Unstable angina NSTEMI Antiplatelet therapy recommendations

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The current most updated guidelines state that for UA/NSTEMI patients presenting to the hospital, aspirin should be administered immediately, and if the patient cannot take aspirin, another anti-platelet agent, namely clopidogrel or prasugrel (in PCI treated patients) should be given. UA/NSTEMI patients at moderate to high risk who will be undergoing PCI should be given dual antiplatelet therapy consisting of aspirin and one of the following; clopidogrel, ticagrelor, eptifibatide and prasugrel, depending on whether the second agent is given before or during PCI. Addtional situation specific guidelines are given below.

2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes (DO NOT EDIT) [1]

Initial Oral and Intravenous Antiplatelet Therapy in Patients With Definite or Likely NSTEACS Treated With an Initial Invasive or Ischemia-Guided Strategy

Class I
"1. Non–enteric-coated, chewable aspirin (162 mg to 325 mg) should be given to all patients with NSTE-ACS without contraindications as soon as possible after presentation, and a maintenance dose of aspirin (81 mg/d to 162 mg/d) should be continued indefinitely. (Level of Evidence: A)"
"2. In patients with NSTE-ACS who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance, a loading dose of clopidogrel followed by a daily maintenance dose should be administered. (Level of Evidence: B)"
"3. A P2Y12 inhibitor (either clopidogrel or ticagrelor) in addition to aspirin should be administered for up to 12 months to all patients with NSTE-ACS without contraindications who are treated with either an early invasive§ or ischemia-guided strategy. Options include:
Class IIa
"1. It is reasonable to use ticagrelor in preference to clopidogrel for P2Y12 treatment in patients with NSTE-ACS who undergo an early invasive or ischemia-guided strategy. (Level of Evidence: B)"


Class IIb
"1. In patients with NSTE-ACS treated with an early invasive strategy and dual antiplatelet therapy (DAPT) with intermediate/high-risk features (e.g., positive troponin), a GP IIb/IIIa inhibitor may be considered as part of initial antiplatelet therapy. Preferred options are eptifibatide or tirofiban. (Level of Evidence: B)"


2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Focused Update) (DO NOT EDIT)[2]

Antiplatelet therapy (DO NOT EDIT)[2]

Class I
"1. Aspirin should be administered to UA/NSTEMI patients as soon as possible after hospital presentation and continued indefinitely in patients who tolerate it.[3][4][5][6][7] (Level of Evidence: A)"
"2. A loading dose followed by daily maintenance dose of either clopidogrel[8][9][10] (Level of Evidence: C), prasugrel* (in PCI-treated patients)[11] (Level of Evidence: C), or ticagrelor**[12] (Level of Evidence: C) should be administered to UA/NSTEMI patients who are unable to take aspirin because of hypersensitivity or major GI intolerance."
"3. Patients with definite UA/NSTEMI at medium or high risk and in whom an initial invasive strategy is selected should receive dual antiplatelet therapy on presentation.[8][13][14][15] (Level of Evidence: A) Aspirin should be initiated on presentation.[3][16][17][5][6][7][18] (Level of Evidence: A) The choice of a second antiplatelet therapy to be added to aspirin on presentation includes 1 of the following:

a) Before PCI:

b) At the time of PCI:

"4. For UA/NSTEMI patients in whom an initial conservative (ie, noninvasive) strategy is selected, clopidogrel or Ticagrelor** (loading dose followed by daily maintenance dose) should be added to aspirin and anticoagulant therapy as soon as possible after admission and administered for up to 12 months.[19][25][8] (Level of Evidence: B)"
"5. For UA/NSTEMI patients in whom an initial conservative strategy is selected, if recurrent symptoms/ischemia, heart failure, or serious arrhythmias subsequently appear, then diagnostic angiography should be performed.[26][27] (Level of Evidence: A) Either an IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban[24][20][21] Level of Evidence: A), clopidogrel (loading dose followed by daily maintenance dose[8] Level of Evidence: B), or ticagrelor** (loading dose followed by daily maintenance dose[19] Level of Evidence: B) should be added to aspirin and anticoagulant therapy before diagnostic angiography (upstream). (Level of Evidence: C)"
"6. A loading dose of P2Y12 receptor inhibitor therapy is recommended for UA/NSTEMI patients for whom PCI is planned.*** Regimens should be 1 of the following:

a) Clopidogrel 600 mg should be given as early as possible before or at the time of PCI[28][29][30] (Level of Evidence: A) or

b) Prasugrel* 60 mg should be given promptly and no later than 1 hour after PCI once coronary anatomy is defined and a decision is made to proceed with PCI.[31] (Level of Evidence: B)

c) Ticagrelor** 180 mg should be given as early as possible before or at the time of PCI.[19] (Level of Evidence: B)"

