As an acute coronary syndrome is a thrombotic process all patients are immediately treated with anti-platelet agents.
Patients are monitored in a high-dependency environment and given adequate analgesia and oxygen.
In the setting of complete vessel occlusion (ST-elevation) urgent restoration of flow is achieved with thrombolytics or angioplasty.
If complete vessel occlusion has not occurred therapy is directed to reduce ischaemia and the development of further thrombus.
The initial management of a patient with an acute coronary syndrome involves general measures, including the use of analgesia and oxygen, and then specific treatments to reduce the short-term and long-term effects of the condition. Although there are similarities, the care pathway divides into two dependent on whether acute total vessel closure is suspected.
Detailed guidelines on the management of acute coronary syndromes have been produced by both the American Cardiac Societies (Krumholz et al. 2006) and the European Cardiac Society (Bassand et al. 2007).
This chapter will describe the generic management pathway and then the important steps in the initial further care in both cases of ST-segment elevation and non-ST–segment elevation.
5.2 First steps
The management of patients with a suspected acute coronary syndrome should occur within a high-dependency area and be directed to prompt and effective triage and initial treatment as time is critical to avoid an adverse outcome.
Patients should be monitored haemodynamically and by continuous electrocardiogram to detect rapidly any deterioration in their clinical condition. Secure intravenous access should be sought and the patient supplied with high-flow oxygen, via a facemask, to maintain arterial saturations above 90 per cent.
Pain is very detrimental to the myocardium during acute ischaemia as it leads to increased oxygen demand by the development of a tachycardia and hypertension. This then causes further ischaemia and potentially increases the degree of cardiac injury and the risk of malignant arrhythmias. Therefore adequate analgesia needs to be administered urgently. While obtaining other routes of delivery, sublingual glyceryl trinitrate (GTN) (2 puffs, 400 mcg) should be given and repeated if required. Unless this relieves all pain this should be supplemented with intravenous opiates (5–10 mg morphine sulphate with an appropriate anti-emetic). Maintenance of adequate arterial oxygen saturations with supplemental oxygen is also important for analgesia in the acute setting.
5.2.2 Anti-platelet agents
As the pathophysiology of acute coronary syndromes involves the development of platelet-rich thrombus within the coronary vessels it is critical to inhibit this process. Multiple pathways in platelet aggregation can be blocked, up to and including the ‘final common pathway’ of glycoprotein IIb/IIIa receptor binding. In all cases management should include agents to block the cyclo-oxygenase system (aspirin) and the ADP-receptor–dependent pathway (clopidogrel or ticlopidine). The only exception to this is individuals with active and uncontrollable bleeding, for instance intra-cerebrally, or known hypersensitivity. In the acute setting aspirin has an additive effect over thrombolysis and should be initiated at 300 mg (ISIS Group 1988). A loading dose of clopidogrel has also been shown to reduce the composite endpoint of death, myocardial infarction, and stroke from 11.47 per cent to 9.28 per cent (P < 0.005) (Fox et al. 2004, Sabatine et al. 2005) and at present the licensed regimen is 300 mg (followed by 75 mg daily). Ex vivo studies have suggested a more rapid time of onset when higher doses are employed and many units have increased this loading dose to 600 mg.
The initial therapeutic strategy is demonstrated in Figure 5.1.
In addition to these general measures specific strategies need to be applied in patients presenting with complications of their acute coronary syndrome (see Chapter 7).
At the end of Figure 5.1 the treatment options can be seen to diverge dependent on whether there is likely to be a completely occluded epicardial vessel (ST-segment elevation) or partially occluded vessel (non-ST–segment elevation). The next sections describe these pathways.
Where complete occlusion of the coronary artery has occurred rapid resolution of normal blood flow is required in order to prevent irreversible cell injury. This scenario is diagnosed from the presence of typical chest pain lasting over 20 minutes with significant ST-elevation or new left bundle branch block on the electrocardiogram. Reperfusion can be achieved in three different ways: pharmacologically, by percutaneous coronary intervention or by cardiac surgery. Not all options are available in every setting and the choice of strategy will largely depend upon this.
As the vessel is occluded with thrombus agents that act to break down this material are a logical therapeutic approach. A number of different agents have been studied and developed to lyse clots within arteries during a myocardial infarction and the major agents are summarized in Table 5.1.
