361
Views
6
CrossRef citations to date
0
Altmetric
Review

Investigational drugs for the treatment of acute myocardial infarction: focus on antiplatelet and anticoagulant agents

, , , &
Pages 223-234 | Received 30 Jun 2018, Accepted 12 Dec 2018, Published online: 22 Dec 2018

References

  • Roth GA, Johnson C, Abajobir A, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol. 2017;70(1):1–25.
  • Moran D, Buckley A, Daly K, et al. Heart rate awareness in patients with chronic stable heart failure. A multi-center observational study. Int J Cardiol. 2014;177(2):380–384.
  • Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012;60(16):1581–1598.
  • Bentzon JF, Otsuka F, Virmani R, et al. Mechanisms of plaque formation and rupture. Circ Res. 2014;114(12):1852–1866.
  • Libby P, Tabas I, Fredman G, et al. Inflammation and its resolution as determinants of acute coronary syndromes. Circ Res. 2014;114(12):1867–1879.
  • Bhatt DL, Hulot J-S, Moliterno DJ, et al. Antiplatelet and anticoagulation therapy for acute coronary syndromes. Circ Res. 2014;114(12):1929–1943.
  • Davies MJ, Thomas AC. Plaque fissuring–the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. Heart. 1985;53(4):363–373.
  • Martin JF, Kristensen SD, Mathur A, et al. The causal role of megakaryocyte–platelet hyperactivity in acute coronary syndromes. Nat Rev Cardiol. 2012;9(11):658–670.
  • Kawai C. Pathogenesis of acute myocardial infarction. Novel regulatory systems of bioactive substances in the vessel wall. Circulation. 1994;90(2):1033–1043.
  • Sousa-Uva M, Neumann FJ, Ahlsson A, et al. ESC/EACTS guidelines on myocardial revascularization. Eur J Cardiothorac Surg. 2019;55:4-90.
  • Levine GN, Bates ER, Bittl JA, et al. ACC/AHA guideline focused update on duration of dual antiplatelet therapy in patients with coronary artery disease: a report of the American college of cardiology/American heart association task force on clinical practice guidelines: an update of the 2011 ACCF/AHA/SCAI guideline for percutaneous coronary intervention, 2011 ACCF/AHA guideline for coronary artery bypass graft surgery, 2012 ACC/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease, 2013 ACCF/AHA guideline for the management of ST-Elevation myocardial infarction, 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes, and 2014 ACC/AHA guideline on perioperative cardiovascular evaluation and management of patients undergoing noncardiac surgery. Circulation. 2016;134(10):e123–155. .
  • Franchi F, Rollini F, Angiolillo DJ. Antithrombotic therapy for patients with STEMI undergoing primary PCI. Nat Rev Cardiol. 2017;14(6):361–379.
  • Udell JA, Bonaca MP, Collet J-P, et al. Long-term dual antiplatelet therapy for secondary prevention of cardiovascular events in the subgroup of patients with previous myocardial infarction: a collaborative meta-analysis of randomized trials. Eur Heart J. 2016;37(4):390–399.
  • Price MJ. Cangrelor: pharmacology, clinical data, and role in percutaneous coronary intervention. Interv Cardiol Clin. 2017;6(1):39–47.
  • Gurbel PA, Tantry US. Drug insight: clopidogrel nonresponsiveness. Nat Clin Pract Cardiovasc Med. 2006;3(7):387–395.
  • Storey RF, Sanderson HM, White AE, et al. The central role of the P(2T) receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity. Br J Haematol. 2000;110(4):925–934.
  • Greenbaum AB, Grines CL, Bittl JA, et al. Initial experience with an intravenous P2Y12 platelet receptor antagonist in patients undergoing percutaneous coronary intervention: results from a 2-part, phase II, multicenter, randomized, placebo- and active-controlled trial. Am Heart J. 2006;151(3):689.e1-689.e10.
  • Harrington RA, Stone GW, McNulty S, et al. Platelet inhibition with cangrelor in patients undergoing PCI. N Engl J Med. 2009;361(24):2318–2329.
  • Bhatt DL, Lincoff AM, Gibson CM, et al. Intravenous Platelet Blockade with Cangrelor during PCI. N Engl J Med. 2009;361(24):2330–2341.
  • White HD, Chew DP, Dauerman HL, et al. Reduced immediate ischemic events with cangrelor in PCI: a pooled analysis of the CHAMPION trials using the universal definition of myocardial infarction. Am Heart J. 2012;163(2):182–190.e4.
