10 Aptamers for Thrombotic Diseases
315
patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
(Writing Committee to Revise the 2002 Guidelines for the Management of Patients With
Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with
the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American
Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic
Emergency Medicine. J Am Coll Cardiol 50(7):e1–e157
69. Vavalle JP, Cohen MG (2012) The REG1 anticoagulation system: a novel actively controlled
factor IX inhibitor using RNA aptamer technology for treatment of acute coronary syndrome.
Future Cardiol 8(3):371–382
70. Rao SV, Jollis JG, Harrington RA, Granger CB, Newby LK, Armstrong PW, Moliterno
DJ, Lindblad L, Pieper K, Topol EJ, Stamler JS, Califf RM (2004) Relationship of
blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA
292(13):1555–1562
71. Szlam F, Luan D, Bolliger D, Szlam AD, Levy JH, Varner JD, Tanaka KA (2010) Antifactor IXa Aptamer reduces propagation of thrombin generation in plasma anticoagulated
with warfarin. Thromb Res 125(5):432–437
72. Smith SB, Gailani D (2008) Update on the physiology and pathology of factor IX activation
by factor XIa. Expert Rev Hematol 1(1):87–98
73. Schmidt AE, Bajaj SP (2003) Structure-function relationships in factor IX and factor IXa.
Trends Cardiovasc Med 13(1):39–45
74. Rusconi CP, Roberts JD, Pitoc GA, Nimjee SM, White RR, Quick G, Scardino E, Fay WP,
Sullenger BA (2004) Antidote-mediated control of an anticoagulant aptamer in vivo. Nat
Biotechnol 22(11):1423–1428
75. Rusconi CP, Scardino E, Layzer J, Pitoc GA, Ortel TL, Monroe D, Sullenger BA (2002) RNA
aptamers as reversible antagonists of coagulation factor IXa. Nature 419(6902):90–94
76. Nimjee SM, Keys JR, Pitoc GA, Quick G, Rusconi CP, Sullenger BA (2006) A novel antidotecontrolled anticoagulant reduces thrombin generation and inflammation and improves cardiac
function in cardiopulmonary bypass surgery. Mol Ther 14(3):408–415
77. Dyke CK, Steinhubl SR, Kleiman NS, Cannon RO, Aberle LG, Lin M, Myles SK, Melloni C,
Harrington RA, Alexander JA, Becker RC, Rusconi CP (2006) First-in-human experience of
an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity.
Circulation 114(23):2490–2497
78. Povsic TJ, Vavalle JP, Aberle LH, Kasprzak JD, Cohen MG, Mehran R, Bode C, Buller
CE, Montalescot G, Cornel JH, Rynkiewicz A, Ring ME, Zeymer U, Natarajan M, Delarche
N, Zelenkofske SL, Becker RC, Alexander JH, Investigators RADAR (2013) A Phase 2,
randomized, partially blinded, active-controlled study assessing the efficacy and safety of
variable anticoagulation reversal using the REG1 system in patients with acute coronary
syndromes: results of the RADAR trial. Eur Heart J 34(31):2481–2489
79. Chan MY, Cohen MG, Dyke CK, Myles SK, Aberle LG, Lin M, Walder J, Steinhubl SR,
Gilchrist IC, Kleiman NS, Vorchheimer DA, Chronos N, Melloni C, Alexander JH, Harrington
RA, Tonkens RM, Becker RC, RusconiCP (2008) Phase 1b randomized study of antidotecontrolled modulation of factor IXa activity in patients with stable coronary artery disease.
Circulation 117(22):2865–2874
80. Chan MY, Rusconi CP, Alexander JH, Tonkens RM, Harrington RA, Becker RC (2008) A
randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor
IXa inhibitor. J Thromb Haemost 6(5):789–796
81. Cohen MG, Purdy DA, Rossi JS, Grinfeld LR, Myles SK, Aberle LH, Greenbaum AB, Fry E,
Chan MY, Tonkens RM, Zelenkofske S, Alexander JH, Harrington RA, Rusconi CP, Becker
RC (2010) First clinical application of an actively reversible direct factor IXa inhibitor
as an anticoagulation strategy in patients undergoing percutaneous coronary intervention.