Table 5.1 Major trials of thrombolytic agents
Trial and reference
GISSI Lancet 1986; 1: 397–401
11,712 patients with ST-elevation of less than 12 hours duration
21-day mortality reduced from 13% to 10.7% (P = 0.0002)
ISIS-2 ISIS-2 Group 1988
17,187 patients with suspected MI in last 24 hours
Five-week mortality improved 12% to 9.2% (P <0.05) and better if combined with aspirin
Tissue plasminogen activator
ASSET Lancet 1988 II: 525–30
5009 patients with acute myocardial infarction
One-month mortality reduced from 9.8% to 7.2% (P <0.05)
GISSI-2 Lancet 1990; 336; 65–71
12,381 patients comparing t-PA to streptokinase
No significant difference between the two agents
TIMI-1 Chesebro et al. 1987
290 patients comparing streptokinase, t-PA, and placebo
No difference in mortality but earlier normalization of flow with t-PA
ASSENT-2 Lancet 1999; 354; 716–722
16,949 patients comparing alteplase with tenecteplase
Tenecteplase was as safe and effective as alteplase and easier to administer
Hospitals vary on whether they give streptokinase (1.5 mU in 100 mL normal saline infused over 60 minutes) to most patients, reserving tPA or tenecteplase (0.5 mg/kg, 50 mg max) as IV bolus over 10 seconds followed by dalteparin (3000 U IV bolus) for young patients (less than 65 years) with anterior infarcts, or give the latter agent to all comers.
Speed of administration is critical. The most benefit is achieved with administration of a thrombolytic within 3 hours of the onset of pain (Widimsky et al. 2003). In some regions thrombolysis is given within the ambulance in order to accelerate the process (Weaver et al. 1990). As speed is important, this is measured and audited as the door-to-needle (or pain-to-needle) time and should ideally be less than 30 minutes. The objective of reperfusion is to achieve normal flow within the epicardial vessel, which from the Thrombolysis in Myocardial Infarction (TIMI) trials has been designated TIMI 3 flow (see definitions in Table 5.2). This, or TIMI 2 flow, is achieved in 62 per cent of patients treated with tissue plasminogen activator and 31 per cent with streptokinase at 90 minutes after administration (Chesebro et al. 1987). Efficacy can also be monitored by the effects of the agents on ST-segment elevation, which is partially correlated with restoration of flow to the epicardial vessel.
Table 5.2 TIMI grading
Partial filling of epicardial vessel
Complete, though slow filling
Normal flow within epicardial vessel
Any agent that acts by breaking down clots runs the risk of causing inadvertent bleeding in other territories (Table 5.3). For this reason caution has to be applied in certain settings to balance the risks of the thrombolytic causing unwanted bleeding and the benefits of restoring flow. Debate exists as to which of these contra-indications are absolute or relative and in each individual patient the risk of allowing the infarct to continue has to be balanced against the hazard. If thrombolysis is not possible urgent transfer to a centre able to perform percutaneous coronary intervention needs to be considered, though even in this case the risks of bleeding are still increased.
Table 5.3 Contraindications to thrombolysis
Thrombolytics should be administered with careful cardiac and haemodynamic monitoring as they can lead to reperfusion arrhythmias (atrial and ventricular), hypotension, and allergic reactions (in the case of streptokinase). Profound hypotension or allergy will require slowing or stopping of the agent, though it should be continued with arrhythmias and these managed as detailed in later chapters.
5.3.2 Percutaneous coronary intervention
In an appropriately staffed and equipped unit the restoration of normal blood flow (TIMI 3) in the epicardial vessel can be achieved more effectively with percutaneous coronary intervention (PCI). After visualizing the coronary anatomy the occluded or target vessel is crossed with a fine guidewire and a balloon is inflated to restore flow. Usually the procedure will also require the insertion of a coronary stent to optimize the final result. The speed of restoration of flow is paramount and is measured as the door-to-balloon time.
Multiple studies have compared the efficacy of thrombolytics to percutaneous coronary intervention, culminating in a meta-analysis showing the superiority of primary PCI (Keeley et al. 2003). Outcome is strongly dependent on the quality of the team and speed of action of the unit involved and favours the development of high-volume specialist centres. Various studies have looked at off-setting the advantages of PCI as a primary strategy against the delay in reperfusion that transferring patients entails (Widimsky et al. 2003). In a well-organized system where delays are kept to less than three hours this option offers a better long-term outcome (Anderson et al. 2003).
Table 5.4 Comparison of primary angioplasty with fibrinolysis for acute myocardial infarction
From Keeley et al. 2003
In addition to the mechanical opening of the vessel, studies have shown that aggressive platelet inhibition with glycoprotein IIb/IIIa inhibitors reduces the composite of death, myocardial infarction, and urgent revascularization at 30 days (6 per cent vs 14.6 per cent, P = 0.01) and six months (Montalescot et al. 2001). Local protocols vary, though the most common regimen is the initiation of abciximab (0.25 mg/kg bolus and 0.125 mcg/kg/min infusion for 12 hours) at the time of presentation prior to intervention. This treatment, particularly as it is combined with heparin, leads to an increased bleeding risk and the contra-indications listed for thrombolysis generally apply.
