Chronic stable angina revascularization adjunctive pharmacotherapy for percutaneous coronary intervention

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Lakshmi Gopalakrishnan, M.B.B.S. PTD

Adjunctive Pharmacotheraphy

Vasodilators

  • Nitroglycerine a coronary vasodilator, increases the sub-endocardial perfusion secondary to enhancement of the coronary collateral flow. Hence, prophylactic intracoronary nitroglycerine may be used not only to reduce the risk of vasospasm and vasospastic reactions during PCI but also helps to assess the true vessel diameter.[1]

No Reflow Phenomenon during PCI

  • Selective intracoronary administration of a direct nitric oxide donor such as nitroprusside prior to PCI has also shown to be safe and effective in the treatment of no reflow phenomenon associated with PCI, and has shown to improve myocardial perfusion.[5][6][7]
  • A combination of adenosine and nitroprusside has shown to provide better improvement in the coronary flow in comparison to the use of intracoronary adenosine alone.[8]

Antiplatelet Therapy to Support PCI

Aspirin

  • In the M-HEART II trial (1995), 752 patients were randomized to receive aspirin (a nonselective thromboxane A2 synthesis inhibitor), sulotroban (a selective thromboxane A2 receptor blocker) or a placebo that was started 6 hours before and continued for 6 months after PCI, to evaluate the effects antiplatelet agents on the late clinical events and restenosis after PCI. At 6-month follow-up, aspirin was reported to significantly improve the clinical outcome in comparison to placebo (p=0.46) and sulotroban (p=0.006). The incidence of myocardial infarction was also significantly reduced with the administration of antithromboxane therapy from 5.7% in the placebo group to 1.2% in the aspirin group (p=0.030). However, the rate of restenosis did not significantly differ among the three groups: 39% in the aspirin group, 43% in the placebo group and 53% in the sulotroban group. Thus, the study concluded anti-thromboxane therapy is beneficial to reduce the ischemic complications related to PCI; in particular, aspirin if continued at least for 6 months after coronary angioplasty significantly reduced the incidence of MI and improved the overall clinical outcome.[9]
  • In the meta-analysis (2002) from Antiplatelet Trialists’ Collaboration, 287 randomized trials involving 135000 patients were randomized to receive either antiplatelet therapy or control and 77000 were randomized to different antiplatelet regimens, to determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. The absolute reduction in the risk of having a serious vascular event was 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 36 (SE 6) per 1000 treated for two years among those with previous stroke; 9 (SE 3) per 1000 treated for three weeks among those with acute stroke; and 22 (SE 3) per 1000 treated for two years among other high risk patients with separately significant results for those with stable angina (p=0.0005) and atrial fibrillation (p=0.01). In each of these high risk categories, the absolute benefits of aspirin substantially outweighed the absolute risks of major extracranial bleeding. Among patients at high risk of immediate coronary occlusion, addition of a intravenous glycoprotein IIb/IIIa inhibitor to aspirin for a short period, prevented a further 20 (SE 4) vascular events per 1000 (p=less than 0.0001) but caused 23 major extracranial bleeds per 1000. Thus, the study concluded aspirin at a dose of 75-150 mg/day, has shown reduced mortality and the incidence of vascular events among all high-risk patients including patients with previous or acute MI, unstable or stable angina.[10]

2016 ACC/AHA Guideline focused update on duration of dual antiplatelet therapy (DAPT) in Patients with coronary artery disease

