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SPCI - Sociedade Portuguesa de Cuidados Intensivos

Revista Brasileira de Terapia Intensiva

AMIB - Associação de Medicina Intensiva Brasileira

OFFICIAL JOURNAL OF THE ASSOCIAÇÃO BRASILEIRA DE MEDICINA INTENSIVA AND THE SOCIEDADE PORTUGUESA DE CUIDADOS INTENSIVOS

ISSN: 0103-507X
Online ISSN: 1982-4335

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Pesaro AEP, Campos PCGD, Katz M, Corrêa TD, Knobel E. Síndromes coronarianas agudas: tratamento e estratificação de risco. Rev Bras Ter Intensiva. 2008;20(2):197-204

 

 

2008;20(2):197-204
Review Article

http://dx.doi.org/10.1590/S0103-507X2008000200014

Acute coronary syndromes: treatment and risk stratification

Síndromes coronarianas agudas: tratamento e estratificação de risco

Antonio Eduardo Pereira PesaroI, Paulo Cesar Gobert Damasceno CamposI, Marcelo KatzI, Thiago Domingos CorrêaII, Elias KnobelIII

IAssistant Physician - Intensive Care Unit Hospital Israelita Albert Einstein
IIMedical Resident - Intensive Care Unit Hospital Israelita Albert Einstein
IIIVice-President of Medical affairs of the Board of Directors and Director Emeritus and Founder of the Intensive Care Unit Hospital Israelita Albert Einstein

Presented in September, 20, 2007
Accepted for publication in April, 10, 2008

Corresponding author:

Antonio Eduardo Pereira Pesaro, M.D.
Unidade Coronariana - Hospital Israelita Albert Einstein
Av. Albert Einstein, 627, Morumbi
05651-901 São Paulo, SP
Fone: (11) 3747-15003 / Fax: (11) 3742-2834
E-mail: [email protected]

 

Abstract

BACKGROUND AND OBJECTIVES: Acute coronary syndromes result from a disruption of a vulnerable coronary plaque complicated by intraluminal thrombus formation, embolisation, and variable degrees of coronary obstruction. Patients with total occlusion may present with acute ST Elevation Myocardial Infarction (STEMI). Partial vessel obstruction may result in Non-ST-Elevation Acute Myocardial Infarction (NSTEMI) or unstable angina (UA). Clinical symptoms and electrocardiographic changes are the main components of identification of ACS. The rapid and effective triage of such patients regarding presence or absence of ST-segment elevation is critical to dictate further therapeutic strategies. The objective of this chapter was to review current evidence and recommendations for the evaluation and early treatment of acute coronary syndromes.
CONTENTS: We performed a clinical review using the electronic databases MedLine and LILACS from January 1990 to September 2007.
CONCLUSIONS: Reperfusion of the infarct-related artery is the cornerstone of therapy for STEMI. Fibrinolysis and percutaneous coronary intervention are both well established as effective options. Management of UA/NSTEMI patients requires early risk stratification. High-risk patients should undergo an early invasive strategy that consists in performance of cardiac catheterization in the first 24 to 48 hours of presentation.

Keywords: acute coronary syndromes, Non-ST elevation acute coronary syndrome, myocardial infarction, percutaneous coronary intervention, reperfusion treatment, risk stratification, ST elevation acute coronary syndrome, unstable angina

 

 

INTRODUCTION

Acute coronary syndromes (ACS) result from a disruption of a vulnerable coronary plaque complicated by intraluminal thrombus formation, embolisation, and variable degrees of coronary obstruction1.

ACS included a spectrum of clinical presentations. Patients with total occlusion may present with acute ST-Elevation Myocardial Infarction (STEMI) requiring emergency reperfusion therapy. Partial vessel obstruction may result in Non-ST Elevation Acute Myocardial Infarction (NSTEMI) or unstable angina (UA), that will require initial medical stabilization followed by judicious risk stratification for determination of therapeutic strategies (invasive or conservative)1.

