FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 353:1095-1104 September 15, 2005 Number 11 Next

Abstract PDF PDA Full Text PowerPoint Slide Set Editorial by Boden, W. E. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Current guidelines recommend an early invasive strategy for patients who have acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level. However, randomized trials have not shown an overall reduction in mortality, and the reduction in the rate of myocardial infarction in previous trials has varied depending on the definition of myocardial infarction.

Methods We randomly assigned 1200 patients with acute coronary syndrome without ST-segment elevation who had chest pain, an elevated cardiac troponin T level (0.03 µg per liter), and either electrocardiographic evidence of ischemia at admission or a documented history of coronary disease to an early invasive strategy or to a more conservative (selectively invasive) strategy. Patients received aspirin daily, enoxaparin for 48 hours, and abciximab at the time of percutaneous coronary intervention. The use of clopidogrel and intensive lipid-lowering therapy was recommended. The primary end point was a composite of death, nonfatal myocardial infarction, or rehospitalization for anginal symptoms within one year after randomization.

Results The estimated cumulative rate of the primary end point was 22.7 percent in the group assigned to early invasive management and 21.2 percent in the group assigned to selectively invasive management (relative risk, 1.07; 95 percent confidence interval, 0.87 to 1.33; P=0.33). The mortality rate was the same in the two groups (2.5 percent). Myocardial infarction was significantly more frequent in the group assigned to early invasive management (15.0 percent vs. 10.0 percent, P=0.005), but rehospitalization was less frequent in that group (7.4 percent vs. 10.9 percent, P=0.04).

Conclusions We could not demonstrate that, given optimized medical therapy, an early invasive strategy was superior to a selectively invasive strategy in patients with acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level.

Despite these recommendations, it is not clear that an early invasive strategy reduces mortality in this setting. A reduction in mortality was shown in the FRISC II study, but only among men. Such a reduction was not seen in any of the other studies. In addition, the reduction in the incidence of myocardial infarction associated with an early invasive strategy in these studies depended on the definition of myocardial infarction. Moreover, recent advances in medical therapy, such as the early use of clopidogrel and intensive lipid-lowering therapy, have been shown to improve the prognosis in patients with acute coronary syndromes.^9,10 These therapies have not been tested in trials of early invasive strategies. Therefore, we conducted the present study to test the hypothesis that an early invasive strategy is superior to a selectively invasive strategy for patients who have acute coronary syndromes without ST-segment elevation and with an elevated cardiac troponin T level.

Methods

Study Population and Study Design

Between July 2001 and August 2003, 1200 patients were enrolled from 42 Dutch hospitals, 12 of which were high-volume centers with facilities for percutaneous coronary intervention and on-site cardiac surgery. The protocol was approved by all the local institutional review boards. All patients gave written informed consent. The trial was funded by a combination of sources. The sponsors had no involvement in the design of the study, data collection or analysis, or the writing of the manuscript.

Eligible patients had to have all three of the following: symptoms of ischemia that were increasing or occurred at rest, with the last episode occurring no more than 24 hours before randomization; an elevated cardiac troponin T level (0.03 µg per liter); and either ischemic changes as assessed by electrocardiography (defined as ST-segment depression or transient ST-segment elevation exceeding 0.05 mV, or T-wave inversion of 0.2 mV in two contiguous leads) or a documented history of coronary artery disease as evidenced by previous myocardial infarction, findings on previous coronary angiography, or a positive exercise test. Exclusion criteria were an age younger than 18 years or older than 80 years, myocardial infarction with ST-segment elevation in the past 48 hours, an indication for primary percutaneous coronary intervention or fibrinolytic therapy, hemodynamic instability or overt congestive heart failure, the use of oral anticoagulant drugs in the past 7 days, fibrinolytic treatment within the past 96 hours, percutaneous coronary intervention within the past 14 days, a contraindication to treatment with percutaneous coronary intervention or glycoprotein IIb/IIIa inhibitors, recent trauma or risk of bleeding, hypertension despite treatment (i.e., systolic pressure >180 mm Hg or diastolic pressure >100 mm Hg), weight greater than 120 kg, or inability to give informed consent.

Optimized Medical Therapy

The protocol specified that patients receive 300 mg of aspirin at the time of randomization, followed by at least 75 mg daily indefinitely, and enoxaparin (1 mg per kilogram of body weight, to a maximum of 80 mg) twice daily subcutaneously for at least 48 hours. Patients already started on unfractionated heparin were switched to enoxaparin immediately after randomization. The early use of clopidogrel (300 mg immediately, followed by 75 mg daily) in combination with aspirin was recommended to the investigators after the drug was approved in 2002 for the indication of acute coronary syndromes.⁹

All interventional procedures during the initial hospital phase were performed with the use of abciximab, given as a bolus dose of 0.25 mg per kilogram, followed by an infusion of 0.125 µg per kilogram per minute for 12 hours, and started 10 to 60 minutes before the first balloon inflation.¹¹ Abciximab was also available for use in patients who subsequently underwent percutaneous revascularization. The protocol recommended intensive lipid-lowering therapy, preferably 80 mg of atorvastatin daily or the equivalent, started as soon as possible after randomization and continued indefinitely. The level of the MB isoform of creatine kinase (CK-MB) was measured at 6-hour intervals during the first period of 24 hours or more after admission, after each new clinical episode of ischemia, and after each percutaneous revascularization procedure.

