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Antiplatelet therapy to support PCI

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2] Anahita Deylamsalehi, M.D.[3]

Overview

Overview

Dual anti-platelet therapy (aspirin and oral P2Y12 inhibitors) is the main therapy for the prevention of thrombotic complications in patients with PCI. It has been recommended to avoid routine P2Y12 inhibitor treatment in patients with stable angina whose coronary anatomy is unknown. Antiplatelet medications are divided into those which can be used orally or intravenously. Clopidogrel, ticagrelor and prasugrel are the common present-day oral P2Y12 inhibitors with different dosage, characteristics and considerations. On the other hand, aspirin has been used as a key agent in prevention of coronary thrombosis with balloon angioplasty and in patients with chronic vascular disease. Usage of aspirin is recommended in the periprocedural period due to its effect on reducing ischemic complications after PCI. Intravenous antiplatelets such as abciximab, eptifibatide, tirofiban, and cangrelor have been studied in different clinical trials. Among these medications only cangrelor is a P2Y12 inhibitor and the other ones are glycoprotein IIb/IIIa inhibitor. Antiplatelet therapy in STEMI patients who had been treated with fibrinolytics who are undergoing PCI is high risk due to higher rate of bleeding and ischemia. However, clopidogrel was studied in conjunction with fibrinolytic therapy and led to 46% lower rate of cardiovascular death, recurrent MI and stroke within the 30 days after PCI with an unchanged rate of minor and major bleeding.

Antiplatelet Therapy to Support PCI

Antiplatelet Therapy to Support PCI

Oral Antiplatelets


Medication Loading Dose Maintanance Dose
Aspirin 162-325 mg (can be chewed to achieve faster action) 75-100 mg daily
Clopidogrel 600 mg (a lower loading dose of 300 mg is recommended in older patients or in patients after fibrinolytic therapy) 75 mg daily
Prasugrel 60 mg 10 mg daily
Ticagrelor 180 mg (can be chewed to achieve faster action) 90 mg twice a day

Intravenous Antiplatelets


Medication Loading Dose Maintanance Dose
Abciximab (glycoprotein IIb/IIIa inhibitor) Bolus of 0.25 mg/kg 0.125 mg/kg/min infusion (maximum 10 g/min) for 12 hours
Eptifibatide (glycoprotein IIb/IIIa inhibitor) Double bolus of 180 mg/kg (given at a 10-min interval) 2.0 mg/kg/min for up to 18 hours
Tirofiban (glycoprotein IIb/IIIa inhibitor) Bolus of 25 mg/kg over 3 minutes Infusion of 0.15 mg/kg/min for up to 18 hours
Cangrelor Bolus of 30 mg/kg Infusion 4 mg/kg/min for at least 2 hours or duration of the procedure, whichever is longer

Glycoprotein IIb/IIIa Receptor Inhibitors

Antiplatelet Therapy In Patients Who Were Treated With Fibrinolytic Therapy

2021 ACA Revascularization Guideline

2021 ACA Revascularization Guideline

Class 1 Recommendation, Level of Evidence: ‌B-R[1][18][19][20][13][22][3][38][39][40][41][42][16][43]
1. A loading dose of aspirin, followed by daily dosing is recommended to reduce ischemic events in patients who are undergoing PCI.

2. A loading dose of P2Y12 inhibitor, followed by daily dosing is recommended to reduce ischemic events in patients with ACS who are undergoing PCI.

Class 1 Recommendation, Level of Evidence: C-LD [1][13][38][41][43][44][8][12]
1. A loading dose of clopidogrel, followed by daily dosing is recommended to reduce ischemic events in patients with stable ischemic heart disease (SIHD) who are undergoing PCI.

2. A loading dose of 300 mg of clopidogrel, followed by daily dosing is recommended to reduce ischemic events in patients undergoing PCI within 24 hours after fibrinolytic therapy.

Class IIa, Level of Evidence: ‌C-LD[1][45][30]
Intravenous glycoprotein IIb/IIIa inhibitors are a reasonable choice in order to improve procedural success in patients with ACS who are undergoing PCI and have a large thrombus burden, no-reflow, or slow flow.
Class 2b Recommendation, Level of Evidence: B-R [1][22][16][15][27][26][29]
1. Using ticagrelor or prasugrel is preferred to clopidogrel in order to decrease ischemic events (including stent thrombosis) in ACS patients undergoing PCI.

