Percutaneous Coronary Intervention for Non ST-Elevation Acute Coronary Syndromes: Which, When and How?

Percutaneous Coronary Intervention for Non ST-Elevation Acute Coronary Syndromes: Which, When and How? Robert K. Riezebos, MDa,*, Jan G.P. Tijssen, PhDb, Freek W.A. Verheugt, MD, PhDa, and Gerrit J. Laarman, MD, PhDc The presentation of patients with suspected non ST-elevation acute coronary syndromes is quite diverse. Therefore, the diagnostic workup and choice of treatment may vary accordingly. Major issues regarding the evaluation are the likelihood of the diagnosis and the risk for adverse events. These factors should guide the choice of diagnostic test. Patients with increased risk for ischemic events and patients with recurrent ischemia are most likely to benefit from revascularization. In addition, when percutaneous coronary intervention is considered, evidence suggests that sufficient time should be allowed for pharmacologic stabilization, reducing the possibility of periprocedurally inflicted myocardial infarction. However, postponement of intervention may lead to an increase of new spontaneous events, and high-risk patients should apply for revascularization soon after pharmacologic stabilization. The extent of revascularization performed by percutaneous coronary intervention depends predominantly on patient characteristics and anatomy but should be limited to flow-obstructive lesions. In conclusion, patients presenting with non–ST elevation acute coronary syndromes constitute a very diverse population; diagnostic workup, treatment, and the timing of a possible intervention should be tailored individually. © 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:509 –515) Patients with chest pain represent a large and increasing proportion of all acute medical presentations worldwide. Of all those presenting for evaluation, only a minority have acute coronary syndromes (ACS). Distinguishing which patients have ACS remains a diagnostic challenge. The principal pathophysiologic mechanism of ACS is myocardial underperfusion, which is caused by atherosclerotic plaque rupture or erosion, with different degrees of superimposed thrombus.1,2 Electrocardiography provides the initial classification. Patients are divided into those with persistent ST-segment elevation and those without persistent ST-segment elevation or non ST-elevation ACS (NSTEACS). In this review, we discusses the diagnostic challenges when NSTEACS are suspected. In addition, we address the role of risk stratification in relation to the choice of treatment strategy. When an invasive approach is preferred, an important issue is the timing of the intervention. The available evidence on this topic is discussed in detail. We conclude with the evidence regarding the type and extent of revascularization in patients with multivessel disease. Diagnostics and Risk Assessment In patients presenting with suspected NSTEACS, 2 major issues must be addressed. The first challenge is to confirm the diagnosis. Guidelines recommend the use of elementary tools, such as symptoms, risk profile for coronary a Onze Lieve Vrouwe Gasthuis; bAcademic Medical Center, University of Amsterdam, Amsterdam; and cTweeSteden Ziekenhuis, Tilburg, The Netherlands. Manuscript received August 16, 2010; revised manuscript received and accepted October 5, 2010. *Corresponding author: Tel: 31-20-5993033; fax: 31-20-5994618. E-mail address: [email protected] (R.K. Riezebos).

0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.amjcard.2010.10.016

artery disease, electrocardiography, and biomarkers, to estimate the likelihood of disease. In addition, echocardiography in the acute phase can be used to clarify the diagnosis.1,3 However, the diagnosis sometimes remains uncertain. In these cases, the clinical probability of ACS should be assessed.4 Although American College of Cardiology (ACC) and American Heart Association (AHA) as well as European Society of Cardiology (ESC) guidelines do not provide guidance on this topic, the next diagnostic test of choice should depend on the likelihood of disease. In Figure 1, an algorithm is proposed in which the preferred performance of a diagnostic test is related to the estimated probability of NSTEACS. In case of low clinical probability, patients are to be discharged safely, so a diagnostic test should be used with high sensitivity and high negative predictive value. Ischemia testing such as exercise testing with or without an imaging modality is frequently used in the subacute setting. However, such tests are most useful in patients with intermediate probability of ACS. In our opinion, poorly performing tests, such as treadmill or bicycle exercise tests, should be restricted to prognostic purposes only. Despite being not recommended by current ESC guidelines, computed tomographic angiography (CTA) is at present the most accurate noninvasive test to rule out coronary artery disease.1,5 New sophisticated scan protocols, using prospective electrocardiographically gated triggering, substantially reduce radiation exposure (effective dose value approximately 3 mSv), without reducing image quality.6 Extracardiac findings such as pulmonary tumors, pulmonary embolism, and aortic dissection can also be detected.7 In selected patients with acute chest pain, the diagnostic accuracy of CTA is excellent.8 In addition, this approach is more cost effective and less time-consuming.9 www.ajconline.org

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Figure 1. Algorithm showing the clinical application of diagnostic tests according to the probability of NSTEACS. ECG ⫽ electrocardiography.