Ischemic heart disease accounts for nearly 1 million deaths in the United States annually. In industrialized countries, annual incidence of unstable angina is approximately 6 cases per 10,000 people. The overall mortality rates are approximately 30% for acute myocardial infarction (AMI). Half of the deaths occur in the first two hours of the event and 14% of the patients die before receiving medical care2,3.

The purpose of this chapter is to review current evidence and recommendations for the evaluation and early treatment of acute coronary syndromes.

 

DEFINITION AND CLASSIFICATION OF ACUTE CORONARY SYNDROME

Patients without evidence of MI, but with typical ischemic syndrome are classified into the spectrum of UA with the possible following clinical presentations: rest angina, new-onset angina or increased angina pattern4.

The definition of STEMI is a new, or presumed new, ST segment elevation in 2 or more contiguous leads of at least 2 mm at the J point in leads V1-V3, or 1 mm in other leads5.

NSTEMI presentations represent a real diagnostic challenge. In those cases ECG changes may appear as ST segment depression, transient ST elevation or T wave inversion. Differentiation of NSTEMI from UA is based on marker of myocyte necrosis elevation in the former and absence of it in the latter1,4.

 

SPECIFIC TREATMENT FOR ST-ELEVATION MYOCARDIAL INFARCTION

Perfusion

Reperfusion of the infarct-related artery is the cornerstone of therapy for STEMI. Fibrinolysis and percutaneous coronary intervention (PCI) are both well established as effective options, but PCI has generally come to be regarded as the treatment of choice6. It should be performed as soon as possible to minimize myocardial damage. The efficacy in the restoration and maintenance of optimal flow (TIMI 3) are directly related to the prognosis of myocardial infarction7.

A recent meta-analysis of 23 randomized, controlled trials comparing PCI to fibrinolysis revealed that PCI reduced short-term mortality, non-fatal re-infarction, and stroke when compared to fibrinolysis8.

The choice of reperfusion therapy depends on several factors: time delay to primary PCI (door-balloon time), pre-hospital delay, time to hospital fibrinolysis (door-needle time), contraindications and risks of fibrinolytic therapy, location and size of MI, presence of heart failure or cardiogenic shock (high-risk MI). However, the major factor to determine the choice of reperfusion is TIME, including time since symptom onset, time delay for transportation and time delay for primary PCI9.

According to the ACC/AHA 2004 guidelines, it is not possible to say that one modality is superior for all patients in all settings. There is also concern that outcomes achieved with PCI in the setting of clinical trials may not be reproducible in the real world, mainly because randomized controlled trials usually enroll a select group of patients who are cared for by experts in high-volume centers9.

Fibrinolytics

Due to its universal availability, fibrinolysis remains the mainstay of reperfusion therapy. Fibrinolytic therapy given early, within 3 hours after symptom onset, can result in mortality reduction of up to 50%10.

The first fibrinolytic efficiently tested for AMI was streptokinase, showing 18% mortality reduction11. In 1993, the GUSTO 1study demonstrated the superiority of t-PA combined to UFH, over streptokinase, decreasing 30-day mortality rate from 7.2% to 6.3%, with this benefit persisting at one year. T-PA allowed more efficient reperfusion and TIMI grade 3 flows in 54% of the cases12. Since then, other studies with newer, fibrin-specific fibrinolytics, such as reteplase (r-PA) and tenecteplase (TNK), represent a small but significant improvement over the first-generation drugs (i.e., streptokinase and urokinase). These new agents can be administered as bolus injections, minimizing time delay in the pre-hospital and emergency room settings. Of the newest fibrinolytic agents, tenecteplase therapy was found to be complicated by fewer major bleeds and blood transfusions than t-PA (4.66% vs. 5.94%, p = 0.0002; 4.25% vs. 5.49%, p = 0.0002, respectively)13.

In summary, fibrinolysis would be generally preferred for patients with early presentation (< 3 hours from symptom onset), and mainly in the presence of time delay to invasive strategy9.

 

PRE-HOSPITAL FIBRINOLYSIS

In select settings, pre-hospital fibrinolysis appears to offer a mortality advantage over in-hospital administration. A meta-analysis of 6 trials with 6,434 patients found a reduction in all-cause hospital mortality (odds ratio 0.83, 95% CI 0.70 - 0.98) with prehospital fibrinolysis14.