2. Intravenous cangrelor is recommended in order to reduce periprocedural ischemic events among P2Y12 inhibitor naïve patients who are undergoing PCI.

Class 2b Recommendation, Level of Evidence: B-R[1]
Ticagrelor could be a reasonable alternative over clopidogrel in order to decrease ischemic events in patients older than 75 years old who are undergoing PCI within 24 hours after fibrinolytic therapy.
Class 3 Recommendation: HARM, Level of Evidence: B-R[1][33][34][35]
1. Prasugrel should not be administered in patients with a history of stroke or transient ischemic attack who are undergoing PCI.

2. The routine use of an intravenous glycoprotein IIb/IIIa inhibitor is not recommended in patients with stable ischemic heart disease undergoing PCI.

2011 ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention (DO NOT EDIT)[46]

2011 ACCF/AHA/SCAI Guidelines for Percutaneous Coronary Intervention (DO NOT EDIT)[46]

2011 AHA guidelines recommend the use of antiplatelet therapy aspirin (Level of Evidence: B) and P2Y12 receptor inhibitor (clopidogrel, prasugrel and ticagrelor) (Level of Evidence: A) to support PCI in patients with ACS. Few randomised trials have been conducted showing comparison of clopidogrel with aspirin and other P2Y12 inhibitors (prasugrel and ticagrelor) in terms of clinical benefit and risk of bleeding when given in patients undergoing PCI.[47][13][48][22][16] However, there is limited data comparing new P2Y12 receptor inhibitors (prasugrel and ticagrelor) for downstream and upstream therapy in patients undergoing PCI with non ST elevation MI in terms of clinical benefit and adverse effects. Hence, a new large scale randomised open label trial called DUBIUS is in process in Italy comparing two new P2Y12 inhibitors prasugrel and ticagrelor for pretreatment in patients with non ST elevation MI undergoing PCI. It is a trial designed for superiority comparing downstream therapy over upstream therapy in terms of NACE (net adverse cardaic effect) and risk of major bleeding (BARC 3, 4 and 5). Another endpoint considered in the trial is non inferiority comparison between prasugrel and ticagrelor in terms of potency of the drug for clinical benefit and NACE.

Oral Antiplatelet Therapy (DO NOT EDIT)[46]

Class I
“1. Patients already taking daily aspirin therapy should take 81 mg to 325 mg before PCI.[49][10][50] (Level of Evidence: B)”
“2. Patients not on aspirin therapy should be given non-enteric aspirin 325 mg before PCI.[49][50] (Level of Evidence: B)”
“3. After PCI, use of aspirin should be continued indefinitely.[40][18][20][51] (Level of Evidence: A)”
“4. A loading dose of a P2Y12 receptor inhibitor should be given to patients undergoing PCI with stenting.[47][13][48][22][16] (Level of Evidence: A) Options include:
a. Clopidogrel 600 mg (ACS and non-ACS patients).[47][47][13][48][22][16][13][48](Level of Evidence: B)
b. Prasugrel 60 mg (ACS patients).[47][13][48][22][16][22] (Level of Evidence: B)
c. Ticagrelor 180 mg (ACS patients).[16] (Level of Evidence: B)“
“5. The loading dose of clopidogrel for patients undergoing PCI after fibrinolytic therapy should be 300 mg within 24 hours and 600 mg more than 24 hours after receiving fibrinolytic therapy.[13][52] (Level of Evidence: C)”
“6. Patients should be counseled on the need for and risks of dual antiplatelet therapy (DAPT) before placement of intra-coronary stents, especially drug eluting stents (DES), and alternative therapies should be pursued if patients are unwilling or unable to comply with the recommended duration of dual antiplatelet therapy.[53] (Level of Evidence: C)”
“7. The duration of P2Y12 receptor inhibitor therapy after stent implantation should generally be as follows:
a. In patients receiving a stent (bare metal stent (BMS) or drug eluting stent (DES)) during PCI for ACS, P2Y12 receptor inhibitor therapy should be given for at least 12 months. Options include clopidogrel 75 mg daily [14],prasugrel 10 mg daily [22], and ticagrelor 90 mg twice daily.[16] (Level of Evidence: B)
b. In patients receiving drug eluting stent (DES) for a non-ACS indication, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at high risk of bleeding.[53][54][55] (Level of Evidence: B)
c. In patients receiving bare metal stent (BMS) for a non-ACS indication, clopidogrel should be given for a minimum of 1 month and ideally up to 12 months (unless the patient is at increased risk of bleeding; then it should be given for a minimum of 2 weeks).[53][8] (Level of Evidence: B)“
Class III (Harm)
“1. Prasugrel should not be administered to patients with a prior history of stroke or transient ischemic attack.[22] (Level of Evidence: B)”
Class IIa
“1. After PCI, it is reasonable to use aspirin 81 mg per day in preference to higher maintenance doses.[10][56][57][11][58] (Level of Evidence: B)”
“2. If the risk of morbidity from bleeding outweighs the anticipated benefit afforded by a recommended duration of P2Y12 receptor inhibitor therapy after stent implantation, earlier discontinuation (e.g.,less than 12 months) of P2Y12 receptor inhibitor therapy is reasonable. (Level of Evidence: C)”
Class IIb
“1. Continuation of dual antiplatelet therapy (DAPT) beyond 12 months may be considered in patients undergoing drug eluting stent (DES) implantation.[22][16] (Level of Evidence: C)”