In case of a high probability of ACS, patients should be admitted to the hospital for clinical follow-up and treatment. In these patients, false-positive results are more likely to occur. Accordingly, the diagnosis of ACS should be waived only on the basis of tests with high sensitivity and specificity, invasive coronary angiography currently being the gold standard. In this population, coronary angiography is able to exclude coronary artery disease reliably. This should be strived for, because even in the presence of electrocardiographic changes and troponin increase, about a fifth of the patients suspected of high-risk NSTEACS show no significant lesions on coronary angiography.10,11 These patients generally are at low risk and should be evaluated for alternative pathologies. Because of the absence of validated scoring systems to estimate the probability of NSTEACS in patients with chest pain, there is limited information on the distribution of the eventual diagnoses across the various levels of suspicion of ACS. A small trial by Goldstein et al9 evaluated the use of CTA in about 200 patients with chest pain and low probability of ACS. The mean Thrombolysis In Myocardial Infarction (TIMI) risk score was 1.2. The number of patients diagnosed with NSTEACS was about 10%, and the remainder had noncardiac chest pain. The percentage of patients who underwent percutaneous coronary intervention (PCI) was 4%, and the percentage requiring coronary artery bypass grafting (CABG) was 2%.9 In the Optimal Timing of PCI in Unstable Angina (OPTIMA) trial, about 250 patients

with suspected intermediate- to high-risk NSTEACS underwent acute coronary angiography.11 The mean TIMI risk score was 3.8. Of these, 78% were diagnosed with NSTEACS, and the remainder had noncardiac chest pain. Of all patients, 55% were treated with PCI, and 10% underwent CABG. The second issue to be addressed in patients with suspected NSTEACS involves risk assessment. Patients with NSTEACS represent a prognostically heterogenous group. Therefore, risk stratification plays a central role in evaluation and management. For this purpose, multiple scoring models have been developed, with the Global Registry of Acute Coronary Events (GRACE) and TIMI risk scores being the most widely used. The 2 models show a strong relation between indicators of the likelihood of NSTEACS and prognosis.12,13 The GRACE risk tool was developed on the basis of data from a large multinational cohort study (GRACE) and validated in subsequent GRACE and Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb cohorts.12,14 Recently, the GRACE score was prospectively revalidated in a large contemporary cohort.15 The TIMI score was developed using data from the TIMI 11B trial13 and prospectively validated in several cohorts, including that of the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy (TACTICS)–TIMI 18 trial.16 The GRACE score estimates the risk for death up to 6 months, and the TIMI risk score addresses the 14-day risk for death, recurrent myocardial infarction (MI) or urgent revascularization. This risk estimation, together with individual patient characteristics, should further guide treatment strategy. Indications for Urgent Revascularization A subset of patients with NSTEACS are considered to have such an increased mortality risk that immediate revascularization is recommended.1,2 These include cardiogenic shock, severe left ventricular dysfunction, suspected left main stem disease, recurrent or refractory ischemia at rest despite intensive pharmacologic treatment, mechanical complications such as acute mitral regurgitation, and sustained ventricular tachycardia. This recommendation is based on a single study that suggested better outcomes with revascularization in patients presenting with cardiogenic shock.17 However, most patients can be medically stabilized. These patients should be evaluated for an invasive approach. Routine Invasive Versus Selective Invasive Therapy In the past 2 decades, multiple trials have evaluated different clinical strategies regarding coronary angiography and subsequent revascularization of clinically stabilized patients with NSTEACS. Two general approaches have emerged, the first being the “early invasive” or “routine invasive” strategy, involving routine early coronary angiography followed by revascularization when appropriate. The second is the “conservative” or “selective invasive” approach, with initial pharmacologic management and coronary angiography followed by revascularization for recurrent ischemia only. This new ischemia may either be