Treatment Strategy

Patients were randomly assigned to an early invasive strategy or a selectively invasive strategy with the use of a central telephone system. Permuted-block randomization was performed, with stratification according to site, with block size randomly chosen to be four, six, or eight. Patients assigned to the early invasive strategy were scheduled to undergo angiography within 24 to 48 hours after randomization and percutaneous coronary intervention when appropriate on the basis of the coronary anatomy. Coronary-artery bypass grafting was recommended in patients with extensive three-vessel disease or severe left main-stem disease and was to be performed as soon as possible during the initial hospitalization period.

Patients assigned to the selectively invasive strategy were treated medically. These patients were scheduled to undergo angiography and subsequent revascularization only if they had refractory angina despite optimal medical treatment, hemodynamic or rhythmic instability, or clinically significant ischemia on the predischarge exercise test. Coronary angiography and revascularization after the initial hospital phase were performed if severe anginal symptoms (i.e., Canadian Cardiovascular Society [CCS] class III or IV) persisted despite optimal antianginal medication or if ischemia was documented on subsequent testing. Follow-up outpatient visits occurred at 1, 6, and 12 months after randomization.

End Points

The primary end point was a composite of death, recurrent myocardial infarction, or rehospitalization for angina within one year after randomization. Death was defined as death from any cause. Myocardial infarction was defined as documented myocardial necrosis, occurring either spontaneously or in the setting of percutaneous intervention, according to the recommendations of the Joint European Society of Cardiology–American College of Cardiology Committee for the Redefinition of Myocardial Infarction.¹² Myocardial necrosis was defined by an elevation in the CK-MB level above the upper limit of normal. In the event of an elevated CK-MB level at randomization, recurrent myocardial infarction during the first 48 hours was diagnosed when there was a 50 percent decrease from a previous peak value, followed by a subsequent rise to a level exceeding the upper limit of normal. A myocardial infarction in the setting of coronary-artery bypass grafting required the occurrence of electrocardiographic evidence of new Q waves.

Major bleeding not related to coronary-artery bypass grafting during the index admission was defined by at least one of the following: fatal bleeding, intracranial bleeding, a need for blood transfusion, a decrease of 3 mmol per liter (4.8 g per deciliter) or more in hemoglobin levels, and bleeding resulting in hemodynamic compromise. All end points were adjudicated by members of an independent clinical end-points committee, who were unaware of the treatment assignments of the patients.

Statistical Analysis

We calculated that, given a 21 percent incidence of the primary end point in the group assigned to an early invasive strategy, 1200 patients would be needed to provide the study with 80 percent power to detect a relative risk reduction of 25 percent between the two groups, at an alpha level of 0.05. Continuous variables with normal distributions are expressed as means ±SD and were compared with the use of an unpaired Student's t-test. Categorical variables were compared with the use of Fisher's exact test or the chi-square test, where appropriate. All reported P values are two-sided and not adjusted for multiple testing.

Event rates at one year were estimated with the Kaplan–Meier method.¹³ Relative risks were calculated by dividing the Kaplan–Meier estimated rate of an event at one year in the early-invasive-strategy group by that in the group assigned to a selectively invasive strategy. The 95 percent confidence interval for the relative risk was calculated with the use of the standard errors from the Kaplan–Meier curve. The significance of differences in event rates between treatment groups was assessed with the use of the log-rank test. Data on patients who were lost to follow-up were censored at the time of the last contact.

Results

A total of 604 patients were randomly assigned to the early invasive strategy and 596 patients to the selectively invasive strategy. Baseline characteristics are shown in Table 1. The median age was 62 years, about three quarters of the patients were male, and 14 percent had diabetes. Cardiac catheterization was performed during the initial hospitalization in 98 percent of patients in the early-invasive-strategy group and 53 percent in the selectively-invasive-strategy group, and in 99 percent and 67 percent, respectively, within one year (Table 2). Within one year, 79 percent of the patients in the early-invasive-strategy group had undergone revascularization, as compared with 54 percent in the selectively-invasive-strategy group. Eighty-eight percent of the percutaneous coronary intervention procedures in both treatment groups combined involved the placement of at least one stent. Medical therapy at discharge was similar between the group assigned to an early invasive strategy and the group assigned to a selectively invasive strategy, except for the use of clopidogrel (61 percent vs. 49 percent, respectively). The incidence of statin use at discharge was very high in both groups (90 percent and 94 percent, respectively).