Dual Antiplatelet Therapy Compliance and Stent Thrombosis (DO NOT EDIT) [46]

Class III (Harm)

“1. PCI with coronary stenting (BMS or DES) should not be performed if the patient is not likely to be able to tolerate and comply with dual antiplatelet therapy (DAPT) for the appropriate duration of treatment based on the type of stent implanted. [53][9][59][60](Level of Evidence: B)”

References

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 Writing Committee Members. Lawton JS, Tamis-Holland JE, Bangalore S, Bates ER, Beckie TM; et al. (2022). “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines”. J Am Coll Cardiol. 79 (2): e21–e129. doi:10.1016/j.jacc.2021.09.006. PMID 34895950 Check |pmid= value (help).
  2. ↑ Widimsky P, Motovská Z, Simek S, Kala P, Pudil R, Holm F; et al. (2008). “Clopidogrel pre-treatment in stable angina: for all patients > 6 h before elective coronary angiography or only for angiographically selected patients a few minutes before PCI? A randomized multicentre trial PRAGUE-8”. Eur Heart J. 29 (12): 1495–503. doi:10.1093/eurheartj/ehn169. PMC 2429977. PMID 18441320.
  3. ↑ 3.0 3.1 Montalescot G, van ‘t Hof AW, Lapostolle F, Silvain J, Lassen JF, Bolognese L; et al. (2014). “Prehospital ticagrelor in ST-segment elevation myocardial infarction”. N Engl J Med. 371 (11): 1016–27. doi:10.1056/NEJMoa1407024. PMID 25175921.
  4. ↑ Dörler J, Edlinger M, Alber HF, Altenberger J, Benzer W, Grimm G; et al. (2011). “Clopidogrel pre-treatment is associated with reduced in-hospital mortality in primary percutaneous coronary intervention for acute ST-elevation myocardial infarction”. Eur Heart J. 32 (23): 2954–61. doi:10.1093/eurheartj/ehr360. PMID 21920970.
  5. ↑ Zeymer U, Arntz HR, Mark B, Fichtlscherer S, Werner G, Schöller R; et al. (2012). “Efficacy and safety of a high loading dose of clopidogrel administered prehospitally to improve primary percutaneous coronary intervention in acute myocardial infarction: the randomized CIPAMI trial”. Clin Res Cardiol. 101 (4): 305–12. doi:10.1007/s00392-011-0393-1. PMID 22186968.
  6. ↑ Montalescot G, Bolognese L, Dudek D, Goldstein P, Hamm C, Tanguay JF; et al. (2013). “Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes”. N Engl J Med. 369 (11): 999–1010. doi:10.1056/NEJMoa1308075. PMID 23991622.
  7. ↑ Tarantini G, Mojoli M, Varbella F, Caporale R, Rigattieri S, Andò G; et al. (2020). “Timing of Oral P2Y12 Inhibitor Administration in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome”. J Am Coll Cardiol. 76 (21): 2450–2459. doi:10.1016/j.jacc.2020.08.053. PMID 32882390 Check |pmid= value (help).
  8. ↑ 8.0 8.1 8.2 8.3 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. doi:10.1001/jama.288.19.2411. PMID 12435254. Review in: ACP J Club. 2003 Jul-Aug;139(1):2
  9. ↑ 9.0 9.1 Leon MB, Baim DS, Popma JJ, Gordon PC, Cutlip DE, Ho KK; et al. (1998). “A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators”. N Engl J Med. 339 (23): 1665–71. doi:10.1056/NEJM199812033392303. PMID 9834303.
  10. ↑ 10.0 10.1 10.2 Jolly SS, Pogue J, Haladyn K, Peters RJ, Fox KA, Avezum A; et al. (2009). “Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study”. Eur Heart J. 30 (8): 900–7. doi:10.1093/eurheartj/ehn417. PMID 18819961.
  11. ↑ 11.0 11.1 Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Baggish JS, Bhatt DL; et al. (2005). “Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials”. Am J Cardiol. 95 (10): 1218–22. doi:10.1016/j.amjcard.2005.01.049. PMID 15877994.