Recommendations for duration of DAPT in patients with SIHD treated with PCI

Class I
"1. In patients with SIHD treated with DAPT after BMS implantation, P2Y12 inhibitor therapy (clopidogrel) should be given for a minimum of 1 month(Level of Evidence: A)"
"2. In patients with SIHD treated with DAPT after DES implantation, P2Y12 inhibitor therapy (clopidogrel) should be given for at least 6 months(Level of Evidence: B-R)"
"3. In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 100 mg) is recommended(Level of Evidence: B-NR)"
Class IIb
"1. In patients with SIHD treated with DAPT after BMS or DES implantation who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk (e.g., prior bleeding on DAPT, coagulopathy, oral anticoagulant use), continuation of DAPT with clopidogrel for longer than 1 month in patients treated with BMS or longer than 6 months in patients treated with DES may be reasonable (Level of Evidence: A)"
"2. In patients with SIHD treated with DAPT after DES implantation who develop a high risk of bleeding (e.g., treatment with oral anticoagulant therapy), are at high risk of severe bleeding complication (e.g., major intracranial surgery), or develop significant overt bleeding, discontinuation of P2Y12 inhibitor therapy after 3 months may be reasonable (Level of Evidence: C-LD)"
"3. In patients with SIHD being treated with DAPT for an MI that occurred 1 to 3 years earlier who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk (e.g., prior bleeding on DAPT, coagulopathy, oral anticoagulant use), further continuation of DAPT may be reasonable (Level of Evidence: A)"
Class III (No Benefit)
"1. In patients with SIHD without prior history of ACS, coronary stent implantation, or recent (within 12 months) CABG, treatment with DAPT is not beneficia (Level of Evidence: B-R)"

ACCF/AHA 2012 Guidelines for the management of SIHD(DO NOT EDIT)[11][12]

Dual Antiplatelet Therapy Compliance and Stent Thrombosis (DO NOT EDIT)[11][12]

Class III (Harm)

"1. PCI with coronary stenting (bare-metal stent or drug-eluting stent) should not be performed if the patient is not likely to be able to tolerate and comply with dual antiplatelet therapy for the appropriate duration of treatment based on the type of stent implanted.[11] [13][14][15][16](Level of Evidence: B)"

ACCF/AHA/SCAI 2011 Guideline for Percutaneous Coronary Intervention (DO NOT EDIT)[12]

No-Reflow Pharmacological Therapies (DO NOT EDIT)[12]

Class IIa
"1. Administration of an intracoronary vasodilator (adenosine, calcium channel blocker, or nitroprusside) is reasonable to treat PCI-related

no-reflow that occurs during primary or elective PCI.[17][18][8][19][5][20][21][22][23][24][25][26][27][28][29][30] (Level of Evidence: B)"

Oral Antiplatelet Therapy (DO NOT EDIT)[12]

Class I
"1. Patients already taking daily aspirin therapy should take 81 mg to 325 mg before PCI.[31][32][33] (Level of Evidence: B)"
"2. Patients not on aspirin therapy should be given non-enteric aspirin 325 mg before PCI.[31][33] (Level of Evidence: B)"
"3. After PCI, use of aspirin should be continued indefinitely.[34][10][35][36] (Level of Evidence: A)"
"4. A loading dose of a P2Y12 receptor inhibitor should be given to patients undergoing PCI with stenting.[37][38][39][40][41] (Level of Evidence: A) Options include:
a. Clopidogrel 600 mg (ACS and non-ACS patients).[37][38][39](Level of Evidence: B)
b. Prasugrel 60 mg (ACS patients).[40] (Level of Evidence: B)
c. Ticagrelor 180 mg (ACS patients).[41] (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.[38][42] (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.[13] (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 [43],prasugrel 10 mg daily [40], and ticagrelor 90 mg twice daily.[41] (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.[13][44][45] (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).[13][46] (Level of Evidence: B)"
Class III (Harm)
"1. Prasugrel should not be administered to patients with a prior history of stroke ortransient ischemic attack.[40] (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.[32][47][48][49][50] (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.[40][41] (Level of Evidence: C)"