"7. The duration and maintenance dose of P2Y12 receptor inhibitor therapy should be as follows:

a) In UA/NSTEMI patients undergoing PCI, either clopidogrel 75 mg daily[8][13], prasugrel* 10 mg daily[31], or ticagrelor** 90 mg twice daily[19] should be given for at least 12 months. (Level of Evidence: B)

b) If the risk of morbidity because of bleeding outweighs the anticipated benefits afforded by thienopyridine therapy, earlier discontinuation should be considered. (Level of Evidence: C)"

Class III: No Benefit
"1. Abciximab should not be administered to patients in whom PCI is not planned.[24][23] (Level of Evidence: A)"
"2. In UA/NSTEMI patients who are at low risk for ischemic events (eg, TIMI risk score <2 or =2) or at high risk of bleeding and who are already receiving aspirin and a P2Y12 receptor inhibitor, upstream GP IIb/IIIa inhibitors are not recommended.[32][33][34] (Level of Evidence: B)"
Class III: Harm
"1. In UA/NSTEMI patients with a prior history of stroke and/or TIA for whom PCI is planned, prasugrel* is potentially harmful as part of a dual antiplatelet therapy regimen.[31] (Level of Evidence: B)"
Class IIa
"1. For UA/NSTEMI patients in whom an initial conservative strategy is selected and who have recurrent ischemic discomfort with aspirin, a P2Y12 receptor inhibitor (clopidogrel or ticagrelor), and anticoagulant therapy, it is reasonable to add a GP IIb/IIIa inhibitor before diagnostic angiography. (Level of Evidence: C)"
"2. For UA/NSTEMI patients in whom an initial invasive strategy is selected, it is reasonable to omit administration of an IV GP IIb/IIIa inhibitor if bivalirudin is selected as the anticoagulant and at least 300 mg of clopidogrel was administered at least 6 hours earlier than planned catheterization or PCI.[35][36][37] (Level of Evidence: B)"
Class IIb
"1. For UA/NSTEMI patients in whom an initial conservative (ie, noninvasive) strategy is selected, it may be reasonable to add eptifibatide or tirofiban to anticoagulant and oral antiplatelet therapy.[20][21] (Level of Evidence: B)"
"2. Prasugrel* 60 mg may be considered for administration promptly upon presentation in patients with UA/NSTEMI for whom PCI is planned, before definition of coronary anatomy if both the risk for bleeding is low and the need for CABG is considered unlikely.[31][34] (Level of Evidence: C)"
"3. The use of upstream GP IIb/IIIa inhibitors may be considered in high-risk UA/NSTEMI patients already receiving aspirin and a P2Y12 receptor inhibitor (clopidogrel or ticagrelor) who are selected for an invasive strategy, such as those with elevated troponin levels, diabetes, or significant ST-segment depression, and who are not otherwise at high risk for bleeding.[20][21][26][32][38] (Level of Evidence: B)"
"4. In patients with definite UA/NSTEMI undergoing PCI as part of an early invasive strategy, the use of a loading dose of clopidogrel of 600 mg, followed by a higher maintenance dose of 150 mg daily for 6 days, then 75 mg daily may be reasonable in patients not considered at high risk for bleeding.[28] (Level of Evidence: B)"
“