In the setting of a large thrombus burden within the blood vessel some operators favour the use of thrombus extraction devices or mechanisms to avoid distal embolization. Unfortunately there are no large trials to support these options and the details of their advantages and disadvantages are beyond the scope of this text.
In hypotensive patients, particularly in the context of cardiogenic shock, intervention and long-term outcome can be improved by the use of an intra-aortic balloon pump (Sanborn et al. 2000). This is inserted in the catheter laboratory via the femoral artery in individuals without significant peripheral vascular disease. It improves coronary perfusion and reduces cardiac afterload, though it requires continued heparinization and has increased vascular complications.
Due to the practical difficulties in organizing 24-hour primary PCI services a large number of studies have looked at the role of facilitated PCI (where agents are given prior to a definite PCI) and rescue PCI (where PCI is used when thrombolysis has failed). With the exception of abciximab immediately prior to intervention, no trial studying facilitated strategies has been shown to be beneficial, largely due to increased bleeding complications, and this cannot be recommended. Rescue PCI is beneficial when pain and ST-elevation persist 90 minutes after thrombolysis (composite of death, myocardial infarction, stroke, and heart failure reduced from 31 per cent to 15 per cent compared to conservative therapy, P < 0.01), though the results are less favourable to primary PCI (Gershlick et al. 2005).
5.3.3 Coronary artery bypass grafting
Although coronary artery bypass surgery is an effective treatment to restore coronary flow, it is rarely used due to the high operative mortality in patients undergoing operations immediately or within the first seven days of an infarct. It may have a role in cardiogenic shock, though with the increase in the options available percutaneously this is very rarely chosen.
5.4 Management of non-ST–segment elevation acute coronary syndromes
The treatment of non-ST elevation acute coronary syndromes involves the commencement of therapy to further reduce platelet aggregation, prevent ischaemia, and risk-stratify the patient. This section describes the commonly used strategies. The use of other agents to improve longer-term prognosis, such as statins and angiotensin-converting enzyme inhibitors, are covered in later chapters.
In addition to the oral anti-platelets aspirin and clopidogrel, the coagulation pathways should be inhibited with heparin. Due to improved bioavailability, subcutaneous low molecular weight heparins are preferred over unfractionated preparations (Antman et al. 1999). Table 5.5 details the evidence and dosing regimens for these heparins.
Table 5.5 Low molecular weight heparins
Trial and reference
ESSENCE N Engl J Med 1997, 337; 447–452
Death/infarct/angina reduced at 14 days (16.6% vs 19.8% placebo, P = 0.019)
1 mg/kg twice daily for 2–8 days
TIMI-11B Antman et al. 1999
Death/infarct/revascularization reduced at 8 days compared to unfractionated heparin (12.4% vs 14.5%, P = 0.048)
1 mg/kg twice daily
FRISC Lancet 1996, 347; 561–568
6-day mortality reduced from 4.8% (placebo) to 1.8%
120 U/kg twice daily for 6 days
Heparin should be continued for 48–72 hours or until after coronary angiography and definitive therapy. At the time of coronary intervention some operators continue to use these heparins, though most supplement them with unfractionated preparations. In patients with renal failure (glomerular filtration rate <30 mL/min) unfractionated heparin should be used.
In high-risk individuals with ongoing chest pain, dynamic electrocardiographic changes, and a raised troponin level, further platelet inhibition is required. The use of eptifibatide (small molecular glycoprotein IIb/IIIa inhibitor) has been shown to reduce the composite endpoint of death and non-fatal myocardial infarcts (7.6 per cent vs 9.1 per cent, P = 0.01; PURSUIT Trial Investigators 1998). Due to the increased haemorrhagic complications associated with these agents they should be reserved for high-risk individuals and used as a bridge to coronary angiography and intervention.
In order to reduce myocardial injury and relieve pain it is important to reduce the ischaemic burden. This is partially achieved by pain relief, though also markedly improved by the early initiation of beta-blockade. Due to the potential for cardiac destabilization this is usually commenced with a short-acting agent, such as metoprolol (12.5 to 25 mg). In patients with late presentations of full-thickness myocardial infarcts beta-blockers have been shown to improve survival, thought to be mostly by reducing the chance of cardiac rupture (ISIS Group 1986). After initiation the dose can be increased, and then a longer-acting agent substituted. Only in individuals with clear reversible airways disease, rather than fixed chronic obstruction, should rate-slowing calcium channel blockers be used, and even in these cases a cardioselective beta-blocker, such as bisoprolol (2.5–10 mg), can often be tolerated.