  • Bhatt DL, Stone GW, Mahaffey KW, et al. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303–1313.
  • Gutierrez JA, Harrington RA, Blankenship JC, et al. The effect of cangrelor and access site on ischaemic and bleeding events: insights from CHAMPION PHOENIX. Eur Heart J. 2016;37(14):1122–1130.
  • Steg PG, Bhatt DL, Hamm CW, et al. Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data. Lancet Lond Engl. 2013;382(9909):1981–1992.
  • KENGREAL (cangrelor) for injection. [cited 2018 Jun 29] Available from: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/204958Orig1s000TOC.cfm
  • Westman PC, Lipinski MJ, Torguson R, et al. A comparison of cangrelor, prasugrel, ticagrelor, and clopidogrel in patients undergoing percutaneous coronary intervention: A network meta-analysis. Cardiovasc Revascularization Med Mol Interv. 2017;18(2):79–85.
  • Vaduganathan M, Qamar A, Singh A, et al. Cangrelor use since FDA approval: a single-center, real-world experience at a tertiary care hospital. J Am Coll Cardiol. 2017;69(4):463–464.
  • Ueno M, Rao SV, Angiolillo DJ. Elinogrel: pharmacological principles, preclinical and early phase clinical testing. Future Cardiol. 2010;6(4):445–453.
  • Berger JS, Roe MT, Gibson CM, et al. Safety and feasibility of adjunctive antiplatelet therapy with intravenous elinogrel, a direct-acting and reversible P2Y12 ADP-receptor antagonist, before primary percutaneous intervention in patients with ST-elevation myocardial infarction: the early rapid reversAl of platelet thromboSis with intravenous elinogrel before PCI to optimize reperfusion in acute myocardial infarction (ERASE MI) pilot trial. Am Heart J. 2009;158(6):998–1004.e1.
  • Welsh RC, Rao SV, Zeymer U, et al. A randomized, double-blind, active-controlled phase 2 trial to evaluate a novel selective and reversible intravenous and oral P2Y12 inhibitor elinogrel versus clopidogrel in patients undergoing nonurgent percutaneous coronary intervention: the INNOVATE-PCI trial. Circ Cardiovasc Interv. 2012;5(3):336–346.
  • Nieswandt B, Watson SP. Platelet-collagen interaction: is GPVI the central receptor? Blood. 2003;102(2):449–461.
  • Schulz C, Penz S, Hoffmann C, et al. Platelet GPVI binds to collagenous structures in the core region of human atheromatous plaque and is critical for atheroprogression in vivo. Basic Res Cardiol. 2008;103(4):356–367.
  • Ungerer M, Rosport K, Bültmann A, et al. Novel antiplatelet drug revacept (Dimeric Glycoprotein VI-Fc) specifically and efficiently inhibited collagen-induced platelet aggregation without affecting general hemostasis in humans. Circulation. 2011;123(17):1891–1899.
  • Phase A II randomised double-blind, placebo-controlled study of revacept in patients with stable coronary artery disease - full text view - clinicalTrials.gov. [cited 2018 May 12] Available from: https://clinicaltrials.gov/ct2/show/NCT03312855.
  • Ulrichts H, Silence K, Schoolmeester A, et al. Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs. Blood. 2011;118(3):757–765.
  • Bartunek J, Barbato E, Heyndrickx G, et al. Novel antiplatelet agents: ALX-0081, a nanobody directed towards von Willebrand factor. J Cardiovasc Transl Res. 2013;6(3):355–363.
  • Muller O, Bartunek J, Hamilos M, et al. von Willebrand factor inhibition improves endothelial function in patients with stable angina. J Cardiovasc Transl Res. 2013;6(3):364–370.
  • Comparative study of ALX-0081 versus GPIIb/IIIa Inhibitor in high risk percutaneous coronary intervention (PCI) Patients - Full Text View - ClinicalTrials.gov. [cited 2018 May 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT01020383.
  • Coughlin SR. Thrombin signalling and protease-activated receptors. Nature. 2000;407(6801):258–264.
  • Morrow DA, Braunwald E, Bonaca MP, et al. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med. 2012;366(15):1404–1413.
  • Goto S, Ogawa H, Takeuchi M, et al. Double-blind, placebo-controlled phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease. Eur Heart J. 2010;31(21):2601–2613.