15/596 (2.5%) 15/604 (2.5%) 59/596 (10%)

36/915 (4%) 41/895 (4.5%) 44/915 (5%)

39/1,106 (3.5%) 76/1,106 (6.9%) 53/1,114† (4.8%)

37/114 (3.3%)

36/1,226 (2.9%) 23/1,207 (1.9%) 124/1,226 (10.1%) 94/1,207* (7.8%)

90/604‡ (15%) 40% 54% 61% ICTUS20

* p ⫽ 0.03; † p ⫽ 0.002; ‡ p ⫽ 0.005. FU ⫽ follow-up; RI ⫽ routine invasive; SI ⫽ selective invasive.

79% 24–48 hours

34/895 (4%) 16% 28% 57%

TACTICS– TIMI 1816 RITA 319

1997–2001 (1-year FU) 2001–2003 (1-year FU)

⬍72 hours

36%

29% 35% 42% 64% 4–48 hours

18% 37% 42% 77% ⬍7 days FRISC II

18

1996–1998 (6-month FU) 1997–1999 (6-month FU)

RI % PCI % Revascularization % Revascularization

% PCI

SI RI

Timing of Catheterization in the Routine Invasive Approach Time Frame Patient Inclusion Trial

Table 1 Methodologic differences among trials evaluating routine versus selective invasive approach in non ST-elevation acute coronary syndromes

MI

SI

Primary Trial Outcome

RI

Mortality

SI

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511

spontaneous or provoked by noninvasive stress testing.1,2 Currently, AHA and ACC as well as ESC guidelines support routine invasive management in intermediate- to highrisk patients with NSTEACS.1,2 Four large randomized controlled trials have dominated the debate on the routine performance of invasive diagnostics in NSTEACS. The results, unfortunately, were quite diverse (Table 1). In 1999, the Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease (FRISC) II trial showed a significant reduction in the combined end point of death and MI with the routine invasive approach.18 The observed difference was driven mainly by an excess in MI in the selective invasive group. The TACTICS– TIMI 18 trial, published in 2001, showed similar results: a decrease in MI but no significant mortality benefit.16 In 2003, the Randomized Intervention Trial of Unstable Angina (RITA) 3 trial failed to show any benefit for death or MI.19 Ultimately, in 2005, the Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) trial was published.20 This study, with optimal medical treatment in both arms, showed an increased MI risk in the routine invasive arm, with no difference in mortality. Interpretation of the study results is difficult because of important differences in method. Foremost, when the studies are compared, there appears to be a marked variation in the intensity of revascularization between study arms (Table 1). The conservative arm of the ICTUS trial20 showed a revascularization rate similar to the routine invasive arm in RITA 3.19 Also, the definition of MI differed between the trials. The low biomarker threshold used in the ICTUS trial20 may partly explain the higher number of MIs in patients requiring PCI. The improved use of anticoagulants, dual-antiplatelet therapy, statins, and angiotensin-converting enzyme inhibitors may also be part of the assumed demise of the routine invasive treatment benefit. This is most clear for the use of statins. In the FRISC II18 and TACTICS–TIMI 1816 trials, approximately 1/2 the patients received statins at discharge. In RITA 3,19 this had already increased to 70%, whereas the ICTUS trial20 provided high-dose statin treatment to 92% of patients. Although less sharp, the use angiotensin-converting enzyme inhibitors showed similar patterns. On the basis of the ICTUS trial, the current AHA and ACC guidelines acknowledge the option of a selective invasive strategy with aggressive medical treatment.2 It may not be surprising that long-term (5-year) follow-up of the aforementioned trials showed discordant results.21,22 Remarkably, the initial negative RITA 3 trial suggested a marked 5-year benefit in the routine invasive group regarding death and MI (odds ratio 0.78, 95% confidence interval 0.61 to 0.99, p ⫽ 0.04).23 Indeed, a recent meta-analysis based on individual 5-year follow-up patient data from FRISC II, RITA 3, and ICTUS showed a reduction in MI using the routine invasive strategy.24 The relation between treatment effect and patient risk has been evaluated in subanalyses of several trials. Regardless of the risk score used, there appeared to be a consistent treatment benefit for the invasive approach in high-risk patients compared to low-risk patients. The FRISC II and TACTICS–TIMI 18 trials as well as the 5-year follow-up of RITA 3 showed the greatest benefit of the routine invasive

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Delayed

21/207 (10.1%) 59/1,438 (4.1%) 26/69 (37.7%) 8/177 (4.5%)

Early

12/203 (5.9%) 57/1,593 (3.6%) 44/73* (60.3%) 16/175 (9.1%)

3/207 (1.4%) 46/1,593 (2.9%) 0/73 (0%) 5/175 (2.9%)

0/203 (0.2%) 47/1,438 (3.3%) 0/69 (0%) 2/177 (1.1%)

approach in high-risk patients.16,18,23 This resulted in a wide acceptance of the routine invasive approach in this subpopulation. The clinical application of the aforementioned TIMI and GRACE risk scores has been evaluated extensively. Remarkably, recent data from the GRACE registry suggest the presence of an inverse relation between patient risk and the rate of PCI.25 In daily practice, angiographic findings and referral practice may more substantially influence the decision to proceed to PCI than patients’ risk status. In conclusion, the different outcomes in the large trials evaluating the invasive approach in NSTEACS mainly reflect the changes in study protocols and in pharmacologic treatment. For clinical practice, it seems reasonable to consider a liberal selective invasive approach equivalent to a temperate routine invasive approach. The patients with the highest risks for adverse outcomes are thought to derive the greatest benefit from invasive evaluation and revascularization. However, because clinical judgment on risk estimation appears to be challenging, the use of systematic and accurate risk stratification methods seems important.

64% 60% 100% 80%

NA 16 2.5 NA

86 50 1.8 20.5

70% 55% 99% 70%

NA 52 27 NA

Timing of Percutaneous Coronary Intervention

* p ⫽ 0.005. NA ⫽ not available.

2.4 14 2 1.1 ISAR COOL TIMACS27 OPTIMA11 ABOARD28

26

2000–2002 2003–2008 2004–2007 2006–2008

Median Time to PCI (hours) % PCI Median Time to catheterization (hours) Median Time to PCI (hours) Median Time to Catheterization (hours)

% PCI

Delayed strategy Early strategy

Time Frame Patient Inclusion Trial

Table 2 Methodologic differences among trials evaluating the timing of invasive approach in non ST-elevation acute coronary syndromes

MI

Trial Outcome at 1 Month

Early

Mortality

Delayed

512

In the past few years, several studies have evaluated the influence of the timing of intervention in patients with NSTEACS. Once again, comparison of data and interpretation of the results are difficult, mainly because of methodologic differences among the studies (Table 2). Current AHA and ACC as well as ESC guidelines do not give specific recommendations on this topic.1,2 The first study published evaluating the timing of the routine invasive approach was the Intracoronary Stenting With Antithrombotic Regimen Cooling-Off (ISAR-COOL) trial.26 This trial randomized patients with suspected NSTEACS to an early (⬍24 hours after anginal complaints) or a 3- to 5-day deferred invasive diagnostic strategy. Although there was no difference between groups regarding the individual end points, the combined end point of death and MI occurred significantly less in the early arm compared to the deferred strategy.26 Recently, the Timing of Intervention in Acute Coronary Syndrome (TIMACS)27 and Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndromes Randomized for an Immediate or Delayed Intervention (ABOARD)28 trials provided important information on the feasibility of a very early invasive diagnostic routine. TIMACS is clearly the largest study performed, with approximately 1,500 patients in its 2 arms. This study’s results were negative with regard to its end points. However, a subanalysis of a high-risk population, defined as having GRACE risk scores ⬎140, suggested a benefit in the early arm. The ABOARD trial28 evaluated a primary PCI approach for NSTEACS compared to elective catheterization on the next day. The trial failed to show any benefit for this approach. In addition, there appeared to be a trend toward more MIs in the early group. The influence of timing of PCI remains difficult to determine because the aforementioned trials randomized to the timing of coronary angiography, and only a portion of patients were treated with PCI (Table 2). It is likely that the influence of timing of coronary angiography is less pronounced in patients who are treated conservatively or who

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interpretation, which suggests a U-shaped curve for timeevent relation. Using potent antiplatelet and anticoagulation therapy, the early hazard is not as pronounced as in the past.30 In the acute setting, PCI is still most likely to counteract plaque passification by intracoronary manipulation, leading to a higher rate of periprocedural MI. It seems reasonable to want to treat patients with PCI after pharmacokinetic onset of the initiated medication to reduce periprocedural inflicted MI. Therefore, sufficient time is needed to allow pharmacologic stabilization, but the postponement of intervention may lead to an increase of new spontaneous events. One may expect that patients at high risk for recurrent events benefit most from revascularization soon after pharmacologic stabilization. Figure 2. The relation between timing of the early intervention and the relative risk (RR) for MI against a delayed strategy at 30-day follow-up.

eventually undergo CABG. It is clear that a fast invasive diagnostic approach has diagnostic benefits and facilitates the logistics of further treatment planning. However, the question remains: should early angiography always be followed by prompt intervention? The proper answer can be obtained only from a randomized study in which patients are randomized between immediate and delayed PCI, as was done in the OPTIMA trial.11 Although the trial was terminated early because of slow patient recruitment, it suggested the presence of an early hazard. After acute coronary angiography in 251 patients admitted with NSTEACS, this trial randomized 142 acute patients eligible for PCI to immediate (0.5 hours) or deferred (24 hours) PCI. Moreover, OPTIMA used only 1 infarct definition and included all MIs in its end point, including evolving MI at randomization. This was done because with very early PCI, periprocedural MI is hard to distinguish from a spontaneously evolving MI that started before PCI. OPTIMA showed that MI was significantly more common in patients receiving immediate PCI (Table 2).11 This difference was most likely due to an excess of periprocedural infarctions in the immediately treated group. This seems to contradict with a recently published post hoc analysis of the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial, which suggested a better outcome with urgent revascularization.29 Although this study included a large patient sample, the design of the ACUITY trial was not suited to detect the influence of timing of PCI. These observational studies are extremely liable to indication bias and should therefore be interpreted with the utmost caution. Are there any clues regarding the optimal timing of intervention that can be distilled from the data provided by the 4 trials on this topic? When it is suggested that the influence of timing of invasive therapy is the most pronounced just after an acute event, it is likely that the timing of initiation of therapy in the early invasive group will be the most important variable. In this case, a time-event relation can be estimated using the relative risk for MI at 30 days for each trial and plotted against the time of admittance to diagnostic catheterization, the latter being at least remotely related to timing of intervention. Figure 2 shows this

Revascularization Methods Although numerous clinical trials have compared PCI and CABG, few trials have compared PCI and CABG in a selected population of patients with NSTEACS.31 The Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) trial randomized patients with a NSTEACS to PCI using bare-metal stents or CABG.32 Short- and long-term mortality rates were similar, but PCI was associated with an increase in recurrent ischemia and repeat revascularization. The current guidelines recommend CABG for patients with disease of the left main coronary artery, multivessel disease, and impaired left ventricular function.1,2 Contemporary trials show nevertheless that PCI provides an alternative in patients with fewer complex coronary artery disease.33 Although the use of modern stents and scoring systems aids in the feasibility of PCI in highrisk patient groups, it remains associated with a higher rate of repeat procedures. Patients who present with ACS often show multiple coronary lesions, of which ⱖ1 is responsible for the symptoms. These so-called culprit lesions can be identified either by angiographic characteristics or by coronary territory. The latter requires the determination of the localization of ischemia. In patients with ST-elevation MIs, multivessel PCI has been associated with an increased rate of ischemic events compared to PCI of the culprit lesion alone.34 In contrast, in stable patients, no differences in events were observed.35 Although there is a lack of prospective data in patients with NSTEACS, a large registry of patients with NSTEACS treated with PCI showed multivessel revascularization to be equivalent compared with PCI of the culprit lesion alone regarding death or MI. In this registry, multivessel PCI was associated with a lower rate of repeat revascularization.36 In case of multivessel approach, fractional flow reserve guidance should be considered while selective intervention limited to flow obstructive lesions results in a decrease in adverse events.37 Future Directions In the past 20 years, the rise of invasive coronary diagnostics, interventions, and pharmacotherapies has revolutionized modern cardiology. Strategies based on different pathophysiologic assumptions such as plaque sealing38 and