References

  1. ↑ Silber S, Albertsson P, Avilés FF, Camici PG, Colombo A, Hamm C et al. (2005) Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J 26 (8):804-47. DOI:10.1093/eurheartj/ehi138 PMID: 15769784
  2. ↑ Tanzilli G, Greco C, Pasceri V, Pelliccia F, Arrivi A, Placanica A et al. (2010) Dipyridamole versus verapamil for treatment of no-reflow during primary angioplasty. Catheter Cardiovasc Interv 76 (6):787-93. DOI:10.1002/ccd.22724 PMID: 20737584
  3. ↑ Ozdemir M, Cemri M, Yalçin R, Cengel A (2001) Use of intracoronary adenosine for the management of slow-no-reflow phenomenon during percutaneous interventions. Catheter Cardiovasc Interv 54 (2):267-8. PMID: 11590698
  4. ↑ Schwartz BG, Kloner RA (2011) Coronary no reflow. J Mol Cell Cardiol ():. DOI:10.1016/j.yjmcc.2011.06.009 PMID: 21712046
  5. ↑ 5.0 5.1 Hillegass WB, Dean NA, Liao L, Rhinehart RG, Myers PR (2001) Treatment of no-reflow and impaired flow with the nitric oxide donor nitroprusside following percutaneous coronary interventions: initial human clinical experience. J Am Coll Cardiol 37 (5):1335-43. PMID: 11300444
  6. ↑ Wang HJ, Lo PH, Lin JJ, Lee H, Hung JS (2004) Treatment of slow/no-reflow phenomenon with intracoronary nitroprusside injection in primary coronary intervention for acute myocardial infarction. Catheter Cardiovasc Interv 63 (2):171-6. DOI:10.1002/ccd.20149 PMID: 15390241
  7. ↑ Shinozaki N, Ichinose H, Yahikozawa K, Shimada H, Hoshino K (2007) Selective intracoronary administration of nitroprusside before balloon dilatation prevents slow reflow during percutaneous coronary intervention in patients with acute myocardial infarction. Int Heart J 48 (4):423-33. PMID: 17827814
  8. ↑ 8.0 8.1 Barcin C, Denktas AE, Lennon RJ, Hammes L, Higano ST, Holmes DR et al. (2004) Comparison of combination therapy of adenosine and nitroprusside with adenosine alone in the treatment of angiographic no-reflow phenomenon. Catheter Cardiovasc Interv 61 (4):484-91. DOI:10.1002/ccd.20010 PMID: 15065143
  9. ↑ Savage MP, Goldberg S, Bove AA, Deutsch E, Vetrovec G, Macdonald RG et al. (1995) Effect of thromboxane A2 blockade on clinical outcome and restenosis after successful coronary angioplasty. Multi-Hospital Eastern Atlantic Restenosis Trial (M-HEART II) Circulation 92 (11):3194-200. PMID: 7586303
  10. ↑ 10.0 10.1 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. PMID: 11786451
  11. ↑ 11.0 11.1 11.2 Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP; et al. (2012). "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons". Circulation. 126 (25): 3097–137. doi:10.1161/CIR.0b013e3182776f83. PMID 23166210.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 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)
  13. ↑ 13.0 13.1 13.2 13.3 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 2011-12-06. Unknown parameter |month= ignored (help)
  14. ↑ Leon MB, Baim DS, Popma JJ, Gordon PC, Cutlip DE, Ho KK, Giambartolomei A, Diver DJ, Lasorda DM, Williams DO, Pocock SJ, Kuntz RE (1998). "A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators". The New England Journal of Medicine. 339 (23): 1665–71. doi:10.1056/NEJM199812033392303. PMID 9834303. Retrieved 2011-12-06. Unknown parameter |month= ignored (help)
  15. ↑ 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)
  16. ↑ 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.
  17. ↑ Amit G, Cafri C, Yaroslavtsev S, Fuchs S, Paltiel O, Abu-Ful A, Weinstein JM, Wolak A, Ilia R, Zahger D (2006). "Intracoronary nitroprusside for the prevention of the no-reflow phenomenon after primary percutaneous coronary intervention in acute myocardial infarction. A randomized, double-blind, placebo-controlled clinical trial". American Heart Journal. 152 (5): 887.e9–14. doi:10.1016/j.ahj.2006.05.010. PMID 17070151. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  18. ↑ Assali AR, Sdringola S, Ghani M, Denkats AE, Yepes A, Hanna GP, Schroth G, Fujise K, Anderson HV, Smalling RW, Rosales OR (2000). <27::AID-CCD7>3.0.CO;2-0 "Intracoronary adenosine administered during percutaneous intervention in acute myocardial infarction and reduction in the incidence of "no reflow" phenomenon". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 51 (1): 27–31, discussion 32. PMID 10973014. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  19. ↑ Fischell TA, Haller S, Pulukurthy S, Virk IS (2008). "Nicardipine and adenosine "flush cocktail" to prevent no-reflow during rotational atherectomy". Cardiovascular Revascularization Medicine : Including Molecular Interventions. 9 (4): 224–8. doi:10.1016/j.carrev.2008.03.002. PMID 18928946. Retrieved 2011-12-15.