  • O’Donoghue ML, Bhatt DL, Wiviott SD, et al. Safety and tolerability of atopaxar in the treatment of patients with acute coronary syndromes: the lessons from antagonizing the cellular effects of thrombin–acute coronary syndromes trial. Circulation. 2011;123(17):1843–1853.
  • Wiviott SD, Flather MD, O’Donoghue ML, et al. Randomized trial of atopaxar in the treatment of patients with coronary artery disease: the lessons from antagonizing the cellular effect of thrombin–coronary artery disease trial. Circulation. 2011;123(17):1854–1863.
  • Tricoci P, Huang Z, Held C, et al. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med. 2012;366(1):20–33.
  • Tricoci P, Lokhnygina Y, Huang Z, et al. Vorapaxar with or without clopidogrel after non-ST-segment elevation acute coronary syndromes: results from the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome trial. Am Heart J. 2014;168(6):869–877.e1.
  • Cornel JH, Tricoci P, Lokhnygina Y, et al. Glycoprotein IIb/IIIa receptor inhibitors in combination with vorapaxar, a platelet thrombin receptor antagonist, among patients with non-ST-segment elevation acute coronary syndromes (from the TRACER Trial). Am J Cardiol. 2015;115(10):1325–1332.
  • Valgimigli M, Tricoci P, Huang Z, et al. Usefulness and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention (from the TRACER Trial). Am J Cardiol. 2014;114(5):665–673.
  • Whellan DJ, Tricoci P, Chen E, et al. Vorapaxar in acute coronary syndrome patients undergoing coronary artery bypass graft surgery: subgroup analysis from the TRACER trial (thrombin receptor antagonist for clinical event reduction in acute coronary syndrome). J Am Coll Cardiol. 2014;63(11):1048–1057.
  • Leonardi S, Tricoci P, White HD, et al. Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA·CER) trial. Eur Heart J. 2013;34(23):1723–1731.
  • White HD, Huang Z, Tricoci P, et al. Reduction in overall occurrences of ischemic events with vorapaxar: results from TRACER. J Am Heart Assoc. 2014;3:4.
  • van Diepen S, Tricoci P, Podder M, et al. Efficacy and safety of vorapaxar in non-ST-segment elevation acute coronary syndrome patients undergoing noncardiac surgery. J Am Heart Assoc. 2015;4:12.
  • Scirica BM, Bonaca MP, Braunwald E, et al. Vorapaxar for secondary prevention of thrombotic events for patients with previous myocardial infarction: a prespecified subgroup analysis of the TRA 2°P-TIMI 50 trial. Lancet Lond Engl. 2012;380(9850):1317–1324.
  • Cavender MA, Scirica BM, Bonaca MP, et al. Vorapaxar in patients with diabetes mellitus and previous myocardial infarction: findings from the thrombin receptor antagonist in secondary prevention of atherothrombotic ischemic events-TIMI 50 trial. Circulation. 2015;131(12):1047–1053.
  • Bonaca MP, Scirica BM, Braunwald E, et al. Coronary stent thrombosis with vorapaxar versus placebo: results from the TRA 2° P-TIMI 50 trial. J Am Coll Cardiol. 2014;64(22):2309–2317.
  • Bohula EA, Aylward PE, Bonaca MP, et al. Efficacy and safety of vorapaxar with and without a thienopyridine for secondary prevention in patients with previous myocardial infarction and no history of stroke or transient ischemic attack: results from TRA 2°P-TIMI 50. Circulation. 2015;132(20):1871–1879.
  • Berg DD, Bonaca MP, Braunwald E, et al. Outcomes in stable patients with previous atherothrombotic events receiving vorapaxar who experience a new acute coronary event (from TRA2°P-TIMI 50). Am J Cardiol. 2016;117(7):1055–1058.
  • Lam S, Tran T. Vorapaxar: A protease-activated receptor antagonist for the prevention of thrombotic events. Cardiol Rev. 2015;23(5):261–267.
  • Research C for DE and. drug approvals and databases - drug trials snapshot: zontivity (vorapaxar). [cited 2018 May 12]. Available from: https://www.fda.gov/Drugs/InformationOnDrugs/ucm423935.htm.
  • Magnani G, Bonaca MP, Braunwald E, et al. Efficacy and safety of vorapaxar as approved for clinical use in the United States. J Am Heart Assoc. 2015;4(3):e001505.