  12. ↑ 12.0 12.1 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.
  13. ↑ 13.00 13.01 13.02 13.03 13.04 13.05 13.06 13.07 13.08 13.09 Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P; et al. (2005). “Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study”. JAMA. 294 (10): 1224–32. doi:10.1001/jama.294.10.1224. PMID 16143698. Review in: ACP J Club. 2006 Mar-Apr;144(2):29
  14. ↑ 14.0 14.1 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. doi:10.1016/s0140-6736(01)05701-4. PMID 11520521.
  15. ↑ 15.0 15.1 Montalescot G, Wiviott SD, Braunwald E, Murphy SA, Gibson CM, McCabe CH; et al. (2009). “Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial”. Lancet. 373 (9665): 723–31. doi:10.1016/S0140-6736(09)60441-4. PMID 19249633. Review in: Ann Intern Med. 2009 Jun 16;150(12):JC6-10
  16. ↑ 16.00 16.01 16.02 16.03 16.04 16.05 16.06 16.07 16.08 16.09 16.10 16.11 16.12 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
  17. ↑ Menichelli M, Neumann FJ, Ndrepepa G, Mayer K, Wöhrle J, Bernlochner I; et al. (2020). “Age- and Weight-Adapted Dose of Prasugrel Versus Standard Dose of Ticagrelor in Patients With Acute Coronary Syndromes : Results From a Randomized Trial”. Ann Intern Med. 173 (6): 436–444. doi:10.7326/M20-1806. PMID 32687741 Check |pmid= value (help).
  18. ↑ 18.0 18.1 18.2 Antithrombotic Trialists’ Collaboration (2002). “Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients”. BMJ. 324 (7329): 71–86. doi:10.1136/bmj.324.7329.71. PMC 64503. PMID 11786451. Review in: ACP J Club. 2002 Jul-Aug;137(1):5
  19. ↑ 19.0 19.1 “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.
  20. ↑ 20.0 20.1 20.2 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
  21. ↑ Schwartz L, Bourassa MG, Lespérance J, Aldridge HE, Kazim F, Salvatori VA; et al. (1988). “Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty”. N Engl J Med. 318 (26): 1714–9. doi:10.1056/NEJM198806303182603. PMID 2967433.
  22. ↑ 22.00 22.01 22.02 22.03 22.04 22.05 22.06 22.07 22.08 22.09 22.10 22.11 22.12 Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S; et al. (2007). “Prasugrel versus clopidogrel in patients with acute coronary syndromes”. N Engl J Med. 357 (20): 2001–15. doi:10.1056/NEJMoa0706482. PMID 17982182.
  23. ↑ Stone GW, Grines CL, Cox DA, Garcia E, Tcheng JE, Griffin JJ; et al. (2002). “Comparison of angioplasty with stenting, with or without abciximab, in acute myocardial infarction”. N Engl J Med. 346 (13): 957–66. doi:10.1056/NEJMoa013404. PMID 11919304.
  24. ↑ 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.
  25. ↑ Valgimigli M, Campo G, Percoco G, Bolognese L, Vassanelli C, Colangelo S; et al. (2008). “Comparison of angioplasty with infusion of tirofiban or abciximab and with implantation of sirolimus-eluting or uncoated stents for acute myocardial infarction: the MULTISTRATEGY randomized trial”. JAMA. 299 (15): 1788–99. doi:10.1001/jama.299.15.joc80026. PMID 18375998.
  26. ↑ 26.0 26.1 26.2 Bhatt DL, Stone GW, Mahaffey KW, Gibson CM, Steg PG, Hamm CW; et al. (2013). “Effect of platelet inhibition with cangrelor during PCI on ischemic events”. N Engl J Med. 368 (14): 1303–13. doi:10.1056/NEJMoa1300815. PMID 23473369. Review in: Ann Intern Med. 2013 Jun 18;158(12):JC5
  27. ↑ 27.0 27.1 27.2 Bhatt DL, Lincoff AM, Gibson CM, Stone GW, McNulty S, Montalescot G; et al. (2009). “Intravenous platelet blockade with cangrelor during PCI”. N Engl J Med. 361 (24): 2330–41. doi:10.1056/NEJMoa0908629. PMID 19915222.