* Patients weighing <60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10-mg once– daily maintenance dose. Consideration should be given to lowering the maintenance dose to 5 mg in patients who weigh <60 kg, although the effectiveness and safety of the 5-mg dose have not been studied prospectively. For post-PCI patients receiving a BMS or DES, a daily maintenance dose should be given for at least 12 months and for up to 15 months unless the risk of bleeding outweighs the anticipated net benefit afforded by a thienopyridine. Do not use prasugrel in patients with active pathological bleeding or a history of TIA or stroke. In patients >75 years of age, prasugrel is generally not recommended because of the increased risk of fatal and intracranial bleeding and uncertain benefit except in high-risk situations (patients with diabetes or a history of prior MI), in which its effect appears to be greater and its use may be considered. Do not start prasugrel in patients likely to undergo urgent CABG. When possible, discontinue prasugrel at least 7 days before any surgery.35 Additional risk factors for bleeding include body weight <60 kg, propensity to bleed, and concomitant use of medications that increase the risk of bleeding (eg, warfarin, heparin, fibrinolytic therapy, or chronic use of nonsteroidal anti-inflammatory drugs).

** The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily. Ticagrelor's benefits were observed irrespective of prior therapy with clopidogrel. When possible, discontinue ticagrelor at least 5 days before any surgery. Issues of patient compliance may be especially important. Consideration should be given to the potential and as yet undetermined risk of intracranial hemorrhage in patients with prior stroke or TIA.

*** Applies to patients who were not treated chronically with these medications.

”