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Figure 3. The use of CTA in the initial evaluation of NSTEACS. CTA was performed in a 48-year-old man presenting with chest pain. There was an intermediate probability of ACS. Multiplanar reconstruction of the left anterior descending coronary artery (LAD) showed a moderately severe mixed stenosis in the proximal LAD with evidence of superimposed thrombus (white arrow).

primary PCI11,28 have been considered. Undeniably, coronary revascularization has played a dynamic role. Future research should focus on better identification of those patients with high risk for recurrent unstable disease. Plaque composition and morphology using CTA or optical coherence tomography are being evaluated as promising new techniques.39 – 41 There is increasing evidence that the use of CTA in patients with suspected NSTEACS can provide important information on the pathophysiology of the acute event by recognizing the vulnerable plaque40 (Figure 3). When an early invasive strategy is preferred, optical coherence tomography is able to identify underlying plaque morphology and detect thrombi of different stages of organization.41 How this new insight will influence clinical decision making and whether this will alter the choice of therapy will be the subject of debate in the coming years. 1. ESC guidelines on the diagnosis and treatment of non ST-segment elevation acute coronary syndromes. Eur Heart J 2007;28:1598 –1660. 2. 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. Circulation 2007;116:e148 – e304. 3. ACC/AHA/ASE 2003 guideline update for the clinical application of echocardiography: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical Application of Echocardiography). Circulation 2003;108:1146 –1162. 4. Scirica BM. Acute coronary syndrome: emerging tools for diagnosis and risk assessment. J Am Coll Cardiol 2010;55:1403–1415. 5. Schuetz GM, Zacharopoulou NM, Schlattmann P, Dewey M. Metaanalysis: Noninvasive coronary angiography using computed tomography versus magnetic resonance imaging. Ann Intern Med 2010;152: 167–177. 6. Consensus document on coronary computed tomographic angiography ACCF/ACR/AHA/NASCI/SAIP/SCAI/SCCT 2010 expert consensus. J Am Coll Cardiol 2010;55:2663–2699.

7. Johnson KM. Extracardiac findings on cardiac computed tomography. J Am Coll Cardiol 2010;55:1566 –1568. 8. Meijboom WB, van Mieghem CA, Mollet NR, Pugliese F, Weustink AC, van Pelt N, Cademartiri F, Nieman K, Boersma E, de Jaegere P, Krestin GP, de Feyter PJ. 64-slice computed tomography coronary angiography in patients with non ST-elevation acute coronary syndrome. Heart 2007;93:1386e92. 9. Goldstein JA, Gallagher MJ, O’Neill WW, Ross MA, O’Neil BJ, Raff GL. A randomized controlled trial of multi-slice coronary computed tomography for evaluation of acute chest pain. J Am Coll Cardiol 2007;49:863– 871. 10. Roe MT, Harrington RA, Prosper DM, Pieper KS, Bhatt DL, Lincoff AM, Simoons ML, Akkerhuis M, Ohman EM, Kitt MM, Vahanian A, Ruzyllo W, Karsch K, Califf RM, Topol EJ; The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial Investigators. Clinical and therapeutic profile of patients presenting with acute coronary syndromes who do not have significant coronary artery disease. Circulation 2000;102:1101– 1106. 11. Riezebos RK, Ronner E, Ter Bals E, Slagboom T, Smits PC, ten Berg JM, Kiemeneij F, Amoroso G, Patterson MS, Suttorp MJ, Tijssen JG, Laarman GJ; OPTIMA trial. Immediate versus deferred coronary angioplasty in non-ST-elevation acute coronary syndromes. Heart 2009; 95:807– 812. 12. Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Van de Werf F, Avezum A, Goodman SG, Flather MD, Anderson FA Jr, Granger CB. Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ 2006;333: 1091. 13. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, Mautner B, Corbalan R, Radley D, Braunwald E. The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA 2000;284:835– 842. 14. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP, Van De Werf F, Avezum A, Goodman SG, Flather MD, Fox KA; Global Registry of Acute Coronary Events Investigators. Predictors of hospital mortality in the Global Registry of Acute Coronary Events. Arch Intern Med 2003;163:2345–2353. 15. Pieper KS, Gore JM, FitzGerald G, Granger CB, Goldberg RJ, Steg G, Eagle KA, Anderson FA, Budaj A, Fox KA; Global Registry of Acute Coronary Events (GRACE) Investigators. Validity of a risk-prediction tool for hospital mortality: the Global Registry of Acute Coronary Events. Am Heart J 2009;157:1097–1105. 16. Cannon CP, Weintraub WS, Demopoulos LA, Robertson DH, Gormley GJ, Braunwald E. 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. 17. Hochman JS, Boland J, Sleeper LA, Porway M, Brinker J, Col J, Jacobs A, Slater J, Miller D, Wasserman H. Current spectrum of cardiogenic shock and effect of early revascularisation on mortality: results of an international registry. Circulation 1995;91:873– 881. 18. Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999;354;708 –715. 19. Fox KA, Poole-Wilson PA, Henderson RA, Clayton TC, Chamberlain DA, Shaw TR, Wheatley DJ, Pocock SJ; Randomized Intervention Trial of Unstable Angina Investigators. Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Lancet 2002;360:743–751. 20. de Winter RJ, Windhausen F, Cornel JH, Dunselman PH, Janus CL, Bendermacher PE, Michels HR, Sanders GT, Tijssen JG, Verheugt FW; Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) Investigators. Early invasive versus selectively invasive management for acute coronary syndromes. N Engl J Med 2005;353:1095–1104. 21. Hirsch A, Windhausen F, Tijssen JG, Verheugt FW, Cornel JH, de Winter RJ; Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS) Investigators. Long-term outcome after an early invasive versus selective invasive treatment strategy in patients with