  28. ↑ Harrington RA, Stone GW, McNulty S, White HD, Lincoff AM, Gibson CM; et al. (2009). “Platelet inhibition with cangrelor in patients undergoing PCI”. N Engl J Med. 361 (24): 2318–29. doi:10.1056/NEJMoa0908628. PMID 19915221.
  29. ↑ 29.0 29.1 29.2 29.3 Steg PG, Bhatt DL, Hamm CW, Stone GW, Gibson CM, Mahaffey KW; et al. (2013). “Effect of cangrelor on periprocedural outcomes in percutaneous coronary interventions: a pooled analysis of patient-level data”. Lancet. 382 (9909): 1981–92. doi:10.1016/S0140-6736(13)61615-3. PMID 24011551.
  30. ↑ 30.0 30.1 30.2 Montalescot G, Barragan P, Wittenberg O, Ecollan P, Elhadad S, Villain P; et al. (2001). “Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction”. N Engl J Med. 344 (25): 1895–903. doi:10.1056/NEJM200106213442503. PMID 11419426. Review in: ACP J Club. 2002 May-Jun;136(3):89
  31. ↑ Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators (1998). “Inhibition of platelet glycoprotein IIb/IIIa with eptifibatide in patients with acute coronary syndromes”. N Engl J Med. 339 (7): 436–43. doi:10.1056/NEJM199808133390704. PMID 9705684.
  32. ↑ Kastrati A, Neumann FJ, Schulz S, Massberg S, Byrne RA, Ferenc M; et al. (2011). “Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction”. N Engl J Med. 365 (21): 1980–9. doi:10.1056/NEJMoa1109596. PMID 22077909.
  33. ↑ 33.0 33.1 33.2 33.3 Kastrati A, Mehilli J, Schühlen H, Dirschinger J, Dotzer F, ten Berg JM; et al. (2004). “A clinical trial of abciximab in elective percutaneous coronary intervention after pretreatment with clopidogrel”. N Engl J Med. 350 (3): 232–8. doi:10.1056/NEJMoa031859. PMID 14724302.
  34. ↑ 34.0 34.1 O’Shea JC, Hafley GE, Greenberg S, Hasselblad V, Lorenz TJ, Kitt MM; et al. (2001). “Platelet glycoprotein IIb/IIIa integrin blockade with eptifibatide in coronary stent intervention: the ESPRIT trial: a randomized controlled trial”. JAMA. 285 (19): 2468–73. doi:10.1001/jama.285.19.2468. PMID 11368699.
  35. ↑ 35.0 35.1 ESPRIT Investigators. Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (2000). “Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial”. Lancet. 356 (9247): 2037–44. doi:10.1016/S0140-6736(00)03400-0. PMID 11145489.
  36. ↑ Dehghani P, Lavoie A, Lavi S, Crawford JJ, Harenberg S, Zimmermann RH; et al. (2017). “Effects of ticagrelor versus clopidogrel on platelet function in fibrinolytic-treated STEMI patients undergoing early PCI”. Am Heart J. 192: 105–112. doi:10.1016/j.ahj.2017.07.013. PMID 28938956.
  37. ↑ Berwanger O, Nicolau JC, Carvalho AC, Jiang L, Goodman SG, Nicholls SJ; et al. (2018). “Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial”. JAMA Cardiol. 3 (5): 391–399. doi:10.1001/jamacardio.2018.0612. PMC 5875327. PMID 29525822.
  38. ↑ 38.0 38.1 Taniuchi M, Kurz HI, Lasala JM (2001). “Randomized comparison of ticlopidine and clopidogrel after intracoronary stent implantation in a broad patient population”. Circulation. 104 (5): 539–43. doi:10.1161/hc3001.093435. PMID 11479250.
  39. ↑ Bellemain-Appaix A, O’Connor SA, Silvain J, Cucherat M, Beygui F, Barthélémy O; et al. (2012). “Association of clopidogrel pretreatment with mortality, cardiovascular events, and major bleeding among patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis”. JAMA. 308 (23): 2507–16. doi:10.1001/jama.2012.50788. PMID 23287889.
  40. ↑ 40.0 40.1 Schömig A, Neumann FJ, Kastrati A, Schühlen H, Blasini R, Hadamitzky M; et al. (1996). “A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents”. N Engl J Med. 334 (17): 1084–9. doi:10.1056/NEJM199604253341702. PMID 8598866.