  • Vorapaxar: the drug and its applications. american college of cardiology. [cited 2018 May 12]. Available from: http://www.acc.org%2flatest-in-cardiology%2farticles%2f2016%2f05%2f18%2f13%2f58%2fvorapaxar
  • Vorapaxar in patients with prior myocardial infarction treated with prasugrel and ticagrelor - full text view - clinicalTrials.gov. [cited 2018 May 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT02545933
  • Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013;368(21):2004–2013.
  • Julian DG, Chamberlain DA, Pocock SJ. A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial. BMJ. 1996;313(7070):1429–1431.
  • CARS investigators. Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Lancet. 1997;350(9075):389–396.
  • Fiore LD, Ezekowitz MD, Brophy MT, et al. Department of veterans affairs cooperative studies program clinical trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. Circulation. 2002;105(5):557–563.
  • De Caterina R, Husted S, Wallentin L, et al. New oral anticoagulants in atrial fibrillation and acute coronary syndromes: ESC working group on thrombosis-task force on anticoagulants in heart disease position paper. J Am Coll Cardiol. 2012;59(16):1413–1425.
  • Eriksson UG, Bredberg U, Hoffmann K-J, et al. Absorption, distribution, metabolism, and excretion of ximelagatran, an oral direct thrombin inhibitor, in rats, dogs, and humans. Drug Metab Dispos. 2003;31(3):294–305.
  • Wallentin L, Wilcox RG, Weaver WD, et al. Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomised controlled trial. Lancet Lond Engl. 2003;362(9386):789–797.
  • Exanta withdrawn from market worldwide. Medscape. [cited 2018 May 12]. Available from: http://www.medscape.com/viewarticle/788220
  • Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139–1151.
  • Hohnloser SH, Oldgren J, Yang S, et al. Myocardial ischemic events in patients with atrial fibrillation treated with dabigatran or warfarin in the RE-LY (Randomized evaluation of long-term anticoagulation therapy) trial. Circulation. 2012;125(5):669–676.
  • Douxfils J, Buckinx F, Mullier F, et al. Dabigatran etexilate and risk of myocardial infarction, other cardiovascular events, major bleeding, and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2014;3(3):e000515.
  • Uchino K, Hernandez AV. Dabigatran association with higher risk of acute coronary events: meta-analysis of noninferiority randomized controlled trials. Arch Intern Med. 2012;172(5):397–402.
  • Oldgren J, Budaj A, Granger CB, et al. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J. 2011;32(22):2781–2789.
  • Devereaux PJ, Duceppe E, Guyatt G, et al. Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial. Lancet Lond Engl. 2018;391(10137):2325–2334.
  • Lauffenburger JC, Farley JF, Gehi AK, et al. Effectiveness and safety of dabigatran and warfarin in real-world US patients with non-valvular atrial fibrillation: a retrospective cohort study. J Am Heart Assoc. 2015;4:4.
  • Larsen TB, Rasmussen LH, Skjøth F, et al. Efficacy and safety of dabigatran etexilate and warfarin in “real-world” patients with atrial fibrillation: a prospective nationwide cohort study. J Am Coll Cardiol. 2013;61(22):2264–2273.
  • Lee CJ-Y, Gerds TA, Carlson N, et al. Risk of myocardial infarction in anticoagulated patients with atrial fibrillation. J Am Coll Cardiol. 2018;72(1):17–26.
  • Wei A-H, Gu Z-C, Zhang C, et al. Increased risk of myocardial infarction with dabigatran etexilate: fact or fiction? A critical meta-analysis of over 580,000 patients from integrating randomized controlled trials and real-world studies. Int J Cardiol. 2018;267:1–7.
  • Hohnloser SH, Eikelboom JW. Direct oral anticoagulants and myocardial infarction: the dust is settling. J Am Coll Cardiol. 2018;72(1):27–28.
  • Optimal antithrombotic therapy for ACS patients concomitant AF undergoing new generation des implantation - full text view - clinicaltrials.gov. [cited 2018 May 12]. Available from: https://clinicaltrials.gov/ct2/show/NCT03234114
  • Turpie AGG. Oral, direct factor xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Arterioscler Thromb Vasc Biol. 2007;27(6):1238–1247.
  • APPRAISE Steering Committee and Investigators, Alexander Jh, Becker Rc, et al. Apixaban, an oral, direct, selective factor Xa inhibitor, in combination with antiplatelet therapy after acute coronary syndrome: results of the apixaban for prevention of acute ischemic and safety events (APPRAISE) trial. Circulation. 2009;119(22):2877–2885.
