The Unremitting Advances in STEMI Care and PCI

Updated:Jun 4,2014

The Unremitting Advances in STEMI Care and PCI

Disclosure: None.
Pub Date: Wednesday, November 18, 2009
Author: Hani Jneid, MD


Kushner FG, Hand M, Smith SC Jr, et al. 2009 Focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009. Published online before print, November 18, 2009. 10.1161/CIRCULATIONAHA.109.192663.

Article Text

Ischemic heart disease remains the leading cause of mortality in the Western world. In particular, coronary artery disease (CAD) claims one of every five deaths in the United States and nearly one American suffers an acute ST-segment elevation myocardial infarction (STEMI) every minute.[1,2] Primary percutaneous coronary intervention (PCI) is the mainstay initial therapy for STEMI.[3] It is, thus, not unexpected that a synopsis of the advances in both fields are published jointly, as in the current report.[4] The 2009 Focused Updates of the guidelines on PCI for the management of patients with STEMI [4], a result of the collaborative efforts of the American Heart Association (AHA), American College of Cardiology Foundation (ACC), and Society for Cardiovascular Angiography and Interventions (SCAI), considered a plethora of studies and generated updated, well-balanced, and clinically-applicable recommendations.[4] In this report, I provide a noncomprehensive synopsis of these recommendations and a critical reading of the associated evidence.

Prasugrel, a more potent and rapid-acting thienopyridine than clopidogrel, was incorporated in the current report [4] following the release of TRITON-TIMI 38 [5] and its subsequent Food and Drug Administration approval (July 2009). TRITON-TIMI 38 [5] was a pivotal randomized controlled trial (RCT) of 13,608 patients demonstrating a significant 19% reduction in the composite of cardiovascular death, myocardial infarction (MI), or stroke with prasugrel (60-mg loading followed by10-mg daily doses) compared with clopidogrel after a mean 15-months follow-up. This salubrious outcome, driven by a reduction in nonfatal MI, was observed as early as 3 days postrandomization, and was accompanied by notable reductions in the rates of ischemic events, urgent target vessel revascularization (TVR), and stent thrombosis (ST) in the prasugrel group.[5] Despite an overall 32% increase in major bleeding with prasugrel (including thrombolysis in myocardial infarction (TIMI) major and life-threatening bleeding), the net clinical-benefit end point still favored prasugrel.[5] Notably, stronger benefits were observed in high-risk patients, such as diabetics [5] and patients with anterior STEMI.[6] The 2009 Focused Update [4], therefore, recommends the addition of prasugrel as an alternative choice to clopidogrel during primary PCI but cautioned against its use in those with a history of stroke or transient ischemic attack, as shown previously [7], and recommended its empiric discontinuation at least 7 days before planned CABG.[5] TRITON-TIMI 38 enrolled moderate-to high-risk ACS patients scheduled to undergo PCI, of whom 26% had STEMI, and therefore did not apply to all ACS patients.[5] The need for thienopyridine discontinuation before CABG may prevent the widespread adoption of prasugrel in the community, especially knowing the coronary anatomy (less relevant in patients undergoing primary PCI [5]), but may be overcome by the progressive adoption of platelet function testing to determine the degree of platelet inhibition and predict the timing of safe CABG surgery.[8] Post-hoc analyses from TRITON-TIMI 38 [5] identified two additional subgroups in whom prasugrel had no net favorable clinical benefit (patients greater than or equal to 75 years old and those who weighed less than 60 kg).[5] It is also important to note that the comparator group was treated with the conventional 300-mg loading dose of clopidogrel [9,10], which achieves a slower peak effect, compared with a 600-mg loading dose, and which has been recently shown to be inferior to the upfront clopidogrel double-dosing regimen in the CURRENT-OASIS 7 trial.[11]