The CAPTIM study randomized patients managed within 6 h of acute STEMI to primary angioplasty or prehospital fibrinolysis (rt-PA) with immediate transfer to a centre with interventional facilities. It found a similar incidence of the primary endpoint of death, recurrent MI, or stroke at 30 days with both strategies15.

 

LIMITATION AND HAZARDS OF FIBRINOLYTIC THERAPY

Unsuccessful reperfusion (absence of TIMI 3 flow with first few hours after fibrinolysis) may range from 40% with use of streptokinase to 20%-30% with newer fibrin specific agents1.

The main hazard remains to be intracerebral bleeding: overall 3.9 strokes per 1,000 patients treated within the first 24h of treatment. Advanced age, female gender, low body weight, hypertension, previous cerebrovascular accident and use of alteplase (r-TPA) constitute risk factors for intracranial hemorrhage1,3,9.

 

PRIMARY PCI, TRANSFER AND RESCUE PCI

In patients with STEMI, primary PCI should be treatment of choice in patients presenting to a hospital with a PCI facility and an experienced team, or in the presence of contra-indications for thrombolytic therapy. In cardiogenic shock, emergency PCI may be life saving and should be considered at an early stage. The superiority of PCI over thrombolysis appears to be relevant for the time interval between 3 and 12 hours after onset of symptoms and in high-risk patients (cardiogenic shock, Killip group > 3), based on its capacity of better preservation of myocardium. Within the first 3 hours of symptoms, both strategies are equally effective in achieving reperfusion, reducing MI size and mortality9.

Trials comparing early (pre-hospital) thrombolysis and transfer to a tertiary center with a PCI facility, observed better clinical outcomes in the group that underwent PCI. However, transfer times caused delays between randomization and start of treatment14,15.

When thrombolysis fails (less than 50% reduction of ST segment and persistent pain) rescue PCI can be useful when performed within 45-60 minutes after starting the infusion.

 

FACILITATED PCI

Despite the attractive rational of early administration of a fibrinolytic agent (usually in a low dose) followed immediately by a more complete mechanical reperfusion by PCI, this strategy has not been able to provide benefit. The recent and early interrupted ASSENT 4 study (TNK facilitated primary PCI vs. primary PCI with Gp IIb/IIIa inhibitor) showed increased number of adverse events in the group of facilitated PCI16. At this moment, there is no recommendation to support this strategy17.

 

ADJUNCTIVE THERAPY FOR STEMI

Anti-platelet agents have proven themselves to be valuable adjuncts to mechanical reperfusion by reducing these early thrombotic complications. Adjunctive therapy is also important following administration of fibrinolytics. It is thought that fibrin-specific agents, while promoting local clot lysis, may actually exert a systemic pro-coagulant effect through increased thrombin activity and possibly via enhanced platelet aggregation18,19.

 

ANTIPLATELET THERAPY FOR STEMI

The ISIS-2 study was the largest trial of aspirin in STEMI; it provides the best evidence that aspirin (ASA) reduces mortality in such patients20. ASA should be administered as soon as possible, in 162 - 325 mg doses and continued indefinitely in a lower maintenance dose of 75 to 162 mg. Clopidogrel or ticlopidine are indicated in the presence of true allergy to aspirin9.

Clopidogrel should be considered in all patients undergoing angioplasty with stent implantation. The Clarity study demonstrated benefits and safety in the use of clopidogrel in patients treated with fibrinolytics and aspirin, showing improved coronary patency by prevention of reocclusion, and decreased adverse event rate21. A 300 mg clopidogrel loading dose, followed by 75 mg/day from 1 to 12 months should be used. Patients treated with stents in the acute setting of MI, should take clopidogrel for up to 1-12 months. Those treated with drug elucting stents must take clopidogrel for a longer period of time (more than 6 months). Some specialists consider the use of clopidogrel for indeterminated time based on recent studies that evaluated the risk of late thrombosis22.