View this table: [in this window] [in a new window]   Table 1. Baseline Characteristics of the Patients.

 

View this table: [in this window] [in a new window]   Table 2. Cardiac Procedures within Two Days after Randomization, during Initial Hospitalization, and within One Year, According to Study Group.

 
Primary End Point

Six patients were lost to follow-up before one year. A total of 263 patients (137 patients in the early-invasive-strategy group and 126 patients in the selectively-invasive-strategy group) reached the primary end point. Kaplan–Meier curves for the primary end point are shown in Figure 1. The estimated one-year cumulative event rate was 22.7 percent in the early-invasive-strategy group and 21.2 percent in the group assigned to a selectively invasive strategy (relative risk, 1.07; 95 percent confidence interval, 0.87 to 1.33; P=0.33) (Table 3). One-year mortality was 2.5 percent in both groups (relative risk, 0.99; 95 percent confidence interval, 0.49 to 2.00; P=0.97). The cumulative risk of myocardial infarction within one year after randomization was significantly higher in the early-invasive-strategy group (15.0 percent vs. 10.0 percent; relative risk, 1.50; 95 percent confidence interval, 1.10 to 2.04; P=0.005). Rehospitalization was less frequent in the early-invasive-strategy group (7.4 percent vs. 10.9 percent; relative risk, 0.68; 95 percent confidence interval, 0.47 to 0.98; P=0.04).

View larger version (20K): [in this window] [in a new window]   Figure 1. Kaplan–Meier Estimates of the Cumulative Rate of the Composite Primary End Point of Death, Nonfatal Myocardial Infarction, or Rehospitalization for Anginal Symptoms within One Year. The rate of a composite primary end point within one year was 22.7 percent in the group assigned to an early invasive strategy and 21.2 percent in the group assigned to a selectively invasive strategy (relative risk, 1.07; 95 percent confidence interval, 0.87 to 1.33; P=0.33).

 

View this table: [in this window] [in a new window]   Table 3. Cumulative Rate of the Composite Primary End Point and Its Components within One Year after Randomization.

 
Several baseline clinical features were examined for potential effects in a subgroup analysis. The relative risks were not different among the major subgroups defined according to age, sex, the presence or absence of diabetes mellitus, the presence or absence of ST-segment deviation, or the level of cardiac troponin T (Figure 2).

View larger version (30K): [in this window] [in a new window]   Figure 2. Estimated Rates and Relative Risks of the Composite Primary End Point of Death, Nonfatal Myocardial Infarction, or Rehospitalization for Anginal Symptoms within One Year, According to Subgroup. The frequency of the primary end points within one year after randomization was estimated from the Kaplan–Meier curves.

 
Myocardial Infarction

Categories of infarct size according to peak CK-MB level are shown in Table 3. The rate of myocardial infarction among patients with a peak CK-MB level one to three times the upper limit of normal was significantly higher in the early-invasive-strategy group than in the group assigned to a selectively invasive strategy (7.2 percent vs. 4.6 percent, P=0.05). The incidence of myocardial infarction related to percutaneous coronary intervention or coronary-artery bypass grafting was also significantly higher in the early-invasive-strategy group (11.3 percent vs. 5.4 percent, P=0.001). To compare our results with those of previous trials, we applied the definitions of myocardial infarction from the FRISC II⁴ and the TACTICS–TIMI 18⁵ studies to our data (Table 3). Applying these definitions lowered the rate of infarction. However, the relative risks remained essentially unaltered, and there were no significant differences in the rate of the composite primary end point between the groups, irrespective of the definition of infarction applied.

Other Secondary End Points

The percentage of patients free from anginal symptoms was similar in the early-invasive-strategy group and the group assigned to a selectively invasive strategy (86 percent and 87 percent, respectively). Moreover, the incidence of angina, defined as CCS class I to IV, was similar in the two groups (data not shown). Major bleeding not related to coronary-artery bypass grafting during the index admission occurred in 19 patients (3.1 percent) in the early-invasive-strategy group, as compared with 10 patients (1.7 percent) in the group assigned to a selectively invasive strategy.

Discussion

This study did not show that an early invasive strategy was superior to a selectively invasive strategy in patients who had an acute coronary syndrome without ST-segment elevation and who had an elevated cardiac troponin T level. Mortality within one year was low (2.5 percent in both groups), despite the fact that these patients were all considered at high risk. The incidence of myocardial infarction was significantly higher in the early-invasive-strategy group, particularly during hospitalization, confirming the finding of the FRISC II researchers⁴ that there is an early hazard associated with early revascularization. The incidence of the primary end point was 22.7 percent in the early-invasive-strategy group, but 21.2 percent in the group assigned to a selectively invasive strategy, which was lower than anticipated. There was no significant difference in the frequency of the primary end point among subgroups defined according to age, sex, the presence or absence of diabetes mellitus, the presence or absence of ST-segment deviation, or the level of cardiac troponin T.