Although nitrates do not improve survival they can be very effective as analgesia, by opening vessels suffering from the spasm that often accompanies an unstable plaque. Although initially given sublingually they are then usually administered intravenously as an infusion at 1–10 mcg/min. Due to their mechanism of action their effectiveness diminishes with time and if pain is relieved they should be stopped in order to avoid tolerance.
Early invasive investigation and subsequent revascularization has been shown to be beneficial (six-month death/myocardial infarction reduced from 12.1 per cent to 9.4 per cent, P = 0.03; FRISC II 1999). This ideally should occur within 48 hours, though in many cases this is not practical. Ongoing pain or high-risk features, such as hypotension or dynamic electrocardiographic changes, would favour immediate transfer to a unit able to perform these procedures. The subsequent management of patients who are not urgently transferred for coronary angiography is considered in later chapters.
Anderson HR, Nielsen TT, Rasmussen K, et al. (2003) A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. New Engl J Med 349(8): 733–742.Find this resource:
Antman EM, McCabe CH, Gurfinkel EP, et al. (1999) Thrombolysis in Myocardial Infarction-11B. Circulation 100: 1593–1601.Find this resource:
Bassand J-P, Hamm CW, Ardissino D, et al. (2007) Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J 28: 1598–1660.Find this resource:
Chesebro JH, Knatterud G, Roberts R, et al. (1987) Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 76(1):142–54.Find this resource:
Cohen M, Demers C, Gurfinkel EP, et al. (1997) A Comparison of Low-Molecular-Weight Heparin with Unfractionated Heparin for Unstable Coronary Artery Disease. The Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-Wave Coronary Events Study Group, New Engl J Med 337: 447–52.Find this resource:
Fox KA, Peters RJG, Mehta SR, et al. (2004) Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularization for non-ST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial. Circulation 108(14): 1682–1687.Find this resource:
FRISC. (1996) Low-molecular-weight heparin during instability in coronary artery disease, Fragmin during Instability in Coronary Artery Disease (FRISC) study group. Lancet 347(9001): 561–8.Find this resource:
FRISC II. (1999) Fragmin and fast revascularisation during instability in coronary artery disease II. Lancet 354: 701–707.Find this resource:
Gershlick, Stephens-Lloyd A, Hughes S, et al. (2005) Rescue angioplasty after failed thrombolytic therapy for acute myocardial infarction. New Engl J Med 353: 2758–2768.Find this resource:
GISSI. (1986) Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico (GISSI). Lancet 1: 397–401.Find this resource:
GISSI-2. (1990) A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. Lancet 336: 65–71.Find this resource:
ISIS Group. (1986) Randomized trial of intravenous atenolol among 16027 case of suspected acute myocardial infarction. Lancet 304: 57–66.Find this resource:
ISIS Group. (1988) Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17187 cases of suspected acute myocardial infarction. Lancet 2: 349–360.Find this resource:
Keeley EC, Boura JA, Grines CL, et al. (2003) Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 361: 13–20.Find this resource:
Krumholz HN, Jeffrey L, Anderson JL, et al. (2006) ACC/AHA clinical performance measures for adults with ST-elevation and non-ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. Circulation 113(5): 732–761.Find this resource:
Montalescot G, Barragan P, Wittenberg O, et al. (2001) Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. New Engl J Med 344(25): 1895–1903.Find this resource:
PURSUIT Trial Investigators. (1998) Inhibition of the platelet glycoprotein IIb/IIIa receptor with eptifibatide in patients with acute coronary syndromes. New Engl J Med 339: 436–443.Find this resource:
Sabatine MS, Cannon CP, Gibson CM, 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. J Am Med Assoc 294(10): 1224–1232.Find this resource:
Sanborn TA, Sleeper LA, Bates ER, et al. (2000) Impact of thrombolysis, intra-aortic balloon pump counterpulsation, and their combination in cardiogenic shock complicating acute myocardial infarction: a report from the SHOCK Trial Registry. J Am Coll Cardiol 36: 1123–1129.Find this resource:
Van De Werf F, Adgey J, Ardissino D, et al. (1999) Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial. Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2). Lancet 354: 716–22.Find this resource:
Widimsky P, Budesínský T, Vorác D, et al. (2003) Long distance transport for PCI versus immediate fibrinolysis in acute myocardial infarction (Prague-2). Eur Heart J 24: 94–104.Find this resource:
Wilcox RG, von der Lippe G, Olsson CG, et al. (1988) Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction. Anglo-Scandinavian Study of Early Thrombolysis. (ASSET). Lancet 2: 525–30.Find this resource: