If I had an acute coronary syndrome…
Authors: Joseph M Delehanty, Frederick S Ling, Bradford C Berk
Journal: The Lancet (1999)

… I would arrange for transport and go directly to the nearest hospital emergency department. If a tertiary-care hospital with specialists in cardiovascular disease were nearby I would ask to be taken there. However, time is of the essence in the management of acute coronary syndromes (ACS) and the most important initial assessment is the appropriate diagnosis. I hope that on arrival in the emergency department my chest pain would be recognised as cardiac in nature and that I would be triaged to a critical care pathway that results in immediate diagnosis. Unstable angina may be difficult to distingush from acute myocardial infarction and I would like to have an electrocardiogram (ECG) done as soon as possible. If the ECG showed ST segment elevation, then I would benefit from immediate reperfusion therapy. Administration of thrombolytic therapy or primary angioplasty would be appropriate depending on the physician's expertise and time required for therapy. In both instances the earlier that treatment is initiated the better my outlook would be. In the event that my initial ECG did not show ST segment elevation, I would hope to undergo rapid evaluation to determine the likelihood that my symptoms were due to cardiac ischaemia. In addition, I would like to know how serious my condition was; specifically what is the short-term risk of death or myocardial infarction.1Braunwald E Jones RH Mark DB et al.Diagnosing and managing unstable angina.in: Agency for Health Care Policy and Research. Circulation. 90. 1994: 613-622Google Scholar Risk stratification should be based on features of the clinical presentation, ECG findings, and laboratory tests. In the analysis of the GUSTO-1 study, the following clinical features predicted mortality at 30 days: age, systolic blood pressure, and heart rate. Specifically, age older than 70 years, heart rate more than 100 beats per min, and systolic blood pressure below 100 mm Hg provided information about 50% of the mortality risk.2GUSTO InvestigatorsAn International randomized trial comparing four thrombolytic strategies for acute myocardial infarction.N Engl J Med. 1993; 329: 673-682Crossref PubMed Scopus (3699) Google Scholar Other clinical features that predict high risk are presence of continuing rest pain at the time of evaluation, history of myocardial infarction or revascularisation procedure, new mitral valve insufficiency, and signs of impaired left-ventricular function such as an S3 or rales. The risk at 30 days is also strongly related to features of the ECG at the time of presentation with chest pain. The incidence of death or myocardial infarction is 10% with ST segment depression, 5% with T wave inversion, and only 1–2% if there are no changes. Thus, the presence of ST depression would place me in a high-risk category. Recent myocardial necrosis, as shown by raised creatine (CPK-MB), troponin I, or troponin C strongly increases risk. Raised troponin has been shown to be strongly related to mortality at 42 days after infarction.3Antman EM Tanasijevic MJ Thomson B et al.Cardiac-specific troponin I levels to predict the risk of mortality in patients with acute coronary syndromes.N Engl J Med. 1996; 335: 1342-1349Crossref PubMed Scopus (1551) Google Scholar Individuals at high risk of myocardial infarction or death should undergo an-early invasive intervention. Intermediate risk characteristics would include episodes of angina at rest that resolved, nocturnal angina, dynamic T wave changes and pathological Q waves on ECG, or age older than 65–70 years. Low-risk findings would be the presence of new onset exertional angina, increased frequency or intensity of angina, and a normal resting ECG. Early treatment can be classified according to three approaches: invasive intervention, stabilisation followed by invasive intervention, and medical intervention. In all three approaches, and coincident with initial evaluation, I would expect to receive aspirin at a dose of at least 80 mg. There is strong evidence that supports use of aspirin in all patients with suspected ACS to reduce incidence of myocardial infarction and death. The immediate use of nitrates and oxygen is less well supported by evidence from clinical trials, but is so commonly used with few side-effects that I would expect to receive both. Similarly, the use of β-blockers in unstable angina is not as well established as in acute myocardial infarction, but if I did not have any contraindications such as bradycardia, hypotension, pulmonary congestion, or bronchospasm, I would want to receive an oral β-blocker at the time of evaluation. If the initial evaluation determined that I was in a low-risk category, I would want to receive medical intervention. This intervention would be treatment with aspirin and probably β-blockers as well as nitrates on an as-needed basis. I would not necessarily need to be admitted to hospital as long as I was followed closely as an outpatient. I would want to undergo non-invasive risk stratification if I had no recurrence of symptoms, and if it confirmed a low risk, then I would continue medical therapy and secondary prevention as described below. If my initial evaluation found that I was at intermediate risk, I would want to be treated with subcutaneous low-molecular-weight heparin (enoxaparin, 1 mg/kg twice daily). This regimen has been compared with intravenous heparin and has been found to be superior in terms of reducing risk of death, myocardial infarction, or recurrent angina in the 2–4 weeks after presentation.4Cohen M Demers C Gurfinkel EP et al.A comparison of low-molecular-weight heparin with unfractrionated heparin for unstable coronary artery disease.in: Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 337. 