Comparing the results of the present study with those of previous trials is not straightforward, owing to differences in study design, in the risk profile of patients included, in antithrombotic therapy, and in the definition of end points, in particular the definition of myocardial infarction; changes in the practice of invasive therapy (especially the use of stents and glycoprotein IIb/IIIa inhibitors); and the observed contrast between strategies in the rate and timing of revascularization. There are several possible explanations for the observed differences in outcome between the present study and previous trials.

First, revascularization rates were high in the two groups in our study (76 percent in the early-invasive-strategy group and 40 percent in the selectively-invasive-strategy group during the initial hospitalization, and 79 percent and 54 percent, respectively, within 1 year after randomization) as compared with those in TIMI-IIIb (64 percent vs. 58 percent at 1 year), VANQWISH (44 percent vs. 33 percent at 23 months), FRISC II (71 percent vs. 9 percent at 10 days, and 77 percent vs. 37 percent at 6 months), TACTICS–TIMI 18 (61 percent vs. 44 percent at 6 months), and RITA-3 (44 percent vs. 10 percent during the index admission, and 57 percent vs. 28 percent within 1 year).¹⁴ As in the VANQWISH trial, all patients in our study had evidence of myocardial necrosis, as compared with 58 percent with an elevated troponin level in FRISC II, 54 percent in TACTICS–TIMI 18, and 75 percent in RITA-3. The fact that all patients in the present study were at high risk (as evidenced by an elevated troponin level) may explain the earlier and more frequent revascularization in the group assigned to a selectively invasive strategy in our study. The 40 percent rate of revascularization during the initial hospitalization in the group assigned to a selectively invasive strategy in our study compares well with the 48 percent rate of revascularization in patients with acute coronary syndromes who were admitted to centers with catheterization facilities in the global registry of acute coronary events (the GRACE registry), which reflects real-world clinical practice.¹⁵

Second, as in FRISC II, most myocardial infarctions in the early-invasive-strategy group in our study were procedure-related.¹⁶ The higher incidence of myocardial infarction in this group is driven in large part by relatively small infarctions related to percutaneous coronary intervention that were detected with carefully timed and frequent measurements of CK-MB levels. Moreover, we applied the Joint European Society of Cardiology – American College of Cardiology definitions of spontaneous and percutaneous coronary intervention–related myocardial infarction (peak CK-MB level, greater than the upper limit of normal).¹² Different cutoff levels for infarctions related to percutaneous coronary intervention were used in FRISC II (CK-MB level, >1.5 times the upper limit of normal), TACTICS–TIMI 18 (CK-MB level, 3 times the upper limit of normal), and RITA-3 and Superior Yield of the New Strategy of Enoxaparin, Revascularization, and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) (CK-MB level, 2 times the upper limit of normal). The incidence of myocardial infarction in the early-invasive-strategy group in our study (15.0 percent at 1 year; median time to percutaneous coronary intervention, 23 hours) was similar to that in the recent SYNERGY trial (11.7 percent at 30 days; median time to percutaneous coronary intervention, 23 hours), in which an early-intervention strategy was used.¹⁷

The prognostic implications of periprocedural myocardial damage are controversial, but some reports suggest that the prognosis of patients with such injury should be regarded as similar to that of patients with spontaneous necrosis.^16,18,19 To determine whether the increased incidence of procedure-related myocardial infarction in the early-invasive-strategy group in our study eventually results in a worse prognosis will require long-term follow-up. Regardless of the definition of myocardial infarction in our study, we could not demonstrate a significant difference in the incidence of the composite primary end point between the two treatment strategies.

Third, the incidence of myocardial infarction in the group assigned to a selectively invasive strategy was lower than expected. We incorporated recent advances in background medical therapy, such as the use of abciximab at the time of percutaneous coronary intervention procedures, the early use of clopidogrel, and intensive lipid-lowering therapy, which have been shown to improve outcomes in patients who have acute coronary syndromes without ST-segment elevation.^10,20 This may partially explain the lower-than-expected event rate in the group assigned to a selectively invasive strategy.

Finally, all procedures were performed in high-volume centers with facilities for cardiac surgery on site, resulting in a low overall mortality, including a low mortality related to coronary-artery bypass grafting. In our view, advances in background medical therapy in combination with better detection of myocardial infarctions with frequent, carefully timed measurements of CK-MB levels best explain the differences between our results and those of previous trials.