Review/Invasive Strategies for NSTEACS

22.

23.

24.

25.

26.

27.

28.

29.

30.

31.

non-ST-elevation acute coronary syndrome and elevated cardiac troponin T (the ICTUS trial): a follow-up study. Lancet 2007;369:827– 835. Damman P, Hirsch A, Windhausen F, Tijssen JG, de Winter RJ; ICTUS Investigators. A randomised comparison of an early invasive versus selective invasive management in patients with non-ST-elevation acute coronary syndrome. J Am Coll Cardiol 2010;55:858 – 864. Fox KAA, Poole-Wilson P, Clayton TC. 5-year outcome of an interventional strategy in non-ST elevation acute coronary syndrome: the British Heart Foundation RITA 3 randomised trial. Lancet 2005;366: 914 –920. Fox KA, Clayton TC, Damman P, Pocock SJ, de Winter RJ, Tijssen JG, Lagerqvist B, Wallentin L; FIR Collaboration. Long-term outcome of a routine versus selective invasive strategy in patients with nonST-segment elevation acute coronary syndrome a meta-analysis of individual patient data. J Am Coll Cardiol 2010;55:2435–2445. Fox KA, Anderson FA Jr, Dabbous OH, Steg PG, López-Sendón J, Van de Werf F, Budaj A, Gurfinkel EP, Goodman SG, Brieger D; GRACE Investigators. Intervention in acute coronary syndromes: do patients undergo intervention on the basis of their risk characteristics? The Global Registry of Acute Coronary Events (GRACE). Heart 2007;93:177–182. Neumann FJ, Kastrati A, Pogatsa-Murray G, Mehilli J, Bollwein H, Bestehorn HP, Schmitt C, Seyfarth M, Dirschinger J, Schömig A. Evaluation of prolonged antithrombotic pretreatment (“cooling-off” strategy) before intervention in patients with unstable coronary syndromes: a randomized controlled trial. JAMA 2003;290:1593–1599. Mehta SR, Granger CB, Boden WE, Steg PG, Bassand JP, Faxon DP, Afzal R, Chrolavicius S, Jolly SS, Widimsky P, Avezum A, Rupprecht HJ, Zhu J, Col J, Natarajan MK, Horsman C, Fox KA, Yusuf S; TIMACS Investigators. Early versus delayed intervention in acute coronary syndromes. N Engl J Med 2009;360:2165–2175. Montalescot G, Cayla G, Collet JP, Elhadad S, Beygui F, Le Breton H, Choussat R, Leclercq F, Silvain J, Duclos F, Aout M, Dubois-Randé JL, Barthélémy O, Ducrocq G, Bellemain-Appaix A, Payot L, Steg PG, Henry P, Spaulding C, Vicaut E; ABOARD Investigators. Immediate vs delayed intervention for acute coronary syndromes: a randomised clinical trial. JAMA 2009;302:947–954. Sorajja P, Gersh BJ, Cox DA, McLaughlin MG, Zimetbaum P, Costantini C, Stuckey T, Tcheng JE, Mehran R, Lansky AJ, Grines CL, Stone GW. Impact of delay to angioplasty in patients with acute coronary syndromes undergoing invasive management. J Am Coll Cardiol 2010; 55:1416 –1424. de Feyter PJ, Suryapranata H, Serruys PW, Beatt K, van Domburg R, van den Brand M, Tijssen JJ, Azar AJ, Hugenholtz PG. Coronary angioplasty for unstable angina: immediate and late results in 200 consecutive patients with identification of risk factors for unfavorable early and late outcome. J Am Coll Cardiol 1988;12:324 –333. Bravata DM, Gienger AL, McDonald KM, Sundaram V, Perez MV, Varghese R, Kapoor JR, Ardehali R, Owens DK, Hlatky MA. Systematic review: the comparative effectiveness of percutaneous coro-

