetko W, Moritz A, Khunl-Brady G, et al. Implantation of the Duromedics bileaflet cardiac valve
prosthesis in 400 patients. Ann Thorac Surg 1987;44:3039.
14. Kontozis L, Skudicky D, Hopley MJ, et al. Long-term follow-up of St. Jude Medical prosthesis in a
young rheumatic population using low-level warfarin anticoagulation: an analysis of the temporal
distribution of causes of death. Am J Cardiol 1998;81:7369.
15. Kopf GS, Hammond GL, Geha AS, et al. Long-term performance of the St. Jude Medical valve: low
incidence of thromboembolism and hemorrhagic complications with modest doses of warfarin.
Circulation 1987; 76:III1326.
16. Kuntze CE, Ebels T, Eijgelaar A, et al. Rates of thromboembolism with three different mechanical
heart valve prostheses: randomised study. Lancet 1989;1:5147.
17. Rosengart TK, O’Hara M, Lang SJ et al. Outcome analysis of 245 CarboMedics and St. Jude valves
implanted at the same institution. Ann Thorac Surg 1998; 66:1684-1691.
18. Saour JN, Sieck JO, Mamo LA, et al. Trial of different intensities of anticoagulation in patients with
prosthetic heart valves. N Engl J Med 1990;322:42832.
19. Skudicky D, Essop MR, Wisenbaugh T, et al. Frequency of prosthetic valve-related complications
with very low level warfarin anticoagulation combined with dipyridamole after valve replacement using
St. Jude Medical prostheses. Am J Cardiol 1994;74:113741.
20. Sullivan JM, Harken DE, Gorlin R. Pharmacologic control of thromboembolic complications of
cardiac-valve replacement. N Engl J Med 1971;284:13914.
21. Turpie AG, Gent M, Laupacis A, et al. A comparison of aspirin with placebo in patients treated with
warfarin after heart-valve replacement. N Engl J Med 1993;329:5249.
22. Vogt S, Hoffmann A, Roth J, et al. Heart valve replacement with the Bjork-Shiley and St Jude
Medical prostheses: a randomized comparison in 178 patients. Eur Heart J 1990;11:58391.
23. Wang SS, Chu SH, Tsai CH, et al. Clinical use of CarboMedics and St. Jude Medical valves. Artif
Organs 1996;20:1299303.
24. Antunes MJ, Wessels A, Sadowski RG, et al. Medtronic Hall valve replacement in a third-world
population group. A review of the performance of 1000 prostheses. J Thorac Cardiovasc Surg
1988;95:98093.
25. Baudet E, Roques X, McBride J, et al. A 8-year follow-up of the Edwards-Duromedics bileaflet
prosthesis. J Cardiovasc Surg (Torino) 1995;36:43742.
26. Bernal JM, Rabasa JM, Gutierrez-Garcia F, et al. The CarboMedics valve: experience with 1,049
implants. Ann Thorac Surg 1998;65:13743.
27. Borkon AM, Soule L, Baughman KL, et al. Ten-year analysis of the Bjork-Shiley standard aortic
valve. Ann Thorac Surg 1987;43:3951.
28. Burckhardt D, Striebel D, Vogt S, et al. Heart valve replacement with St. Jude Medical valve
prosthesis. Long-term experience in 743 patients in Switzerland. Circulation 1988;78:I1824.
29. Carrier M, Martineau JP, Bonan R, et al. Clinical and hemodynamic assessment of the Omniscience
prosthetic heart valve. J Thorac Cardiovasc Surg 1987;93:3007.
30. Carrier M, Pellerin M, Perrault LP, et al. Aortic valve replacement with mechanical and biologic
prosthesis in middle-aged patients. Ann Thorac Surg 2001;71:S2536.
31. Cen YY, Glower DD, Landolfo K, et al. Comparison of survival after mitral valve replacement with
biologic and mechanical valves in 1,139 patients. J Thorac Cardiovasc Surg 2001;122:56977.
32. Chaux A, Czer LS, Matloff JM, et al. The St. Jude Medical bileaflet valve prosthesis. A 5 year
experience. J Thorac Cardiovasc Surg 1984;88:70617.
33. Copeland JG III, Sethi GK. Four-year experience with the CarboMedics valve: the North American
experience. North American team of clinical investigators for the CarboMedics prosthetic heart valve.
Ann Thorac Surg 1994;58:6307.
34. Daenen W, Van Kerrebroeck C, Stalpaert G et al. The Bjork-Shiley Monostrut valve. Clinical
experience in 647 patients. J Thorac Cardiovasc Surg 1993;106:91827.
35. DeWall R, Pelletier LC, Panebianco A, et al. Five-year clinical experience with the Omniscience
cardiac valve. Ann Thorac Surg 1984;38:27580.
36. Douglas PS, Hirshfeld JW Jr., Edie RN et al. Clinical comparison of St. Jude and porcine aortic
valve prostheses. Circulation 1985;72:II1359.
37. He GW, Grunkemeier GL, Gately HL, et al. Up to thirty-year survival after aortic valve replacement
in the small aortic root. Ann Thorac Surg 1995;59:105662.
38. Jamieson WR, Fradet GJ, Miyagishima RT, et al. CarboMedics mechanical prosthesis: performance
at eight years. J Heart Valve Dis 2000;9:67887.
39. Kallewaard M, Algra A, Defauw J, et al. Long-term survival after valve replacement with BjorkShiley CC valves. Bjork-Shiley Study Group. Am J Cardiol 2000;85:598603.
40. Katircioglu SF, Yamak B, Ulus AT, et al. Aortic valve replacement with the St. Jude Medical
prosthesis and fixed dose anticoagulation. J Card Surg 1997;12:36370.
41. Katircioglu SF, Yamak B, Ulus AT, et al. Mitral valve replacement with St. Jude Medical prosthesis
and low-dose anticoagulation in patients aged over 50 years. J Heart Valve Dis 1998;7:4559.
42. Katircioglu SF, Yamak B, Ulus AT, et al. Comparison of 21-23 size St. Jude medical valves to the
27-29 size mechanical valves in aortic position. Ten-year follow-up. J Cardiovasc Surg (Torino)
2000;41:316.
43. Li HH, Hahn J, Urbanski P, et al. Intermediate-term results with 1,019 carbomedics aortic valves.
Ann Thorac Surg 2001;71:11817.
44. Myers ML, Lawrie GM, Crawford ES, et al. The St. Jude valve prosthesis: analysis of the clinical
results in 815 implants and the need for systemic anticoagulation. J Am Coll Cardiol 1989;13:5762.
45. Orszulak TA, Schaff HV, DeSmet JM, et al. Late results of valve replacement with the Bjork-Shiley
valve (1973 to 1982). J Thorac Cardiovasc Surg 1993;105:30212.
46. Rabago G, Martinell J, Fraile J, et al. Results and complications with the Omniscience prosthesis. J
Thorac Cardiovasc Surg 1984;87:13640.
47. Sawant D, Singh AK, Feng WC, et al. St. Jude Medical cardiac valves in small aortic roots: followup to sixteen years. J Thorac Cardiovasc Surg 1997;113:499509.
48. Stewart S, Cianciotta D, Hicks GL, et al. The Lillehei-Kaster aortic valve prosthesis. Long-term
results in 273 patients with 1253 patient-years of follow-up. J Thorac Cardiovasc Surg
1988;95:102330.
49. Yamak B, Karagoz HY, Zorlutuna Y, et al. Low-dose anticoagulant management of patients with St.
Jude Medical mechanical valve prostheses. Thorac Cardiovasc Surg 1993;41:3842.
50. Yamak B, Iscan Z, Mavitas B, et al. Low-dose oral anticoagulation and antiplatelet therapy with St.
Jude Medical heart valve prosthesis. J Heart Valve Dis 1999;8:66573.
51. Akalin H, Corapcioglu ET, Ozyurda U, et al. Clinical evaluation of the Omniscience cardiac valve
prosthesis. Follow-up of up to 6 years. J Thorac Cardiovasc Surg 1992;103:25966.
52. Autschbach R, Walther T, Falk V, et al. Prospectively randomized comparison of different
mechanical aortic valves. Circulation 2000;102:III14.
53. Bloomfield P, Wheatley DJ, Prescott RJ, et al. Twelve-year comparison of a Bjork-Shiley
mechanical heart valve with porcine bioprostheses. N Engl J Med 1991; 324:5739.
54. Casselman F, Herijgers P, Meyns B, et al. The Bicarbon heart valve prosthesis: short-term results. J
Heart Valve Dis 1997;6:4105.
55. de Luca L, Vitale N, Giannolo B, et al. Mid-term follow-up after heart valve replacement with
CarboMedics bileaflet prostheses. J Thorac Cardiovasc Surg 1993;106:115865.
56. Demirag M, Kirali K, Omeroglu SN, et al. Mechanical versus biological valve prosthesis in the
mitral position: a 10-year follow up of St. Jude Medical and Biocor valves. J Heart Valve Dis
2001;10:7883.
57. Fananapazir L, Clarke DB, Dark JF, et al. Results of valve replacement with the Omniscience
prosthesis. J Thorac Cardiovasc Surg 1983;86:6215.
58. Gossinger H, Niessner H, Grubeck B, et al. Thromboembolism in patients with prosthetic heart
valves. An adequately controlled intense anticoagulant therapy and its influence on the occurrence of
thromboembolism in relation to valve type. Thorac Cardiovasc Surg 1986;34:2836.