The 2003 European Society of Cardiology guidelines were published during the study enrollment period. Physicians familiar with the guidelines would probably be inclined to favor performing angiography in most patients with an elevated cardiac troponin T level. As a result, physicians participating in our study might have enrolled lower-risk patients than would otherwise have been included. However, baseline characteristics suggest that we studied a high-risk population, with more than one third of the patients already taking aspirin, more than half having ischemic changes as assessed by electrocardiography, and all having an elevated cardiac troponin T level as confirmed with core laboratory analysis.

We did not find the expected 25 percent reduction in the cumulative rate of the primary end point with an early invasive strategy as compared with a selectively invasive strategy. As a result, the confidence interval around the relative risk of the composite end point of death, myocardial infarction, or rehospitalization for angina was 0.87 to 1.33, corresponding to a possible reduction in risk of 13 percent (or an increase in risk of 33 percent) with an early invasive strategy. However, the point estimate for the relative risk (1.07) actually favors the selectively invasive approach, and even the most substantial advantage of early invasive management consistent with our data is much less than that estimated in previous large trials.

Among patients with acute coronary syndromes without ST-segment elevation who have an elevated cardiac troponin T level, we could not demonstrate that an early invasive strategy was superior to a selectively invasive strategy. These results were obtained with the use of contemporary medical therapy that included low-molecular-weight heparin, glycoprotein IIb/IIIa inhibition at the time of percutaneous procedures, clopidogrel, and intensive lipid-lowering therapy.

Supported by the Interuniversity Cardiology Institute of the Netherlands, the Working Group on Cardiovascular Research in the Netherlands, and educational grants from Eli Lilly, Sanofi-Synthelabo, Aventis, Pfizer, and Medtronic.

Dr. Michels reports having received grant support from Eli Lilly NL, and Dr. Verheugt consulting fees and lecture fees from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Merck, and Bayer AG.

We are indebted to Roche Diagnostics in the Netherlands for providing the device for the bedside cardiac troponin T measurements (Cardiac Reader) and the reagents for core laboratory troponin T measurements; to all the investigators and coordinators of the ICTUS trial; to all the medical and nursing staff in the recruitment and intervention centers who made the trial possible; to Karla Mulder for database management; to Alexander Hirsch, Marc van der Zee, Margriet Klees, and Wilma van der Wateren for data collection and analysis; to Jan van Straalen and Johan Fischer for invaluable assistance with laboratory measurements; and to all the patients who participated in the trial.

^* The ICTUS trial investigators are listed in the Appendix.

Source Information

From the Academisch Medisch Centrum, Amsterdam (R.J.W., F.W., G.T.S., J.G.P.T.); Medisch Centrum Alkmaar, Alkmaar (J.H.C.); Amphia Ziekenhuizen, Breda (P.H.J.M.D.); WestFriesGasthuis, Hoorn (C.L.J.); Elkerliek Ziekenhuis, Helmond (P.E.F.B.); Catharina Ziekenhuis, Eindhoven (H.R.M.); and Universitair Medisch Centrum St. Radboud, Nijmegen (F.W.A.V.) — all in the Netherlands.

Address reprint requests to Dr. de Winter at the Department of Cardiology, B2-137, Academic Medical Center, Meibergdreef 9, P.O. Box 22660, 1100 DD Amsterdam, the Netherlands, or at r.j.dewinter{at}amc.uva.nl.

References

1. Hamm CW, Braunwald E. A classification of unstable angina revisited. Circulation 2000;102:118-122. [Free Full Text]
2. Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction: results of the TIMI IIIB trial. Circulation 1994;89:1545-1556. [Free Full Text]
3. Boden WE, O'Rourke RA, Crawford MH, et al. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. N Engl J Med 1998;338:1785-1792. [Erratum, N Engl J Med 1998;339:1091.] [Free Full Text]
4. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. Lancet 1999;354:708-715. [CrossRef][Web of Science][Medline]
5. 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. [Free Full Text]
6. Fox KA, Poole-Wilson PA, Henderson RA, et al. 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. [CrossRef][Web of Science][Medline]
7. Bertrand ME, Simoons ML, Fox KA, et al. Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 2002;23:1809-1840. [Erratum, Eur Heart J 2003;24:485, 1174-5.] [Free Full Text]
8. 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. [Free Full Text]
9. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502. [Erratum, N Engl J Med 2001;345:1506, 1716.] [Free Full Text]
10. 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. [Free Full Text]
11. Topol EJ, Moliterno DJ, Herrmann HC, et al. Comparison of two platelet glycoprotein IIb/IIIa inhibitors, tirofiban and abciximab, for the prevention of ischemic events with percutaneous coronary revascularization. N Engl J Med 2001;344:1888-1894. [Free Full Text]
12. Alpert JS, Thygesen K, Antman E, Bassand JP. 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. [Erratum, J Am Coll Cardiol 2001;37:973.] [Free Full Text]
13. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-481. [CrossRef][Web of Science]
14. Boden WE. "Routine invasive" versus "selective invasive" approaches to non-ST-segment elevation acute coronary syndromes management in the post-stent/platelet inhibition era. J Am Coll Cardiol 2003;41:Suppl:113S-122S. [Free Full Text]
15. Van de Werf F, Gore JM, Avezum A, et al. Access to catheterisation facilities in patients admitted with acute coronary syndrome: multinational registry study. BMJ 2005;330:441-447. [Free Full Text]
16. Lagerqvist B, Husted S, Kontny F, et al. A long-term perspective on the protective effects of an early invasive strategy in unstable coronary artery disease: two-year follow-up of the FRISC-II invasive study. J Am Coll Cardiol 2002;40:1902-1914. [Free Full Text]
17. 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. [Free Full Text]
18. Akkerhuis KM, Alexander JH, Tardiff BE, et al. Minor myocardial damage and prognosis: are spontaneous and percutaneous coronary intervention-related events different? Circulation 2002;105:554-556. [Free Full Text]
19. Roe MT, Mahaffey KW, Kilaru R, et al. Creatine kinase-MB elevation after percutaneous coronary intervention predicts adverse outcomes in patients with acute coronary syndromes. Eur Heart J 2004;25:313-321. [Free Full Text]
20. Ferguson JJ, Antman EM, Bates ER, et al. Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study. Am Heart J 2003;146:628-634. [CrossRef][Web of Science][Medline]

The following investigators and research coordinators, all in the Netherlands, participated in the ICTUS trial (total number of patients recruited are indicated in parentheses): Academisch Medisch Centrum, Amsterdam (105) — R.J.G. Peters; Amphia Ziekenhuis, Breda (101) — P.H.J.M. Dunselman; Universitair Medisch Centrum St. Radboud, Nijmegen (78) — F.W.A. Verheugt; Westfries Gasthuis, Hoorn (74) — C.L. Janus; Medisch Centrum Alkmaar, Alkmaar (72) — V. Umans; Elkerliek Ziekenhuis, Helmond (65) — P.E.F. Bendermacher; Catharina Ziekenhuis, Eindhoven (59) — H.R. Michels; Flevoziekenhuis, Almere (48) — A. Sadée; Canisius-Wilhelmina, Nijmegen (46) — D. Hertzberger; Maasziekenhuis, Boxmeer (40) — J. Peters; Ziekenhuis Hilversum, Hilversum (40) — P.A.R.M. de Miliano; Oosterschelde Ziekenhuis, Goes (38) — A.H. Liem; Rijnstate Ziekenhuis, Arnhem (38) — R. Tjon Joe Gin; Christelijk Ziekenhuis Nij Smellinghe, Drachten (36) — M. van der Linde; Deventer Ziekenhuis, Deventer (36) — D. Lok; Ziekenhuis Gooi-Noord, Blaricum (35) — G. Hoedemaker; Boven IJ Ziekenhuis, Amsterdam (28) — M. Pieterse; Scheperziekenhuis, Emmen (27) — L. van den Merkhof; Jeroen Bosch Ziekenhuis, Den Bosch (25) — M. Daniëls; Groene Hart Ziekenhuis, Gouda (20) — M. van Hessen; St. Elisabeth Ziekenhuis, Tilburg (19) — W. Hermans; Slotervaart Ziekenhuis, Amsterdam (18) — C.E. Schotborgh; AZM, Maastricht (18) — C. de Zwaan; Diakonessenhuis, Utrecht (17) — A. Bredero; Universitair Medisch Centrum, Utrecht (17) — P. de Jaegere; Kennemer Gasthuis, Haarlem (14) — M. Janssen; Medisch Spectrum Twente, Enschede (11) — J. Louwerenburg; St. Franciscus, Rotterdam (11) — M. Veerhoek; LUMC, Leiden (11) — M. Schalij; Gemini Ziekenhuis, Den Helder (10) — A. de Porto; UMCG, Groningen (10) — F. Zijlstra; Tweesteden Ziekenhuis, Tilburg (10) — J. Winter; Erasmus MC, Rotterdam (8) — P. de Feyter; Ziekenhuis Leyenburg Den Haag (7) — R. Robles de Medina; Reinier de Graaf Gasthuis, Delft (6) — P. Withagen; Bronovo Ziekenhuis, Den Haag (5) — M. Sedney; Maxima Medisch Centrum, Veldhoven (4) — H. Thijssen; Rijnland Ziekenhuis, Leiderdorp (3) — C. van Rees; Streekziekenhuis Zevenaar, Zevenaar (2) — P. van den Bergh; VUMC, Amsterdam (1) — C. de Cock; Isala klinieken, Zwolle — A. van 't Hof; St. Antonius Ziekenhuis, Nieuwegein — M.J. Suttorp; Trial Steering Committee — R.J. de Winter (chair), F. Windhausen, J.H. Cornel, J.G.P. Tijssen, F.W.A. Verheugt, P.H.J.M. Dunselman, P.J. de Feyter, H.R. Michels; Executive Committee — R.J. de Winter, F. Windhausen, J.G.P. Tijssen; End Point Adjudication Committee — D. Düren, K. Liem; Data Center and Monitoring — Academisch Medisch Centrum, Amsterdam; Clinical Chemistry Core Laboratory — Academisch Medisch Centrum, Amsterdam, Laboratory of Clinical Chemistry, G.T.B. Sanders, J. Fischer, J. van Straalen.