  • Alexander JH, Lopes RD, James S, et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med. 2011;365(8):699–708.
  • Lopes RD, Vora AN, Liaw D, et al. An open-Label, 2 × 2 factorial, randomized controlled trial to evaluate the safety of apixaban vs. vitamin K antagonist and aspirin vs. placebo in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention: rationale and design of the AUGUSTUS trial. Am Heart J. 2018;200:17–23.
  • Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981–992.
  • Tornyos A, Vorobcsuk A, Kupó P, et al. Apixaban and risk of myocardial infarction: meta-analysis of randomized controlled trials. J Thromb Thrombolysis. 2015;40(1):1–11.
  • Kubitza D, Becka M, Wensing G, et al. Safety, pharmacodynamics, and pharmacokinetics of BAY 59-7939–an oral, direct factor Xa inhibitor–after multiple dosing in healthy male subjects. Eur J Clin Pharmacol. 2005;61(12):873–880.
  • Mega JL, Braunwald E, Mohanavelu S, et al. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet Lond Engl. 2009;374(9683):29–38.
  • Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366(1):9–19. .
  • Gibson CM, Chakrabarti AK, Mega J, et al. Reduction of stent thrombosis in patients with acute coronary syndromes treated with rivaroxaban in ATLAS-ACS 2 TIMI 51. J Am Coll Cardiol. 2013;62(4):286–290.
  • Cavender MA, Gibson CM, Braunwald E, et al. The effect of rivaroxaban on myocardial infarction in the ATLAS ACS 2 - TIMI 51 trial. Eur Heart J Acute Cardiovasc Care. 2015;4(5):468–474.
  • Korjian S, Braunwald E, Daaboul Y. et al. Safety and efficacy of rivaroxaban for the secondary prevention following acute coronary syndromes among biomarker-positive patients: insights from the ATLAS ACS 2-TIMI 51 trial. Eur Heart J Acute Cardiovasc Care. 2017 December. 2048872617745003. Doi: 10.1177/2048872617745003
  • Roe MT, Ohman EM. A new era in secondary prevention after acute coronary syndrome. N Engl J Med. 2012;366(1):85–87.
  • FDA again denies rivaroxaban ACS indication. Medscape. [cited 2018 May 12]. Available from: http://www.medscape.com/viewarticle/820651
  • Xarelto® - secondary prevention in acute coronary syndrome. [cited 2018 May 12]. Available from: https://www.xarelto.com/en/indications/secondary-prevention-in-acute-coronary-syndrome/
  • Roffi M, Patrono C, Collet JP, et al. 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation: task force for the management of acute coronary syndromes in patients presenting without persistent st-segment elevation of the European Society of Cardiology (ESC). Eur Heart J. 2016 Jan 14;37(3):267–315.
  • de Meent DG, Heeringa M, Kadokura T, et al. YM150, an oral direct inhibitor of factor Xa, Demonstrated a predictable and dose-proportional pharmacokinetic/pharmacodynamic profile after single and multiple dosing: results from three studies. Blood. 2010;116(21):3323.
  • Steg PG, Mehta SR, Jukema JW, et al. RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following acute coronary syndrome. Eur Heart J. 2011;32(20):2541–2554.
  • Goldstein S, Bates ER, Bhatt DL, et al. Phase 2 study of TAK-442, an oral factor Xa inhibitor, in patients following acute coronary syndrome. Thromb Haemost. 2014;111(6):1141–1152.
  • Chu V, Brown K, Colussi D, et al. Pharmacological characterization of a novel factor Xa inhibitor, FXV673. Thromb Res. 2001;103(4):309–324.
  • Sabatine MS, Antman EM, Widimsky P, et al. Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial. Lancet Lond Engl. 2009;374(9692):787–795.
  • Steg PG, Mehta SR, Pollack CV, et al. Anticoagulation with otamixaban and ischemic events in non–ST-segment elevation acute coronary syndromes: the TAO randomized clinical trial. JAMA. 2013;310(11):1145–1155.
  • Sanofi’s Investigational iniparib, otamixaban fail to meet goals, ends programs. RTTNews. [cited 2018 May 12]. Available from: http://www.rttnews.com/2129222/sanofi-s-investigational-iniparib-otamixaban-fail-to-meet-goals-ends-programs.aspx

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.