  20. ↑ Huang RI, Patel P, Walinsky P, Fischman DL, Ogilby JD, Awar M, Frankil C, Savage MP (2006). "Efficacy of intracoronary nicardipine in the treatment of no-reflow during percutaneous coronary intervention". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 68 (5): 671–6. doi:10.1002/ccd.20885. PMID 17034064. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  21. ↑ Ito H, Taniyama Y, Iwakura K, Nishikawa N, Masuyama T, Kuzuya T, Hori M, Higashino Y, Fujii K, Minamino T (1999). "Intravenous nicorandil can preserve microvascular integrity and myocardial viability in patients with reperfused anterior wall myocardial infarction". Journal of the American College of Cardiology. 33 (3): 654–60. PMID 10080465. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  22. ↑ Kaplan BM, Benzuly KH, Kinn JW, Bowers TR, Tilli FV, Grines CL, O'Neill WW, Safian RD (1996). "Treatment of no-reflow in degenerated saphenous vein graft interventions: comparison of intracoronary verapamil and nitroglycerin". Catheterization and Cardiovascular Diagnosis. 39 (2): 113–8. doi:10.1002/(SICI)1097-0304(199610)39:2<113::AID-CCD1>3.0.CO;2-I. PMID 8922307. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  23. ↑ Marzilli M, Orsini E, Marraccini P, Testa R (2000). "Beneficial effects of intracoronary adenosine as an adjunct to primary angioplasty in acute myocardial infarction". Circulation. 101 (18): 2154–9. PMID 10801755. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  24. ↑ Ono H, Osanai T, Ishizaka H, Hanada H, Kamada T, Onodera H, Fujita N, Sasaki S, Matsunaga T, Okumura K (2004). "Nicorandil improves cardiac function and clinical outcome in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: role of inhibitory effect on reactive oxygen species formation". American Heart Journal. 148 (4): E15. doi:10.1016/j.ahj.2004.05.014. PMID 15459610. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  25. ↑ Piana RN, Paik GY, Moscucci M, Cohen DJ, Gibson CM, Kugelmass AD, Carrozza JP, Kuntz RE, Baim DS (1994). "Incidence and treatment of 'no-reflow' after percutaneous coronary intervention". Circulation. 89 (6): 2514–8. PMID 8205658. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  26. ↑ Ross AM, Gibbons RJ, Stone GW, Kloner RA, Alexander RW (2005). "A randomized, double-blinded, placebo-controlled multicenter trial of adenosine as an adjunct to reperfusion in the treatment of acute myocardial infarction (AMISTAD-II)". Journal of the American College of Cardiology. 45 (11): 1775–80. doi:10.1016/j.jacc.2005.02.061. PMID 15936605. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  27. ↑ Sdringola S, Assali A, Ghani M, Yepes A, Rosales O, Schroth GW, Fujise K, Anderson HV, Smalling RW (2000). <394::AID-CCD4>3.0.CO;2-G "Adenosine use during aortocoronary vein graft interventions reverses but does not prevent the slow-no reflow phenomenon". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 51 (4): 394–9. PMID 11108667. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  28. ↑ Stoel MG, Marques KM, de Cock CC, Bronzwaer JG, von Birgelen C, Zijlstra F (2008). "High dose adenosine for suboptimal myocardial reperfusion after primary PCI: A randomized placebo-controlled pilot study". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 71 (3): 283–9. doi:10.1002/ccd.21334. PMID 17985384. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  29. ↑ Werner GS, Lang K, Kuehnert H, Figulla HR (2002). "Intracoronary verapamil for reversal of no-reflow during coronary angioplasty for acute myocardial infarction". Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions. 57 (4): 444–51. doi:10.1002/ccd.10375. PMID 12455077. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  30. ↑ Weyrens FJ, Mooney J, Lesser J, Mooney MR (1995). "Intracoronary diltiazem for microvascular spasm after interventional therapy". The American Journal of Cardiology. 75 (12): 849–50. PMID 7717298. Retrieved 2011-12-15. Unknown parameter |month= ignored (help)