  41. ↑ 41.0 41.1 Moussa I, Oetgen M, Roubin G, Colombo A, Wang X, Iyer S; et al. (1999). “Effectiveness of clopidogrel and aspirin versus ticlopidine and aspirin in preventing stent thrombosis after coronary stent implantation”. Circulation. 99 (18): 2364–6. doi:10.1161/01.cir.99.18.2364. PMID 10318654.
  42. ↑ Calver AL, Blows LJ, Harmer S, Dawkins KD, Gray HH, Morgan JH; et al. (2000). “Clopidogrel for prevention of major cardiac events after coronary stent implantation: 30-day and 6-month results in patients with smaller stents”. Am Heart J. 140 (3): 483–91. doi:10.1067/mhj.2000.108825. PMID 10966552.
  43. ↑ 43.0 43.1 Müller C, Büttner HJ, Petersen J, Roskamm H (2000). “A randomized comparison of clopidogrel and aspirin versus ticlopidine and aspirin after the placement of coronary-artery stents”. Circulation. 101 (6): 590–3. doi:10.1161/01.cir.101.6.590. PMID 10673248.
  44. ↑ Bertrand ME, Rupprecht HJ, Urban P, Gershlick AH, CLASSICS Investigators (2000). “Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting : the clopidogrel aspirin stent international cooperative study (CLASSICS)”. Circulation. 102 (6): 624–9. doi:10.1161/01.cir.102.6.624. PMID 10931801.
  45. ↑ Stone GW, Maehara A, Witzenbichler B, Godlewski J, Parise H, Dambrink JH; et al. (2012). “Intracoronary abciximab and aspiration thrombectomy in patients with large anterior myocardial infarction: the INFUSE-AMI randomized trial”. JAMA. 307 (17): 1817–26. doi:10.1001/jama.2012.421. PMID 22447888.
  46. ↑ 46.0 46.1 46.2 Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, Hollenberg SM, Khot UN, Lange RA, Mauri L, Mehran R, Moussa ID, Mukherjee D, Nallamothu BK, Ting HH (2011). “2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions” (PDF). Journal of the American College of Cardiology. 58 (24): 2550–83. doi:10.1016/j.jacc.2011.08.006. PMID 22070837. Retrieved 2011-12-08. Text “PDF” ignored (help); Unknown parameter |month= ignored (help)
  47. ↑ 47.0 47.1 47.2 47.3 47.4 Gurbel PA, Bliden KP, Zaman KA, Yoho JA, Hayes KM, Tantry US (2005). “Clopidogrel loading with eptifibatide to arrest the reactivity of platelets: results of the Clopidogrel Loading With Eptifibatide to Arrest the Reactivity of Platelets (CLEAR PLATELETS) study”. Circulation. 111 (9): 1153–9. doi:10.1161/01.CIR.0000157138.02645.11. PMID 15738352. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  48. ↑ 48.0 48.1 48.2 48.3 48.4 van der Heijden DJ, Westendorp IC, Riezebos RK, Kiemeneij F, Slagboom T, van der Wieken LR, Laarman GJ (2004). “Lack of efficacy of clopidogrel pre-treatment in the prevention of myocardial damage after elective stent implantation”. Journal of the American College of Cardiology. 44 (1): 20–4. doi:10.1016/j.jacc.2004.02.056. PMID 15234399. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  49. ↑ 49.0 49.1 Barnathan ES, Schwartz JS, Taylor L, Laskey WK, Kleaveland JP, Kussmaul WG, Hirshfeld JW (1987). “Aspirin and dipyridamole in the prevention of acute coronary thrombosis complicating coronary angioplasty”. Circulation. 76 (1): 125–34. PMID 2954724. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  50. ↑ 50.0 50.1 Popma JJ, Berger P, Ohman EM, Harrington RA, Grines C, Weitz JI (2004). “Antithrombotic therapy during percutaneous coronary intervention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy”. Chest. 126 (3 Suppl): 576S–599S. doi:10.1378/chest.126.3_suppl.576S. PMID 15383485. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  51. ↑ Smith SC, Allen J, Blair SN, Bonow RO, Brass LM, Fonarow GC, Grundy SM, Hiratzka L, Jones D, Krumholz HM, Mosca L, Pasternak RC, Pearson T, Pfeffer MA, Taubert KA (2006). “AHA/ACC guidelines for secondary prevention for patients with coronary and other atherosclerotic vascular disease: 2006 update: endorsed by the National Heart, Lung, and Blood Institute”. Circulation. 113 (19): 2363–72. doi:10.1161/CIRCULATIONAHA.106.174516. PMID 16702489. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  52. ↑ Chen ZM, Jiang LX, Chen YP, Xie JX, Pan HC, Peto R, Collins R, Liu LS (2005). “Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial”. Lancet. 366 (9497): 1607–21. doi:10.1016/S0140-6736(05)67660-X. PMID 16271642. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  53. ↑ 53.0 53.1 53.2 53.3 Grines CL, Bonow RO, Casey DE, Gardner TJ, Lockhart PB, Moliterno DJ, O’Gara P, Whitlow P (2007). “Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians”. Journal of the American College of Cardiology. 49 (6): 734–9. doi:10.1016/j.jacc.2007.01.003. PMID 17291948. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  54. ↑ Brar SS, Kim J, Brar SK, Zadegan R, Ree M, Liu IL, Mansukhani P, Aharonian V, Hyett R, Shen AY (2008). “Long-term outcomes by clopidogrel duration and stent type in a diabetic population with de novo coronary artery lesions”. Journal of the American College of Cardiology. 51 (23): 2220–7. doi:10.1016/j.jacc.2008.01.063. PMID 18534267. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  55. ↑ Eisenstein EL, Anstrom KJ, Kong DF, Shaw LK, Tuttle RH, Mark DB, Kramer JM, Harrington RA, Matchar DB, Kandzari DE, Peterson ED, Schulman KA, Califf RM (2007). “Clopidogrel use and long-term clinical outcomes after drug-eluting stent implantation”. JAMA : the Journal of the American Medical Association. 297 (2): 159–68. doi:10.1001/jama.297.2.joc60179. PMID 17148711. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  56. ↑ Patrono C, Baigent C, Hirsh J, Roth G (2008). “Antiplatelet drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)”. Chest. 133 (6 Suppl): 199S–233S. doi:10.1378/chest.08-0672. PMID 18574266. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  57. ↑ Steinhubl SR, Bhatt DL, Brennan DM, Montalescot G, Hankey GJ, Eikelboom JW, Berger PB, Topol EJ (2009). “Aspirin to prevent cardiovascular disease: the association of aspirin dose and clopidogrel with thrombosis and bleeding”. Annals of Internal Medicine. 150 (6): 379–86. PMID 19293071. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  58. ↑ Peters RJ, Mehta SR, Fox KA, Zhao F, Lewis BS, Kopecky SL, Diaz R, Commerford PJ, Valentin V, Yusuf S (2003). “Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study”. Circulation. 108 (14): 1682–7. doi:10.1161/01.CIR.0000091201.39590.CB. PMID 14504182. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  59. ↑ Mauri L, Hsieh WH, Massaro JM, Ho KK, D’Agostino R, Cutlip DE (2007). “Stent thrombosis in randomized clinical trials of drug-eluting stents”. The New England Journal of Medicine. 356 (10): 1020–9. doi:10.1056/NEJMoa067731. PMID 17296821. Retrieved 2011-12-06. Unknown parameter |month= ignored (help)
  60. ↑ McFadden EP, Stabile E, Regar E, Cheneau E, Ong AT, Kinnaird T, Suddath WO, Weissman NJ, Torguson R, Kent KM, Pichard AD, Satler LF, Waksman R, Serruys PW (2004). “Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy”. Lancet. 364 (9444): 1519–21. doi:10.1016/S0140-6736(04)17275-9. PMID 15500897. Retrieved 2011-12-06.

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