59. Kazui T, Yamada O, Yamagishi M, et al. Aortic valve replacement with omniscience and
omnicarbon valves. Ann Thorac Surg 1991;52:23643.
60. Keenan RJ, Armitage JM, Trento A, et al. Clinical experience with the Medtronic-Hall valve
prosthesis. Ann Thorac Surg 1990;50:74853.
61. Kvidal P, Bergstrom R, Horte LG, et al. Observed and relative survival after aortic valve
replacement. J Am Coll Cardiol 2000;35:74756.
62. Montero CG, Rufilanchas JJ, Juffe A, et al. Long-term results of cardiac valve replacement with the
Delrin-disc model of the Bjork-Shiley valve prosthesis. Ann Thorac Surg 1984;37:32836.
63. Pengo V, Barbero F, Banzato A, et al. A comparison of a moderate with moderate-high intensity oral
anticoagulant treatment in patients with mechanical heart valve prostheses. Thromb Haemost
1997;77:83944.
64. Remadi JP, Bizouarn P, Baron O, et al. Mitral valve replacement with the St. Jude Medical
prosthesis: a 15-year follow-up. Ann Thorac Surg 1998;66:7627.
65. Rodler SM, Moritz A, Schreiner W, et al. Five-year follow-up after heart valve replacement with the
CarboMedics bileaflet prosthesis. Ann Thorac Surg 1997;63:101825.
66. Sidhu P, O’Kane HO. Self-managed anticoagulation: results from a two-year prospective
randomized trial with heart valve patients. Ann Thorac Surg 2001;72:15237.
67. Vallejo JL, Gonzalez-Santos JM, Albertos J, et al. Eight years’ experience with the Medtronic-Hall
valve prosthesis. Ann Thorac Surg 1990; 50:42936.
68. Wilson DB, Dunn MI, Hassanein K. Low-intensity anticoagulation in mechanical cardiac prosthetic
valves. Chest 1991;100:15537.
69. Abe T, Kamata K, Kuwaki K, et al. Ten years’ experience of aortic valve replacement with the
Omnicarbon valve prosthesis. Ann Thorac Surg 1996;61:11827.
70. Aoyagi S, Oryoji A, Nishi Y, et al. Long-term results of valve replacement with the St. Jude Medical
valve. J Thorac Cardiovasc Surg 1994;108:10219.
71. Butchart EG, Li HH, Payne N, et al. Twenty years’ experience with the Medtronic Hall valve. J
Thorac Cardiovasc Surg 2001;121:1090100.
72. Calkavur T, Yagdi T, Apaydin A, et al. Four years’ experience with the Edwards-Tekna bileaflet
valve prosthesis. J Heart Valve Dis 2002;11:2639.
73. Czer LS, Chaux A, Matloff JM, et al. Ten-year experience with the St. Jude Medical valve for
primary valve replacement. J Thorac Cardiovasc Surg 1990;100:4454.
74. Ibrahim M, O’Kane H, Cleland J, et al. The St. Jude Medical prosthesis. A thirteen-year experience.
J Thorac Cardiovasc Surg 1994;108:22130.
75. Iguro Y, Moriyama Y, Yamaoka A, et al. Clinical experience of 473 patients with the omnicarbon
prosthetic heart valve. J Heart Valve Dis 1999;8:6749.
76. Isomura T, Hisatomi K, Hirano A, et al. The St. Jude medical prosthesis in the mitral position. Eur J
Cardiothorac Surg 1994;8:114.
77. Kuntze CE, Blackstone EH, Ebels T. Thromboembolism and mechanical heart valves: a randomized
study revisited. Ann Thorac Surg 1998;66:1017.
78. Nair CK, Mohiuddin SM, Hilleman DE, et al. Ten-year results with the St. Jude Medical prosthesis.
Am J Cardiol 1990;65:21725.
79. Peterseim DS, Cen YY, Cheruvu S, et al. Long-term outcome after biologic versus mechanical aortic
valve replacement in 841 patients. J Thorac Cardiovasc Surg 1999;117:8907.
80. Santini F, Casali G, Viscardi F, et al. The CarboMedics prosthetic heart valve: experience with 1,084
implants. J Heart Valve Dis 2002;11:1216.
81. Sinci V, Halit V, Kalaycioglu S, et al. Eight year experience with the CarboMedics bileaflet valvular
prosthesis. Ann Thorac Cardiovasc Surg 1999;5:3826.
82. Soga Y, Okabayashi H, Nishina T, et al. Up to 8-year follow-up of valve replacement with
carbomedics valve. Ann Thorac Surg 2002;73:4749.
83. Crawford FA Jr., Kratz JM, Sade RM, et al. Aortic and mitral valve replacement with the St. Jude
Medical prosthesis. Ann Surg 1984;199:75361.