References

  1. ↑ Ezra A. Amsterdam, MD, FACC; Nanette K. Wenger, MD et al.2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. JACC. September 2014 (ahead of print)
  2. ↑ 2.0 2.1 Jneid H, Anderson JL, Wright RS, Adams CD, Bridges CR, Casey DE; et al. (2012). "2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". J Am Coll Cardiol. 60 (7): 645–81. doi:10.1016/j.jacc.2012.06.004. PMID 22809746.
  3. ↑ 3.0 3.1 "Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration". BMJ. 308 (6921): 81–106. 1994. PMC 2539220. PMID 8298418.
  4. ↑ Antithrombotic Trialists' (ATT) Collaboration. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J; et al. (2009). "Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials". Lancet. 373 (9678): 1849–60. doi:10.1016/S0140-6736(09)60503-1. PMC 2715005. PMID 19482214. Review in: Ann Intern Med. 2009 Sep 15;151(6):JC3-4, JC3-5 Review in: Evid Based Med. 2009 Dec;14(6):172-3
  5. ↑ 5.0 5.1 Lewis HD, Davis JW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE; et al. (1983). "Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. Results of a Veterans Administration Cooperative Study". N Engl J Med. 309 (7): 396–403. doi:10.1056/NEJM198308183090703. PMID 6135989.
  6. ↑ 6.0 6.1 Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH (1997). "Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men". N Engl J Med. 336 (14): 973–9. doi:10.1056/NEJM199704033361401. PMID 9077376.
  7. ↑ 7.0 7.1 "Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. The RISC Group". Lancet. 336 (8719): 827–30. 1990. PMID 1976875.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 8.5 8.6 Yusuf S, Zhao F, Mehta SR, Chrolavicius S, Tognoni G, Fox KK; et al. (2001). "Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation". N Engl J Med. 345 (7): 494–502. doi:10.1056/NEJMoa010746. PMID 11519503. Review in: ACP J Club. 2002 Mar-Apr;136(2):45
  9. ↑ CAPRIE Steering Committee (1996). "A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee". Lancet. 348 (9038): 1329–39. PMID 8918275.
  10. ↑ Gollapudi RR, Teirstein PS, Stevenson DD, Simon RA (2004). "Aspirin sensitivity: implications for patients with coronary artery disease". JAMA. 292 (24): 3017–23. doi:10.1001/jama.292.24.3017. PMID 15613671.
  11. ↑ 11.0 11.1 Ge J, Zhu J, Hong BK, Boonbaichaiyapruck S, Goh YS, Hou CJ; et al. (2010). "Prasugrel versus clopidogrel in Asian patients with acute coronary syndromes: design and rationale of a multi-dose, pharmacodynamic, phase 3 clinical trial". Curr Med Res Opin. 26 (9): 2077–85. doi:10.1185/03007995.2010.502048. PMID 20629598.
  12. ↑ Husted S, James S, Becker RC, Horrow J, Katus H, Storey RF; et al. (2012). "Ticagrelor Versus Clopidogrel in Elderly Patients With Acute Coronary Syndromes: A Substudy From the Prospective Randomized PLATelet Inhibition and Patient Outcomes (PLATO) Trial". Circ Cardiovasc Qual Outcomes. 5 (5): 680–688. doi:10.1161/CIRCOUTCOMES.111.964395. PMID 22991347.
  13. ↑ 13.0 13.1 13.2 13.3 Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK; et al. (2001). "Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study". Lancet. 358 (9281): 527–33. PMID 11520521.
  14. ↑ 14.0 14.1 Boersma E, Harrington RA, Moliterno DJ, White H, Théroux P, Van de Werf F; et al. (2002). "Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials". Lancet. 359 (9302): 189–98. doi:10.1016/S0140-6736(02)07442-1. PMID 11812552. Review in: ACP J Club. 2002 Jul-Aug;137(1):2
  15. ↑ Steinhubl SR, Berger PB, Mann JT, Fry ET, DeLago A, Wilmer C; et al. (2002). "Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial". JAMA. 288 (19): 2411–20. PMID 12435254. Review in: ACP J Club. 2003 Jul-Aug;139(1):2
  16. ↑ Cairns JA, Gent M, Singer J, Finnie KJ, Froggatt GM, Holder DA; et al. (1985). "Aspirin, sulfinpyrazone, or both in unstable angina. Results of a Canadian multicenter trial". N Engl J Med. 313 (22): 1369–75. doi:10.1056/NEJM198511283132201. PMID 3903504.
  17. ↑ Cohen M, Adams PC, Parry G, Xiong J, Chamberlain D, Wieczorek I; et al. (1994). "Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Antithrombotic Therapy in Acute Coronary Syndromes Research Group". Circulation. 89 (1): 81–8. PMID 8281698.
  18. ↑ Théroux P, Ouimet H, McCans J, Latour JG, Joly P, Lévy G; et al. (1988). "Aspirin, heparin, or both to treat acute unstable angina". N Engl J Med. 319 (17): 1105–11. doi:10.1056/NEJM198810273191701. PMID 3050522.
  19. ↑ 19.0 19.1 19.2 19.3 19.4 19.5 Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C; et al. (2009). "Ticagrelor versus clopidogrel in patients with acute coronary syndromes". N Engl J Med. 361 (11): 1045–57. doi:10.1056/NEJMoa0904327. PMID 19717846. Review in: Ann Intern Med. 2009 Dec 15;151(12):JC6-4
  20. ↑ 20.0 20.1 20.2 20.3 20.4 20.5 "Inhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction. Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) Study Investigators". N Engl J Med. 338 (21): 1488–97. 1998. doi:10.1056/NEJM199805213382102. PMID 9599103.