Studies have demonstrated controversial results regarding the use of Gp IIb/IIIa inhibitors in STEM21,23. Angiographic and clinical benefits are possible, mainly in the presence of extensive thrombus or in vascular grafts angioplasties. Two recent studies demonstrated no advantage for combination of a thrombolytic agent and a glycoprotein (Gp) IIb/IIIa inhibitor. In patients over 70 years old there was increased risk of bleeding21,23.

 

ANTICOAGULATION IN STEMI

Benefit of unfractioned heparin lies in the maintenance of coronary stability in the hours and days following fibrinolytic use. It should be combined to t-PA or TNK for 24-48 hours. The use of low molecular weight heparin is an acceptable alternative in patients under 75 years old and normal kidney function. LMWH should not be used as an alternative to UFH as adjunctive therapy in elderly patients (over 75 years) receiving fibrinolysis. Patients at high-risk of systemic emboli (large or anterior MI, atrial fibrillation, previous embolus, or known left ventricle thrombus) should be given intravenous UFH9.

 

OTHER ANCILLARY MEDICATIONS

Beta-blockers are thought to be cardioprotective, reducing infarct size and reinfarction when co-administered with fibrinolytics, and reducing mortality when continued long term after AMI. Oral beta-blockers constitute class I recommendation by the ACC-AHA in the setting of STEMI9. Early IV beta-blockers may be considered in special situations such as tachycardia or hypertension24.

Other medication with class I recommendation are the ACE-inhibitors. These agents limit ventricular dilatation and remodeling by interruption of the rennin-angiotensin-aldosterone system. They should be given orally within the first 24 hours post-infarct to patients who have experienced symptoms of heart failure or those known to have left ventricular systolic dysfunction9.

Angiotensin receptor blocker should be considered as an alternative to ACE-inhibitors in patients with systolic dysfunction (LVEF < 40%) post-MI, as demonstrated by non inferiority of valsartan compared to captopril in the VALIANT study25.

Long term aldosterone blockade for high-risk patients (LVEF < 40%, heart failure, diabetes mellitus) should be considered26.

Current guidelines for patients with established coronary artery disease recommend that the goal of treatment should be an LDL cholesterol level of less than 100 mg/dL4. However, more aggressive lipid lowering (LDL cholesterol less than 70 mg/dL) further lowers cardiovascular event rates and is safe, although the incremental impact on mortality over moderate lipid-lowering remains to be clearly established27.

 

RISK STRATIFICATION AFTER STEMI

Risk stratification of all patients with STEMI begins after the initial event. Patients treated with primary angioplasty may be discharged without additional stratification9. Patients treated with fibrinolytics or with no reperfusion treatment, should be investigated according to table 1.

 

SPECIFIC TREATMENT FOR UA / NSTEMI PATIENTS

Early Risk Stratification

Management of UA/NSTEMI patients requires an early risk stratification to estimate the risk of adverse outcomes (death, infarction, re-infarction, stroke, urgent revascularization and re-hospitalization for ACS). This process is critical to define best therapeutic strategy. Several tools were developed to stratify the risk of these patients: GRACE28, PURSUIT29 and TIMI30 (Table 2) scores and the classification of the American Heart Association/American College of Cardiology31 (Table 3).

 

ADDITIONAL PLATELET AGGREGATION INHIBITORS

Several studies have shown that ASA combined with others platelet inhibitors (thienopyridines and glycoprotein IIb/IIIa receptor inhibitors- iGPIIb/IIIa) are beneficial in patients presenting with ACS.

The CURE trial evaluated the efficacy and safety of the combination of clopidogrel plus ASA in 12,562 patients with UA/NSTEMI32. This association decreased by 20% the risk of adverse outcomes. Patients undergoing angioplasty with stenting had a 30% risk reduction. Clopidogrel should be administered from 1 to 9 months. Patients undergoing stenting should receive the medication for at least 3-6 months32.