  31. ↑ 31.0 31.1 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)
  32. ↑ 32.0 32.1 Jolly SS, Pogue J, Haladyn K, Peters RJ, Fox KA, Avezum A, Gersh BJ, Rupprecht HJ, Yusuf S, Mehta SR (2009). "Effects of aspirin dose on ischaemic events and bleeding after percutaneous coronary intervention: insights from the PCI-CURE study". European Heart Journal. 30 (8): 900–7. doi:10.1093/eurheartj/ehn417. PMID 18819961. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  33. ↑ 33.0 33.1 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)
  34. ↑ Schömig A, Neumann FJ, Kastrati A, Schühlen H, Blasini R, Hadamitzky M, Walter H, Zitzmann-Roth EM, Richardt G, Alt E, Schmitt C, Ulm K (1996). "A randomized comparison of antiplatelet and anticoagulant therapy after the placement of coronary-artery stents". The New England Journal of Medicine. 334 (17): 1084–9. doi:10.1056/NEJM199604253341702. PMID 8598866. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  35. ↑ Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, Patrono C, Roncaglioni MC, Zanchetti A (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. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  36. ↑ 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)
  37. ↑ 37.0 37.1 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)
  38. ↑ 38.0 38.1 38.2 Sabatine MS, Cannon CP, Gibson CM, López-Sendón JL, Montalescot G, Theroux P, Lewis BS, Murphy SA, McCabe CH, Braunwald E (2005). "Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study". JAMA : the Journal of the American Medical Association. 294 (10): 1224–32. doi:10.1001/jama.294.10.1224. PMID 16143698. Unknown parameter |month= ignored (help); |access-date= requires |url= (help)
  39. ↑ 39.0 39.1 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)
  40. ↑ 40.0 40.1 40.2 40.3 40.4 Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, Neumann FJ, Ardissino D, De Servi S, Murphy SA, Riesmeyer J, Weerakkody G, Gibson CM, Antman EM (2007). "Prasugrel versus clopidogrel in patients with acute coronary syndromes". The New England Journal of Medicine. 357 (20): 2001–15. doi:10.1056/NEJMoa0706482. PMID 17982182. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  41. ↑ 41.0 41.1 41.2 41.3 Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, Horrow J, Husted S, James S, Katus H, Mahaffey KW, Scirica BM, Skene A, Steg PG, Storey RF, Harrington RA, Freij A, Thorsén M (2009). "Ticagrelor versus clopidogrel in patients with acute coronary syndromes". The New England Journal of Medicine. 361 (11): 1045–57. doi:10.1056/NEJMoa0904327. PMID 19717846. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  42. ↑ 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)
  43. ↑ Mehta SR, Yusuf S, Peters RJ, Bertrand ME, Lewis BS, Natarajan MK, Malmberg K, Rupprecht H, Zhao F, Chrolavicius S, Copland I, Fox KA (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. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  44. ↑ 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)
  45. ↑ 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)
  46. ↑ Steinhubl SR, Berger PB, Mann JT, Fry ET, DeLago A, Wilmer C, Topol EJ (2002). "Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial". JAMA : the Journal of the American Medical Association. 288 (19): 2411–20. PMID 12435254. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  47. ↑ 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)
  48. ↑ 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)
  49. ↑ Serebruany VL, Steinhubl SR, Berger PB, Malinin AI, Baggish JS, Bhatt DL, Topol EJ (2005). "Analysis of risk of bleeding complications after different doses of aspirin in 192,036 patients enrolled in 31 randomized controlled trials". The American Journal of Cardiology. 95 (10): 1218–22. doi:10.1016/j.amjcard.2005.01.049. PMID 15877994. Retrieved 2011-12-13. Unknown parameter |month= ignored (help)
  50. ↑ 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)


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