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33.

34.

35.

36.

37.

38. 39.

40.

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nary interventions and coronary artery bypass graft surgery. Ann Intern Med 2007;147:703–716. Morrison DA, Sethi G, Sacks J, Henderson W, Grover F, Sedlis S, Esposito R, Ramanathan K, Weiman D, Sucedo J, Antakli T, Paramesh V, Pett S, Vernon S, Birjiniuk V, Welt F, Krucoff M, Wolfe W, Lucke J, Mediratta S, Booth D, Barbiere C, Lewis D. Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischaemia and risk factors for adverse outcomes with bypass: a multicenter, randomised trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME). J Am Coll Cardiol 2001;38:143–149. Serruys PW, Morice MC, Kappetein AP, Colombo A, Holmes DR, Mack MJ, Ståhle E, Feldman TE, van den Brand M, Bass EJ, Van Dyck N, Leadley K, Dawkins KD, Mohr FW. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med 2009;360:961–972. Corpus RA, House JA, Marso SP, Grantham JA, Huber KC Jr, Laster SB, Johnson WL, Daniels WC, Barth CW, Giorgi LV, Rutherford BD. Multivessel percutaneous intervention in patients with multivessel disease and acute myocardial infarction. Am Heart J 2004;148:493– 500. Ijsselmuiden AJ, Ezechiels J, Westendorp IC, Tijssen JG, Kiemeneij F, Slagboom T, van der Wieken R, Tangelder G, Serruys PW, Laarman G. Complete versus culprit vessel percutaneous coronary intervention in multivessel disease: a randomised comparison. Am Heart J 2004; 148:467– 474. Shishehbor MH, Lauer MS, Singh IM, Chew DP, Karha J, Brener SJ, Moliterno DJ, Ellis SG, Topol EJ, Bhatt DL. In unstable angina or non-ST-segment acute coronary syndrome, should patients with multivessel coronary artery disease undergo multivessel or culprit-only stenting? J Am Coll Cardiol 2007;49:849 – 854. Tonino PA, De Bruyne B, Pijls NH, Siebert U, Ikeno F, van’ t Veer M, Klauss V, Manoharan G, Engstrøm T, Oldroyd KG, Ver Lee PN, MacCarthy PA, Fearon WF; FAME Study Investigators. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213–224. Meier B. Plaque sealing by coronary angioplasty. Heart 2004;90: 1395–1398. van Velzen JE, Schuijf JD, de Graaf FR, Nucifora G, Pundziute G, Jukema JW, Schalij MJ, Kroft LJ, de Roos A, Reiber JH, van der Wall EE, Bax JJ. Plaque type and composition as evaluated non-invasively by MSCT angiography and invasively by VH IVUS in relation to the degree of stenosis. Heart 2009;95:1990 –1996. Russo V, Zavalloni A, Bacchi Reggiani ML, Buttazzi K, Gostoli V, Bartolini S, Fattori R. Incremental prognostic value of coronary CT angiography in patients with suspected coronary artery disease. Circ Cardiovasc Imaging 2010;3:351–359. Toutouzas K, Karanasos A, Stefanadis C. Multiple plaque morphologies assessed by optical coherence tomography in a patient with acute coronary syndrome. Heart 2010;96:1335–1336.