  21. ↑ 21.0 21.1 21.2 21.3 21.4 21.5 "Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes. The PURSUIT Trial Investigators. Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy". N Engl J Med. 339 (7): 436–43. 1998. doi:10.1056/NEJM199808133390704. PMID 9705684.
  22. ↑ Simoons ML, GUSTO IV-ACS Investigators (2001). "Effect of glycoprotein IIb/IIIa receptor blocker abciximab on outcome in patients with acute coronary syndromes without early coronary revascularisation: the GUSTO IV-ACS randomised trial". Lancet. 357 (9272): 1915–24. PMID 11425411. Review in: ACP J Club. 2002 Mar-Apr;136(2):44
  23. ↑ 23.0 23.1 Ottervanger JP, Armstrong P, Barnathan ES, Boersma E, Cooper JS, Ohman EM; et al. (2003). "Long-term results after the glycoprotein IIb/IIIa inhibitor abciximab in unstable angina: one-year survival in the GUSTO IV-ACS (Global Use of Strategies To Open Occluded Coronary Arteries IV--Acute Coronary Syndrome) Trial". Circulation. 107 (3): 437–42. PMID 12551868.
  24. ↑ 24.0 24.1 24.2 "Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study". Lancet. 349 (9063): 1429–35. 1997. PMID 9164316.
  25. ↑ James SK, Roe MT, Cannon CP, Cornel JH, Horrow J, Husted S; et al. (2011). "Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management: substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial". BMJ. 342: d3527. doi:10.1136/bmj.d3527. PMC 3117310. PMID 21685437.
  26. ↑ 26.0 26.1 Cannon CP, Weintraub WS, Demopoulos LA, Vicari R, Frey MJ, Lakkis N; et al. (2001). "Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban". N Engl J Med. 344 (25): 1879–87. doi:10.1056/NEJM200106213442501. PMID 11419424. Review in: ACP J Club. 2002 Jan-Feb;136(1):4
  27. ↑ "Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators". Lancet. 354 (9180): 708–15. 1999. PMID 10475181.
  28. ↑ 28.0 28.1 Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB; et al. (2010). "Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-OASIS 7): a randomised factorial trial". Lancet. 376 (9748): 1233–43. doi:10.1016/S0140-6736(10)61088-4. PMID 20817281. Review in: Evid Based Med. 2011 Jun;16(3):80-1
  29. ↑ Cuisset T, Frere C, Quilici J, Morange PE, Nait-Saidi L, Carvajal J; et al. (2006). "Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing coronary stenting". J Am Coll Cardiol. 48 (7): 1339–45. doi:10.1016/j.jacc.2006.06.049. PMID 17010792.
  30. ↑ von Beckerath N, Taubert D, Pogatsa-Murray G, Schömig E, Kastrati A, Schömig A (2005). "Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial". Circulation. 112 (19): 2946–50. doi:10.1161/CIRCULATIONAHA.105.559088. PMID 16260639.
  31. ↑ 31.0 31.1 31.2 31.3 Sosnowski C (2008). "[Commentary to the article: Wiviott S D, Braunwald E, McCabe C H et al. Prasugrel versus clopidogrel in patients with acute coronary syndrome. N Engl J Med 2007; 357: 2001-15]". Kardiol Pol. 66 (2): 222–5, discussion 225-6. PMID 18634190.
  32. ↑ 32.0 32.1 Giugliano RP, White JA, Bode C, Armstrong PW, Montalescot G, Lewis BS; et al. (2009). "Early versus delayed, provisional eptifibatide in acute coronary syndromes". N Engl J Med. 360 (21): 2176–90. doi:10.1056/NEJMoa0901316. PMID 19332455.
  33. ↑ Sosnowski C (2007). "[Commentary to the article: Stone GW, Bertrand ME, Moses JW et al. Routine upstream initiation vs deferred selective use of glycoprotein IIB/III inhibitors in acute coronary syndromes: the ACUITY Timing trial JAMA 2007: 591-602]". Kardiol Pol. 65 (3): 327–31, discussion 332-3. PMID 17619281.
  34. ↑ 34.0 34.1 Subherwal S, Bach RG, Chen AY, Gage BF, Rao SV, Newby LK; et al. (2009). "Baseline risk of major bleeding in non-ST-segment-elevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA Guidelines) Bleeding Score". Circulation. 119 (14): 1873–82. doi:10.1161/CIRCULATIONAHA.108.828541. PMID 19332461.
  35. ↑ Stone GW, Bertrand ME, Moses JW, Ohman EM, Lincoff AM, Ware JH; et al. (2007). "Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing trial". JAMA. 297 (6): 591–602. doi:10.1001/jama.297.6.591. PMID 17299194.
  36. ↑ Stone GW, Ware JH, Bertrand ME, Lincoff AM, Moses JW, Ohman EM; et al. (2007). "Antithrombotic strategies in patients with acute coronary syndromes undergoing early invasive management: one-year results from the ACUITY trial". JAMA. 298 (21): 2497–506. doi:10.1001/jama.298.21.2497. PMID 18056903.
  37. ↑ Stone GW, White HD, Ohman EM, Bertrand ME, Lincoff AM, McLaurin BT; et al. (2007). "Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial". Lancet. 369 (9565): 907–19. doi:10.1016/S0140-6736(07)60450-4. PMID 17368152.
  38. ↑ Kastrati A, Mehilli J, Neumann FJ, Dotzer F, ten Berg J, Bollwein H; et al. (2006). "Abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention after clopidogrel pretreatment: the ISAR-REACT 2 randomized trial". JAMA. 295 (13): 1531–8. doi:10.1001/jama.295.13.joc60034. PMID 16533938. Review in: ACP J Club. 2006 Jul-Aug;145(1):8

References
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