1997: 447-452Google Scholar Data from the CAPTURE trial also support the concept that waiting 24 h before invasive intervention while being treated with a platelet glycoprotein IIb/IIIa inhibitor (abciximab) is safe.5CAPTURE I Randomised placebo-controlled trial of abciximab before and during coronary intervention in refractory unstable angina: the CAPTURE Study.Lancet. 1997; 349: 1429-1435Summary Full Text Full Text PDF PubMed Scopus (1425) Google Scholar Other glycoprotein IIb/IIIa inhibitors have been tested including tirofiban in PRISM6PRISM Study InvestigatorsA comparison of aspirin plus tirofiban with aspirin plus heparin for unstable angina.in: Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) Study. N Engl J Med. 338. 1998: 1498-1505Google Scholar and eptifibatide in PURSUIT.7PURSUIT Trial InvestigatorsInhibition of platelet glycoprotein IIb/IIIa with eptibatide in patients with coroanry syndromes.in: Platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrillin therapy. N Engl J Med. 339. 1998: 436-443Google Scholar Both trials also showed significant decreases in the composite endpoint of death and non-fatal myocardial infarction at 48 h. However, I favour enoxaparin because of safety and cost advantages. In the future, oral glycoprotein IIb/IIIa inhibitors may be used in this situation. If I did not have any recurrent symptoms after 48 h (successful stabilisation), I would want to have several management options available. I could undergo non-invasive risk stratification by exercise echocardiography or stress nuclear scintigraphy. If the stress test showed minimal ischaemic myocardium, I could be maintained on medical treatment, whereas if significant ischaemia were discovered, I would proceed to coronary angiography with subsequent revascularisation being decided by the results. Alternatively, I could decide to proceed immediately to elective coronary angiography. On the basis of the available evidence, there is no overwhelming benefit of one approach over the other. If I were at a hospital where no angiography facilities were available, I would be comfortable staying there and undergoing non-invasive risk stratification. If I am classified as a high-risk patient this situation would be a challenging one, because the treatment of such patients has been undergoing rapid change and the best therapeutic approach is not established. If I were a high-risk patient, I would want therapy started with intravenous heparin and an intravenous infusion of a platelet glycoprotein IIb/IIIa receptor inhibitor, such as tirofiban or eptifibatide. These agents have been shown to significantly reduce the risk of myocardial infarction, refractory ischaemia, and death in the acute setting with a protection that extends up to 6 months after presentation.7PURSUIT Trial InvestigatorsInhibition of platelet glycoprotein IIb/IIIa with eptibatide in patients with coroanry syndromes.in: Platelet glycoprotein IIb/IIIa in unstable angina: receptor suppression using integrillin therapy. N Engl J Med. 339. 1998: 436-443Google Scholar, 8PRISM-PLUS InvestigatorsInhibition of the platelet glycoprotein IIb/IIIa receptor with tirofiban in unstable angina and non-Q-wave myocardial infarction.in: Platelet Receptor Inhibitor in Ischemic Syndrome Mangement in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS). N Engl J Med. 338. 1998: 1488-1497Google Scholar The greatest benefit from the use of these agents is observed in patients who undergo revascularisation. If I were at a hospital that did not offer the option of coronary intervention, I would want to be transferred to such a hospital as soon as my condition was judged to be sufficiently stable to allow transport. In fact, if I were admitted to a hospital that had an advanced cardiac catheterisation facility and skilled coronary interventionalists I would prefer to have coronary angiography done immediately. Cardiac catheterisation in the setting of unstable angina is safe and provides a direct assessment of ischaemia and left-ventricullar function including assessment of regional wall motion. Coronary angiography allows expedited triage of patients with minimal coronary artery disease who can continue medical therapy. Alternatively, angiography rapidly indicates which patients need bypass surgery or can benefit from immediate therapy such as percutaneous coronary intervention. If coronary angiography revealed a high-grade stenosis that accounted for my acute coronary syndrome, I would hope