Previous studies with iGpIIb/IIIa confirmed a substantial reduction on adverse outcomes in high-risk patients with UA/NSTEMI (elevated troponin levels, persistent ischemia, and TIMI risk score > 4). The greatest benefit occurred in patients undergoing angioplasty (risk reduction of AMI or death around 40%). The CAPTURE trial evaluated the efficacy of abciximab in patients with unstable angina. Abciximab was associated with a reduction in 30-day mortality rate, myocardial infarction or urgent revascularization from 15.9% to 11.3%33. The PRISM34 and PRISM-PLUS35 trials demonstrated a reduction by 43% in the risk of adverse events after UA/NSTEMI (death or non-fatal AMI) within 7 days.

 

ANTICOAGULATION IN NSTEMI: UFH AND LMWH

A meta-analysis has demonstrated that UFH combined with ASA reduced the risk of death or myocardial infarction by 56% (p = 0.03) after NSTEMI. Medication should be continued for 2 to 5 days or until angioplasty/revascularization36.

LMWH has increased bioavailability and longer half-life than UFH. Dalteparin and nadroparin were similar to UFH. Enoxaparin was superior to UFH in the ESSENCE37 and TIMI 11B38 trials, and is the most used LMWH in UA/NSTEMI. Enoxaparin should be administered in two daily subcutaneous doses of 1 mg/kg for 2-5 days, or until angioplasty.

 

CHOICE OF HEPARIN FOR COMBINATION WITH GP IIB/IIIA INHIBITOR

At the present time, multiple therapies are used for the treatment of UA/NSTEMI patients. Safety and efficacy of LMWH or UFH combined with iGpIIb/IIIa was recently corroborated. The SYNERGY trial has demonstrated that both UFH and enoxaparin reduced adverse endpoints (death / AMI / myocardial ischemia). Similarly both agents, when combined with GpIIb/IIIa inhibitor and ASA and/or clopidogrel. There were no differences in terms of bleeding39.

 

EARLY INVASIVE VERSUS CONSERVATIVE STRATEGY

Early invasive strategy consists in performance of cardiac catheterization in the first 24 to 48 hours of presentation. The benefit of this strategy was observed in intermediate-risk and high-risk patients (TIMI > 4 risk score or high-risk in the AHA/ACC classification), with reduction in the adverse endpoints, when compared to conservative strategy. The TACTICS-TIMI 18 study demonstrated that death, non-fatal AMI or re-hospitalization for ACS was reduced from 19.4% to 15.9%40.

Conservative strategy demands an initial noninvasive evaluation, composed by an echocardiogram for assessment of left ventricular function followed by a cardiac stress test for detection of myocardial ischemia4.

Intermediate-risk patients may undergo ischemia testing after 48 to 72 hours of stable medical therapy. Cardiac catheterization is strongly recommended for patients with evidence of recurrent ischemia or positive non-invasive test, despite medical treatment4.

Current guidelines encourage an early invasive strategy in patients with recurrent ischemia, elevated levels of troponin, ST-segment depression, signs of heart failure or mitral regurgitation, ventricular dysfunction (EF < 40%), hemodynamic instability, sustained ventricular tachycardia, and angioplasty within the preceding 6 months or a history of myocardial revascularization4.

 

CONCLUSION

The understanding of pathophysiology of ACS and their treatment have evolved substantially over the last decades. Efforts to improve survival in STEMI have focused on reperfusion strategies. Early diagnosis and risk stratification have been considered the cornerstone of management for patients with UA / NSTEMI.

 

REFERENCES

01. Fox KA - Management of acute coronary syndromes: an update. Heart, 2004;90:698-706.

02. Tunstall-Pedoe H, Kuulasmaa K, Mahonen M, et al. Contribution of trends in survival and coronary-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA project populations. Monitoring trends and determinants in cardiovascular disease. Lancet, 1999;353:(9164):1547-1557.

03. Van de Werf F, Ardissino D, Betriu A, et al. Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J, 2003;24:28-66.

04. Anderson JL, Adams CD, Antman EM, et. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation, 2007;116:e148-e304.

05. Alpert JS, Thygesen K, Antman E, et al. Myocardial infarction redefined-a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol, 2000;36:959-969.

06. Menon V, Harrington RA, Hochman JS, et al. Thrombolysis and adjunctive therapy in acute myocardial infarction: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest, 2004;126:(Suppl3):549S-575S.

07. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Fibrinolytic Therapy Trialists' (FTT) Collaborative Group. Lancet, 1994;343:(8893):311-322.

08. 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.

09. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol, 2004;44:E1-E211.

10. Boersma E, Maas AC, Deckers JW, et al. Early thrombolytic treatment in acute myocardial infarction: reappraisal of the golden hour. Lancet, 1996;348:(9030):771-775.

11. Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI). Lancet, 1986;1:(8478):397-402.

12. An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction. The GUSTO investigators. N Engl J Med, 1993;329:673-682.

13. Van De Werf F, Adgey J, Ardissino D, et al. Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Lancet, 1999;354:(9180):716-722.

14. Morrison LJ, Verbeek PR, McDonald AC, et al. Mortality and prehospital thrombolysis for acute myocardial infarction: A meta-analysis. JAMA, 2000;283:2686-2692.

15. Bonnefoy E, Steg PG, Chabaud S, et al. Is primary angioplasty more effective than prehospital fibrinolysis in diabetics with acute myocardial infarction? Data from the CAPTIM randomized clinical trial. Eur Heart J, 2005;26:1712-1718.

16. Singh KP, Roe MT - ASSENT-4 PCI: should facilitated percutaneous coronary intervention be used in clinical practice? Nat Clin Pract Cardiovasc Med, 2006;3:420-421.

17. Silber S, Albertsson P, Aviles FF, et al. Guidelines for percutaneous coronary interventions. Eur Heart J, 2005;26:804-847.

18. Eisenberg PR - Role of heparin in coronary thrombolysis. Chest, 1992;101:(Suppl4):131S-139S.

19. Gurbel PA, Serebruany VL, Shustov AR, et al. Effects of reteplase and alteplase on platelet aggregation and major receptor expression during the first 24 hours of acute myocardial infarction treatment. GUSTO-III Investigators. Global Use of Strategies to Open Occluded Coronary Arteries. J Am Coll Cardiol, 1998;31:1466-1473.

20. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Lancet, 1988;2:(8607):349-360.

21. Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med, 2005;352:1179-1189.

22. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med, 2007;356:998-1008.

23. Montalescot G, Barragan P, Wittenberg O, et al. Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med, 2001;344:1895-1903.

24. Freemantle N, Cleland J, Young P, et al. beta Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ, 1999;318:(7200):1730-1737.

25. Pfeffer MA, McMurray JJ, Velazquez EJ, et al. Valsartan, captopril, or both in myocardial infarction complicated by heart failure, left ventricular dysfunction, or both. N Engl J Med, 2003;349:1893-1906.

26. Pitt B - Aldosterone blockade in patients with systolic left ventricular dysfunction. Circulation, 2003;108:1790-1794.

27. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med, 2004;350:1495-1504.

28. Granger CB, Goldberg RJ, Dabbous O, et al. Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med, 2003;163:2345-2353.

29. 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, 1998;339:436-443.

30. Antman EM, Cohen M, Bernink PJ, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA, 2000;284:835-842.

31. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol, 2002;40:1366-1374.

32. Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet, 2001;358:(9281):527-533.

33. Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study. Lancet, 1997;349:(9063):1429-1435.

34. A comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina. Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study Investigators. N Engl J Med, 1998;338:1498-1505.

35. 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, 1998;338:1488-1497.

36. Cohen M, Adams PC, Parry G, et al. Combination antithrombotic therapy in unstable rest angina and non-Q-wave infarction in nonprior aspirin users. Primary end points analysis from the ATACS trial. Circulation, 1994;89:81-88.

37. Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med, 1997;337:447-452.

38. Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial. Circulation, 1999;100:1593-1601.

39. Ferguson JJ, Califf RM, Antman EM, et al. Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial. JAMA, 2004;292:45-54.

40. Cannon CP, Weintraub WS, Demopoulos LA, et al. 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, 2001;344:1879-1887.

 

 

Received from Intensive Care Unit of Hospital Israelita Albert Einstein, São Paulo (SP), Brazil.

 

 

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