Abstract PDF PDA Full Text PowerPoint Slide Set Editorial by Boden, W. E. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

Related Letters:

Management of Acute Coronary Syndromes
Tarantini G., Ramondo A., Iliceto S., Newby D. E., Fox K. A., Ionescu A., Garg A., Spaulding C., Varenne O., Weber S., Costantino G., Raggi F., Montano N., Garcia-Pavia P., Aguiar-Souto P., Silva-Melchor L., de Winter R. J., Windhausen F., Tijssen J. G.P., Boden W. E.
Extract | Full Text | PDF  
N Engl J Med 2005; 353:2714-2718, Dec 22, 2005. Correspondence

This article has been cited by other articles:

• Rothman, M., De Palma, R. (2009). Delays in angiography may cost lives. Heart 95: 1815-1817 [Full Text]  
• Kumar, A., Cannon, C. P. (2009). Acute Coronary Syndromes: Diagnosis and Management, Part I. Mayo Clin Proc. 84: 917-938 [Abstract] [Full Text]  
• Montalescot, G., Cayla, G., Collet, J.-P., Elhadad, S., Beygui, F., Le Breton, H., Choussat, R., Leclercq, F., Silvain, J., Duclos, F., Aout, M., Dubois-Rande, J.-L., Barthelemy, O., Ducrocq, G., Bellemain-Appaix, A., Payot, L., Steg, P.-G., Henry, P., Spaulding, C., Vicaut, E., for the ABOARD Investigators, (2009). Immediate vs Delayed Intervention for Acute Coronary Syndromes: A Randomized Clinical Trial. JAMA 302: 947-954 [Abstract] [Full Text]  
• Prasad, A., Gersh, B. J., Bertrand, M. E., Lincoff, A. M., Moses, J. W., Ohman, E. M., White, H. D., Pocock, S. J., McLaurin, B. T., Cox, D. A., Lansky, A. J., Mehran, R., Stone, G. W. (2009). Prognostic significance of periprocedural versus spontaneously occurring myocardial infarction after percutaneous coronary intervention in patients with acute coronary syndromes: an analysis from the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) trial.. J Am Coll Cardiol 54: 477-486 [Abstract] [Full Text]  
• Berry, C., Pieper, K. S., White, H. D., Solomon, S. D., Van de Werf, F., Velazquez, E. J., Maggioni, A. P., Califf, R. M., Pfeffer, M. A., McMurray, J. J.V. (2009). Patients with prior coronary artery bypass grafting have a poor outcome after myocardial infarction: an analysis of the VALsartan in acute myocardial iNfarcTion trial (VALIANT). Eur Heart J 30: 1450-1456 [Abstract] [Full Text]  
• Charytan, D. M., Wallentin, L., Lagerqvist, B., Spacek, R., De Winter, R. J., Stern, N. M., Braunwald, E., Cannon, C. P., Choudhry, N. K. (2009). Early Angiography in Patients with Chronic Kidney Disease: A Collaborative Systematic Review. CJASN 4: 1032-1043 [Abstract] [Full Text]  
• Windhausen, F., Hirsch, A., Fischer, J., van der Zee, P. M., Sanders, G. T., van Straalen, J. P., Cornel, J. H., Tijssen, J. G.P., Verheugt, F. W.A., de Winter, R. J., for the Invasive versus Conservative Treatment in, (2009). Cystatin C for Enhancement of Risk Stratification in Non-ST Elevation Acute Coronary Syndrome Patients with an Increased Troponin T. Clin. Chem. 55: 1118-1125 [Abstract] [Full Text]  
• Mehta, S. R., Granger, C. B., Boden, W. E., Steg, P. G., Bassand, J.-P., Faxon, D. P., Afzal, R., Chrolavicius, S., Jolly, S. S., Widimsky, P., Avezum, A., Rupprecht, H.-J., Zhu, J., Col, J., Natarajan, M. K., Horsman, C., Fox, K. A.A., Yusuf, S., the TIMACS Investigators, (2009). Early versus Delayed Invasive Intervention in Acute Coronary Syndromes. NEJM 360: 2165-2175 [Abstract] [Full Text]  
• Riezebos, R K, Ronner, E, ter Bals, E, Slagboom, T, Smits, P C, ten Berg, J M, Kiemeneij, F, Amoroso, G, Patterson, M S, Suttorp, M J, Tijssen, J G P, Laarman, G J, for the OPTIMA trial, (2009). Immediate versus deferred coronary angioplasty in non-ST-segment elevation acute coronary syndromes. Heart 95: 807-812 [Abstract] [Full Text]  