Circulation 122(6):614–622
315
patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
(Writing Committee to Revise the 2002 Guidelines for the Management of Patients With
Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with
the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American
Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic
Emergency Medicine. J Am Coll Cardiol 50(7):e1–e157
69. Vavalle JP, Cohen MG (2012) The REG1 anticoagulation system: a novel actively controlled
factor IX inhibitor using RNA aptamer technology for treatment of acute coronary syndrome.
Future Cardiol 8(3):371–382
70. Rao SV, Jollis JG, Harrington RA, Granger CB, Newby LK, Armstrong PW, Moliterno
DJ, Lindblad L, Pieper K, Topol EJ, Stamler JS, Califf RM (2004) Relationship of
blood transfusion and clinical outcomes in patients with acute coronary syndromes. JAMA
292(13):1555–1562
71. Szlam F, Luan D, Bolliger D, Szlam AD, Levy JH, Varner JD, Tanaka KA (2010) Antifactor IXa Aptamer reduces propagation of thrombin generation in plasma anticoagulated
with warfarin. Thromb Res 125(5):432–437
72. Smith SB, Gailani D (2008) Update on the physiology and pathology of factor IX activation
by factor XIa. Expert Rev Hematol 1(1):87–98
73. Schmidt AE, Bajaj SP (2003) Structure-function relationships in factor IX and factor IXa.
Trends Cardiovasc Med 13(1):39–45
74. Rusconi CP, Roberts JD, Pitoc GA, Nimjee SM, White RR, Quick G, Scardino E, Fay WP,
Sullenger BA (2004) Antidote-mediated control of an anticoagulant aptamer in vivo. Nat
Biotechnol 22(11):1423–1428
75. Rusconi CP, Scardino E, Layzer J, Pitoc GA, Ortel TL, Monroe D, Sullenger BA (2002) RNA
aptamers as reversible antagonists of coagulation factor IXa. Nature 419(6902):90–94
76. Nimjee SM, Keys JR, Pitoc GA, Quick G, Rusconi CP, Sullenger BA (2006) A novel antidotecontrolled anticoagulant reduces thrombin generation and inflammation and improves cardiac
function in cardiopulmonary bypass surgery. Mol Ther 14(3):408–415
77. Dyke CK, Steinhubl SR, Kleiman NS, Cannon RO, Aberle LG, Lin M, Myles SK, Melloni C,
Harrington RA, Alexander JA, Becker RC, Rusconi CP (2006) First-in-human experience of
an antidote-controlled anticoagulant using RNA aptamer technology: a phase 1a pharmacodynamic evaluation of a drug-antidote pair for the controlled regulation of factor IXa activity.
Circulation 114(23):2490–2497
78. Povsic TJ, Vavalle JP, Aberle LH, Kasprzak JD, Cohen MG, Mehran R, Bode C, Buller
CE, Montalescot G, Cornel JH, Rynkiewicz A, Ring ME, Zeymer U, Natarajan M, Delarche
N, Zelenkofske SL, Becker RC, Alexander JH, Investigators RADAR (2013) A Phase 2,
randomized, partially blinded, active-controlled study assessing the efficacy and safety of
variable anticoagulation reversal using the REG1 system in patients with acute coronary
syndromes: results of the RADAR trial. Eur Heart J 34(31):2481–2489
79. Chan MY, Cohen MG, Dyke CK, Myles SK, Aberle LG, Lin M, Walder J, Steinhubl SR,
Gilchrist IC, Kleiman NS, Vorchheimer DA, Chronos N, Melloni C, Alexander JH, Harrington
RA, Tonkens RM, Becker RC, RusconiCP (2008) Phase 1b randomized study of antidotecontrolled modulation of factor IXa activity in patients with stable coronary artery disease.
Circulation 117(22):2865–2874
80. Chan MY, Rusconi CP, Alexander JH, Tonkens RM, Harrington RA, Becker RC (2008) A
randomized, repeat-dose, pharmacodynamic and safety study of an antidote-controlled factor
IXa inhibitor. J Thromb Haemost 6(5):789–796
81. Cohen MG, Purdy DA, Rossi JS, Grinfeld LR, Myles SK, Aberle LH, Greenbaum AB, Fry E,
Chan MY, Tonkens RM, Zelenkofske S, Alexander JH, Harrington RA, Rusconi CP, Becker
RC (2010) First clinical application of an actively reversible direct factor IXa inhibitor
as an anticoagulation strategy in patients undergoing percutaneous coronary intervention.
Circulation 122(6):614–622