84. Fiane AE, Saatvedt K, Svennevig JL, et al. The CarboMedics valve: midterm follow-up with
analysis of risk factors. Ann Thorac Surg 1995;60:10538.
85. Fiore AC, Naunheim KS, D’Orazio S, et al. Mitral valve replacement: randomized trial of St. Jude
and Medtronic-Hall prostheses. Ann Thorac Surg 1992;54:6873.
86. Hall KV, Nitter-Hauge S, Abdelnoor M. Seven and one-half years’ experience with the MedtronicHall valve. J Am Coll Cardiol 1985;6:141721.
87. Khan S, Chaux A, Matloff J, et al. The St. Jude Medical valve. Experience with 1,000 cases. J
Thorac Cardiovasc Surg 1994;108:10109.
88. Kratz JM, Crawford FA Jr., Sade RM, et al. St. Jude prosthesis for aortic and mitral valve
replacement: a ten-year experience. Ann Thorac Surg 1993;56:4628.
89. Moritz A, Klepetko W, Rodler S, et al. Six-year follow-up after heart valve replacement with the
Edwards Duromedics bileaflet prosthesis. Eur J Cardiothorac Surg 1993;7:8490.
90. Nitter-Hauge S, Abdelnoor M. Ten-year experience with the Medtronic Hall valvular prosthesis. A
study of 1,104 patients. Circulation 1989;80:I438.
91. Arom KV, Nicoloff DM, Kersten TE, et al. Ten years’ experience with the St. Jude Medical valve
prosthesis. Ann Thorac Surg 1989;47:8317.
92. Cortina JM, Martinell J, Artiz V, et al. Comparative clinical results with Omniscience (STM1),
Medtronic-Hall, and Bjork-Shiley convexo-concave (70 degrees) prostheses in mitral valve replacement.
J Thorac Cardiovasc Surg 1986;91:17483.
93. Daenen W, Nevelsteen A, van Cauwelaert P, et al. Nine years’ experience with the Bjork-Shiley
prosthetic valve: early and late results of 932 valve replacements. Ann Thorac Surg 1983;35:65163.
94. Duncan JM, Cooley DA, Reul GJ, et al. Durability and low thrombogenicity of the St. Jude Medical
valve at 5-year follow-up. Ann Thorac Surg 1986;42:5005.
95. Masters RG, Helou J, Pipe AL, et al. Comparative clinical outcomes with St. Jude Medical,
Medtronic Hall and CarboMedics mechanical heart valves. J Heart Valve Dis 2001;10:4039.
96. Vitale N, Giannolo B, Nappi GA, et al. Long-term follow-up of different models of mechanical and
biological mitral prostheses. Eur J Cardiothorac Surg 1995;9:1819.
97. Casselman FP, Bots ML, Van Lommel W, et al. Repeated thromboembolic and bleeding events after
mechanical aortic valve replacement. Ann Thorac Surg 2001;71:117280.
98. Dale J. Arterial thromboembolic complications in patients with Bjork-Shiley and Lillehei-Kaster
aortic disc valve prostheses. Am Heart J 1977;93:71522.
99. DiSesa VJ, Collins JJ Jr., Cohn LH. Hematological complications with the St. Jude valve and
reduced-dose Coumadin. Ann Thorac Surg 1989;48:2803.
100. Hartz RS, LoCicero J III, Kucich V et al. Comparative study of warfarin versus antiplatelet therapy
in patients with a St. Jude Medical valve in the aortic position. J Thorac Cardiovasc Surg
1986;92:68490.
101. Hassouna A, Allam H, Awad A,et al. Standard versus low-level anticoagulation combined to lowdose dipyridamole after mitral valve replacement. Cardiovasc Surg 2000;8:4918.
102. Horstkotte D, Korfer R, Seipel L, et al. Late complications in patients with Bjork-Shiley and St.
Jude Medical heart valve replacement. Circulation 1983;68:II17584.
103. Horstkotte D, Schulte HD, Bircks W, et al. Lower intensity anticoagulation therapy results in lower
complication rates with the St. Jude Medical prosthesis. J Thorac Cardiovasc Surg 1994;107:113645.
104. Meschengieser SS, Fondevila CG, Frontroth J, et al. Low-intensity oral anticoagulation plus lowdose aspirin versus high-intensity oral anticoagulation alone: a randomized trial in patients with
mechanical prosthetic heart valves. J Thorac Cardiovasc Surg 1997;113:9106.
105. Misawa Y, Hasegawa T, Kato M. Clinical experience with the Omnicarbon prosthetic heart valve. J
Thorac Cardiovasc Surg 1993;105:16872.
106. Mok CK, Boey J, Wang R, et al. Warfarin versus dipyridamole-aspirin and pentoxifylline-aspirin
for the prevention of prosthetic heart valve thromboembolism: a prospective randomized clinical trial.
Circulation 1985;72:105963.