for a revascularisation strategy that would include platelet glycoprotein IIb/IIIa inhibitors and immediate coronary intervention. I believe that the paradigm for management of unstable angina has shifted to an early invasive approach that should include the complementary use of platelet glycoprotein IIb/IIIa inhibitors (eg, abciximab, tirofiban, or eptifibatide) and coronary intervention with intracoronary stents. In the past, patients with unstable angina who underwent coronary intervention soon after presentation were at increased risk of adverse cardiac events. The advent of intracoronary stents improved the overall procedural success of coronary intervention, but did not affect the risk of adverse cardiac events in unstable angina, even with modern antiplatelet regimens, such as aspirin and ticlopidine. More intensive anticoagulation with platelet glycoprotein IIb/IIIa inhibitors has overcome the historical barrier of adverse events after acute intervention in unstable angina. Stents, which are used in 60–80% of all coronary interventions, allow a rapid and predictable means of restoring normal laminar antegrade flow. The recent availability of glycoprotein IIb/IIIa inhibitors represents a substantial medical advance because these agents provide improved antithrombotic coverage and can prevent periprocedural myocardial infarction and subacute thrombosis, the Achilles heel of stenting. In the EPISTENT trial, 2399 patients who were assigned abciximab and stenting had a greater than 50% decrease in the composite endpoint of death, myocardial infarction, or urgent revascularisation at 30 days, compared with patients assigned stenting followed by aspirin and ticlopidine (without abciximab)9The EPISTENT InvestigatorsRandomised placebo-controlled and balloon-angioplasty-controlled trial to assess safety of coronary stenting with use or platelet glycoprotein-IIb/IIIa blockade.Lancet. 1998; 352: 87-92Crossref PubMed Google Scholar With dose reductions in heparin and careful anticoagulation monitoring, the combination of glycoprotein IIb/IIIa inhibitors and heparin maintains effective anticoagnlation without an increase in major bleeding events. Importantly, the early invasive intervention approach decreases the length of hospital stay (to fewer than 2 days on average in our hospital). Future trials to confirm my belief in a strategy that emphasises glycoprotein IIb/IIIa inhibition, early invasive therapy, or both in unstable angina include Treat Angina with Aggrastat and Determine Cost of Therapy with Invasive or Conservative Strategies (TACTICS-TIMI 18) trial10Cannon CP Weintraub WS Demopoulos LA Robertson DH Gormley GJ Braunwald E Invasive versus conservative strategies in unstable angina and non-Q-wave myocardial infarction following treatment with tirofiban: rationale and study design of the international TACTICS-TIMI 18 Trial.in: Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy. Thrombolysis In Myocardial Infarction. Am J Cardiol. 82. 1998: 731-736Google Scholar and the Global Use of Strategies to Open Coronary Arteries (GUSTO-IV) trial for acute coronary syndromes. When I leave the hospital, I want to make sure that I do not return for many years. An important therapy is to lower my lipids to concentrations that are found in strict vegetarians. If tests indicated that my LDL was above 3·25 mmol/L (100 mg/dL), I would begin therapy with an HMG-CoA reductase inhibitor with a target of reducing my LDL to below 2·6 mmol/L. Although the early use of such agents is not yet proven, I believe that the potential benefits outweigh the potential risks. The use of antioxidant vitamins is also controversial. Beneficial effects in patients with coronary artery disease have been observed for vitamin E in the CHAOS study, in which non-fatal myocardial infarction was decreased,11Stephens NG Parsons A Schofield PM Kelly F Cheeseman K Mitchinson MJ Randomised controlled trial of vitamin E patients with coronary disease: Cambridge Heart Antioxidant Study.Lancet. 1996; 347 (CHAOS): 781-786Summary PubMed Scopus (1669) Google Scholar and for the antioxidant drug probucol in the MVP study, in which restenosis after balloon angioplasty was reduced.12Tardif JC Coté G Lespérance J et al.Probucol and multivitamins in the prevention of restenosis after coronary angioplasty.N Engl J Med. 1997; 337 (Multivitamins and Probucol Study Group): 365-372Crossref PubMed Scopus (536) Google Scholar However, a many studies have failed to show significant benefit of antioxidants. If I had an ACS I would want to be assessed as quickly as possible at the nearest medical facility. If I were deemed to be at high risk of myocardial infarction or death, then I would want to receive aggressive antiplatelet therapy and be transferred to a facility where invasive coronary intervention was available. If my risk was not judged to be high, I would want to receive treatment at the initial hospital with subsequent non-invasive risk assessment and therapy that was guided by the results of that evaluation. Importantly, I would want to be cared for by a specialist trained in this common disease that now has new and powerful therapeutic possibilities.