The 2009 Focused Update [4] provides a review of the evidence pertaining to the timing of GP IIb/IIIa inhibitors and their comparative effectiveness. They concluded that the use of intravenous glycoprotein (GP) IIb/IIIa receptor inhibitors at the time of primary PCI can no longer be routinely recommended [12-14] and should be substituted with a more selective approach (as in the setting of a large thrombus burden or no thienopyridine pretreatment). In addition, the routine upstream use of GP IIb/IIIa inhibitors, as a facilitated approach prior to cath lab arrival for primary PCI [12,15] or in non-ST elevation acute coronary syndrome (NSTE-ACS) patients undergoing early angiography [16], is no longer recommended given the absence of benefits on ischemic end points [12,15,16] and the increased bleeding risk.[16,17] Among patients with NSTE-ACS, upstream use of GP IIb/IIIa inhibitors may be beneficial in diabetics, patients with elevated biomarker levels, patients more than 75 years old, and those undergoing PCI. These patient subgroups, identified on post-hoc analyses from EARLY-ACS [16], were previously confirmed by prior evidence.[18] Newer data demonstrated similar efficacy of the small molecules (tirofiban or eptifibatide) and the chimeric monoclonal antibody abciximab in the setting of primary PCI.[19-21] The salutary outcomes associated with GP IIb/IIIa inhibitors in prior trials were predominantly driven by periprocedural MI reduction and appear to be attenuated nowadays by optimal background medical treatments (ex. statin, dual oral antiplatelet therapy, better anticoagulants), early invasive and timely reperfusion strategies, and better interventional techniques. In addition, the realization of the importance of including periprocedural bleeding in the assessment of outcomes after PCI [22] has diminished the net clinical benefits previously observed with GP IIb/IIIa inhibitors.

Along these lines, the use of the direct thrombin inhibitor, bivalirudin, during primary PCI has been adopted as an alternative to the combination of unfractionated heparin and GP IIb/IIIa inhibitors during primary PCI (on top of background dual oral antiplatelet therapy).[4] This was derived from the landmark HORIZONS-AMI [14], a RCT of 3,602 STEMI patients undergoing primary PCI, demonstrating a lower incidence of net adverse clinical events at 30 days and 1 year with bivalirudin use (driven largely by a decrease in major bleeding).[14,23] Bivalirudin was associated with remarkably lower 30-day [14] and 1-year all-cause mortality rates [23], which was attributable to the greater contribution of major bleeding to mortality than reinfarction or ST, as shown by others.[22] The salutary benefits of bivalirudin was unaffected by the use of preprocedural heparin or higher clopidogrel loading dose [14], although both predicted the occurrence of early ST with bivalirudin.[24] In a 2x2 factorial design, HORIZONS-AMI [25] examined the use of the first-generation paclitaxel-eluting stent (a drug-eluting stent, DES) versus its bare-metal stent (BMS) counterpart during primary PCI for STEMI and demonstrated no intergroup differences in 12-month rates of mortality, MI, or ST, but a small reduction in TVR and in 13-month binary restenosis (hence, TVR was unaffected by angiographic follow-up). The safety and efficacy of DESs in the STEMI setting were also supported by a meta-analysis, including 3,605 patients from 11 trials, showing no difference in major adverse cardiovascular events, including ST, at 12-months follow-up and a significant reduction in TVR up to 24-months follow-up.[26] The use of DESs is therefore endorsed as a reasonable alternative strategy to BMSs. However, the 2009 Focused Update [4] judiciously emphasized that stent use during primary PCI should take into consideration patients' compliance, concomitant use of oral anticoagulation, and the possible need for surgery during the ensuing year. Recently, the 2-year data from HORIZONS-AMI confirmed the persistent benefits of bivalirudin and DESs.[27]

Another important guideline update pertains to PCI for left main (LM) CAD.[4] The SYNTAX trial [28] assessed the optimal revascularization strategy in 1,800 patients with previously untreated three-vessel or LM CAD and found the PCI strategy (using paclitaxel-eluting stents) not to be noninferior to CABG with respect to the 12-month primary composite of major adverse cardiac or cerebrovascular events (MACCEs). This was driven by higher rates of repeat revascularization associated with PCI, although no differences in death or MI rates were observed and a small but significantly higher stroke rate was evident with CABG.[28] The higher MACCEs rates associated with PCI were observed in patients in the highest SYNTAX scores and in those with two- and three-vessel CAD (the latter being a post-hoc finding that should be interpreted with caution).[28] The 2-year follow-up data from SYNTAX [29] confirmed its earlier findings but further uncovered a significantly higher MI rate with PCI during this time period. Despite the all-comers design of SYNTAX, its applicability to routine clinical practice remains uncertain, given the inclusion of seasoned interventional cardiologists treating complex CAD (4.3 treated lesions/patient, 73% bifurcation, and one-third had a greater than 100 mm stent length).[28] Patients treated with CABG also received suboptimal postrevascularization, which may bias the outcomes.[28] Although CABG continues as the standard therapy for complex multivessel and/or LM CAD, PCI for LM CAD may be considered instead of CABG in patients with suitable coronary anatomy and/or high surgical risk. In the absence of supporting evidence, a 2-to 6-month angiographic follow-up after LM stenting is no longer recommended.[4]

In addition to the aforementioned recommendations, the current report [4] endorsed a multitude of additional therapeutic strategies. An early invasive strategy (within 12 to 24 hours), but not an immediate invasive one, appears to be reasonable in high-risk NSTE-ACS patients.[30,31] Furthermore, based on the FAME study [32], showing superior 1-year outcomes and less use of stents per patient with the use of fractional flow reserve (FFR), FFR appears to be a reasonable strategy to complement angiography in order to determine the significance of intermediate coronary lesions and guide interventions in patients with stable multivessel CAD. This is especially important given recent reports showing that the majority of such patients do not have preceding noninvasive testing to document ischemia or target therapy.[33] Following the finding in the NICE-SUGAR trial [34], which showed a morbidity benefit from intensive glucose control and a reduction in mortality for those who were in the intensive care unit for more than 3 days, and other studies [35], the 2009 Focused Update [4] also endorsed the use of an insulin-based regimen as a reasonable strategy to achieve and maintain a glucose level less than 180 mg/dL while avoiding hypoglycemia. An earlier AHA statement [36] called urgently for definitive trials to assess the best treatment strategies for glycemic control and define specific treatment targets. In addition, aspiration thrombectomy before PCI was associated with better myocardial reperfusion [37] and lower 1-year cardiac mortality [38] among STEMI patients undergoing primary PCI (on top of optimal medical therapies, including 600-mg clopidogrel loading dose and abciximab). This cheap and readily available technique, which was also associated with infarct size reduction [39], stands in contradistinction to mechanical thrombectomy and embolic protection, which were associated with increased harm or a neutral effect during primary PCI [40], respectively. Therefore, aspiration thrombectomy appears a reasonable strategy during primary PCI.[4] Following the CARE study [41], finding no impact of various contrast media on the rates of contrast-induced nephropathy (CIN), the recommended choices of agents for patients with chronic kidney disease has been expanded to include isosmolar or low-osmolar agents (other than ioxaglate or iohexol).[4]

Overall, Kushner and colleagues are to be congratulated on their efforts to critically evaluate the evidence and produce useful recommendations to guide clinicians. One can derive innumerable and noteworthy observations from their report.[4] Notably, the contemporary 12- to15-months MACE rates following STEMI are in the range of 12% [5,23], which speak for the alarming residual burden of morbidity and mortality in these patients. It is reassuring, however, that the 2009 Focused Update [4] reported at least two strategies (bivalirudin use, aspiration thrombectomy) associated with small but significant reductions in mortality. Advances in therapies are therefore rapidly evolving. One should, however, constantly remember that the discovery of new pharmaceuticals and better therapeutic strategies should be accompanied by the adoption of older well-established therapies. The existing disparities in STEMI care [42,43] has been repetitively demonstrated and the chasm described in the Institute of Medicine report between the care we have and the care we could have [44] still applies best for the treatment of STEMI. Finally, while 47% of the decline in CAD mortality observed in this country since 1986 is attributable to treatments, only 10% are related to immediate therapies after ACS [1], which account for the majority of the recommendations in the current report. Secondary-prevention therapies along with lifestyle changes and risk-factor modification continue to impart the highest impact and are largely lacking.[1]


  1. Lloyd-Jones D, Adams R, Carnethon M, et al. Heart disease and stroke statistics--2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119(3):480-486.
  2. Roe MT, Parsons LS, Pollack CV Jr, et al. Quality of care by classification of myocardial infarction: treatment patterns for ST-segment elevation vs non-ST-segment elevation myocardial infarction. Arch Intern Med 2005;165(14):1630-1636.
  3. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003;361(9351):13-20.
  4. Kushner FG, Hand M, Smith SC Jr, et al. 2009 Focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2009. Published online before print, November 18, 2009. 10.1161/CIRCULATIONAHA.109.192663.
  5. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357(20):2001-2015.
  6. Montalescot G, Wiviott SD, Braunwald E, et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet 2009;373(9665):723-731.
  7. Diener HC, Bogousslavsky J, Brass LM, et al. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high-risk patients (MATCH): randomised, double-blind, placebo-controlled trial. Lancet 2004;364(9431):331-337.
  8. Jneid H, Bhatt DL. Advances in antiplatelet therapy. Expert Opin Emerg Drugs 2003;8(2):349-363.
  9. Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005;294(10):1224-1232.
  10. Jneid H, Bhatt DL, Corti R, et al. Aspirin and clopidogrel in acute coronary syndromes: therapeutic insights from the CURE study. Arch Intern Med 2003;163(10):1145-1153.
  11. Mehta SR. Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent EveNTs/Optimal Antiplatelet Strategy for InterventionS: CURRENT-OASIS 7 trial. Available from:
  12. Van't Hof AW, Ten Berg J, Heestermans T, et al. Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial. Lancet 2008;372(9638):537-546.
  13. Mehilli J, Kastrati A, Schulz S, et al. Abciximab in patients with acute ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention after clopidogrel loading: a randomized double-blind trial. Circulation 2009;119(14):1933-1940.
  14. Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008;358(21):2218-2230.
  15. Ellis SG, Tendera M, de Belder MA, et al. Facilitated PCI in patients with ST-elevation myocardial infarction. N Engl J Med 2008;358(21):2205-2217.
  16. Giugliano RP, White JA, Bode C, et al. Early versus delayed, provisional eptifibatide in acute coronary syndromes. N Engl J Med 2009;360(21):2176-2190.
  17. Stone GW, Bertrand ME, Moses JW, et al. Routine upstream initiation vs deferred selective use of glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: the ACUITY Timing trial. JAMA 2007;297(6):591-602.
  18. Boersma E, Harrington RA, Moliterno DJ, et al. Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 2002;359(9302):189-198.
  19. Valgimigli M, Campo G, Percoco G, et al. 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 2008;299(15):1788-1799.
  20. Gurm H, Tamhane U, Meier P, et al. A comparison of abciximab and small molecule glycoprotein IIb/IIIa inhibitors in patients undergoing primary percutaneous coronary intervention: a meta-analysis of contemporary randomized controlled trials. Circ Cardiovasc Intervent 2009;(2):230-236.
  21. De Luca G, Ucci G, Cassetti E, Marino P. Benefits from small molecule administration as compared with abciximab among patients with ST-segment elevation myocardial infarction treated with primary angioplasty: a meta-analysis. J Am Coll Cardiol 2009;53(18):1668-1673.
  22. Ndrepepa G, Berger PB, Mehilli J, et al. Periprocedural bleeding and 1-year outcome after percutaneous coronary interventions: appropriateness of including bleeding as a component of a quadruple end point. J Am Coll Cardiol 2008;51(7):690-697.
  23. Mehran R, Lansky AJ, Witzenbichler B, et al. Bivalirudin in patients undergoing primary angioplasty for acute myocardial infarction (HORIZONS-AMI): 1-year results of a randomised controlled trial. Lancet 2009;374(9696):1149-1159.
  24. Dangas GD. Predictors of stent thrombosis after primary angioplasty in acute myocardial infarction: The HORIZONS-AMI Trial. Available from:
  25. Grines CL, Bonow RO, Casey DE Jr, et al. 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. Circulation 2007;115(6): 813-818.
  26. De Luca G, Stone GW, Syruapranata H, et al. Efficacy and safety of drug-eluting stents in ST-segment elevation myocardial infarction: a meta-analysis of randomized trials. Int J Cardiol 2009;133(2):213-222.
  27. Stone GW. Two-year data from the Harmonizing Outcomes with Revascularization and Stents in AMI (HORIZONS-AMI) trial. Available from:
  28. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360(10):961-972.
  29. Kappetein AP. SYNTAX - Optimal revascularization strategy in patients with three-vessel disease and/or left main disease: The 2 year outcomes of the SYNTAX Trial. Available from:
  30. Mehta SR, Granger CB, Boden WE, et al. Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med 2009;360(21):2165-2175.
  31. Montalescot G, Cayla G, Collet JP, et al. Immediate vs delayed intervention for acute coronary syndromes: a randomized clinical trial. JAMA 2009;302(9):947-954.
  32. Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360(3):213-224.
  33. Lin GA, Dudley RA, Lucas FL, et al. Frequency of stress testing to document ischemia prior to elective percutaneous coronary intervention. JAMA 2008;300(15):1765-1773.
  34. Van den Berghe G, Wilmer A, Hermans G, et al. Intensive insulin therapy in the medical ICU. N Engl J Med 2006;354(5):449-461.
  35. Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA 2008;300(8):933-944.
  36. Deedwania P, Kosiborod M, Barrett E, et al. Hyperglycemia and acute coronary syndrome: a scientific statement from the American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 2008;117(12):1610-1619.
  37. Svilaas T, Vlaar PJ, van der Horst IC, et al. Thrombus aspiration during primary percutaneous coronary intervention. N Engl J Med 2008;358(6):557-567.
  38. Vlaar PJ, Svilaas T, van der Horst IC, et al. Cardiac death and reinfarction after 1 year in the Thrombus Aspiration during Percutaneous coronary intervention in Acute myocardial infarction Study (TAPAS): a 1-year follow-up study. Lancet 2008;371(9628):1915-1920.
  39. Sardella G, Mancone M, Bucciarelli-Ducci C, et al. Thrombus aspiration during primary percutaneous coronary intervention improves myocardial reperfusion and reduces infarct size: the EXPIRA (thrombectomy with export catheter in infarct-related artery during primary percutaneous coronary intervention) prospective, randomized trial. J Am Coll Cardiol 2009;53(4):309-315.
  40. Bavry AA, Kumbhani DJ, Bhatt DL. Role of adjunctive thrombectomy and embolic protection devices in acute myocardial infarction: a comprehensive meta-analysis of randomized trials. Eur Heart J 2008;29(24):2989-3001.
  41. Solomon RJ, Natarajan MK, Doucet S, et al. Cardiac Angiography in Renally Impaired Patients (CARE) study: a randomized double-blind trial of contrast-induced nephropathy in patients with chronic kidney disease. Circulation 2007;115(25):3189-3196.
  42. Jneid H, Fonarow GC, Cannon CP, et al. Impact of time of presentation on the care and outcomes of acute myocardial infarction. Circulation 2008;117(19):2502-2509.
  43. Jneid H, Fonarow GC, Cannon CP, et al. Sex differences in medical care and early death after acute myocardial infarction. Circulation 2008;118(25):2803-2810.
  44. Committee on Quality of Health Care in America, Institute of Medicine. Crossing the Quality Chasm: A New Health System for the 21st Century. Washington, D.C.: National Academy Press, 2001.

-- The opinions expressed in this commentary are not necessarily those of the editors or of the American Heart Association --

AHA Scientific Journals

AHA Scientific Journals

Connect with AHA Science News

Follow AHAScience on Twitter (opens in new window)
Like AHA Science News on Facebook (opens in new window)

Science News View All