• Potsis, T. Z., Katsouras, C., Goudevenos, J. A. (2009). Avoiding and Managing Bleeding Complications in Patients With Non-ST-Segment Elevation Acute Coronary Syndromes. ANGIOLOGY 60: 148-158 [Abstract]  
• Hirsch, A., Windhausen, F., Tijssen, J. G.P., Oude Ophuis, A. J.M., van der Giessen, W. J., van der Zee, P. M., Cornel, J. H., Verheugt, F. W.A., de Winter, R. J., for the Invasive versus Conservative Treatment in, (2009). Diverging associations of an intended early invasive strategy compared with actual revascularization, and outcome in patients with non-ST-segment elevation acute coronary syndrome: the problem of treatment selection bias. Eur Heart J 30: 645-654 [Abstract] [Full Text]  
• Swahn, E., Alfredsson, J., Afzal, R., Budaj, A., Chrolavicius, S., Fox, K., Jolly, S., Mehta, S. R., de Winter, R., Yusuf, S. (2009). Early invasive compared with a selective invasive strategy in women with non-ST-elevation acute coronary syndromes: a substudy of the OASIS 5 trial and a meta-analysis of previous randomized trials. Eur Heart J 0: ehp009v1-10 [Abstract] [Full Text]  
• Swanson, N, Montalescot, G, Eagle, K A, Goodman, S G, Huang, W, Brieger, D, Devlin, G, for the GRACE Investigators, (2009). Delay to angiography and outcomes following presentation with high-risk, non-ST-elevation acute coronary syndromes: results from the Global Registry of Acute Coronary Events. Heart 95: 211-215 [Abstract] [Full Text]  
• Hollenberg, S. M. (2009). Acute Coronary Syndromes. ACCP Crit Care Med Brd Rev 20: 129-144 [Full Text]  
• Hamm, C. W., Möllmann, H., Bassand, J.-P., van de Werf, F. (2009). CHAPTER 16 Acute Coronary Syndromes. ESC Textbook of Cardiovascular Medicine 2: med-9780199566990-chapter-med-9780199566990-chapter [Abstract] [Full Text]  
• Ho, P. M., Peterson, P. N., Masoudi, F. A. (2008). Evaluating the Evidence: Is There a Rigid Hierarchy?. Circulation 118: 1675-1684 [Full Text]  
• Nallamothu, B. K., Hayward, R. A., Bates, E. R. (2008). Beyond the Randomized Clinical Trial: The Role of Effectiveness Studies in Evaluating Cardiovascular Therapies. Circulation 118: 1294-1303 [Full Text]  
• Chan, M. Y., Mahaffey, K. W., Sun, L. J., Pieper, K. S., White, H. D., Aylward, P. E., Ferguson, J. J., Califf, R. M., Roe, M. T. (2008). Prevalence, Predictors, and Impact of Conservative Medical Management for Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Who Have Angiographically Documented Significant Coronary Disease. J Am Coll Cardiol Intv 1: 369-378 [Abstract] [Full Text]  
• O'Donoghue, M., Boden, W. E., Braunwald, E., Cannon, C. P., Clayton, T. C., de Winter, R. J., Fox, K. A. A., Lagerqvist, B., McCullough, P. A., Murphy, S. A., Spacek, R., Swahn, E., Wallentin, L., Windhausen, F., Sabatine, M. S. (2008). Early Invasive vs Conservative Treatment Strategies in Women and Men With Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction: A Meta-analysis. JAMA 300: 71-80 [Abstract] [Full Text]  
• Maddox, T. M., Reid, K. J., Spertus, J. A., Mittleman, M., Krumholz, H. M., Parashar, S., Ho, P. M., Rumsfeld, J. S. (2008). Angina at 1 Year After Myocardial Infarction: Prevalence and Associated Findings. Arch Intern Med 168: 1310-1316 [Abstract] [Full Text]  
• Henriksson, M, Epstein, D M, Palmer, S J, Sculpher, M J, Clayton, T C, Pocock, S J, Henderson, R A, Buxton, M J, Fox, K A A (2008). The cost-effectiveness of an early interventional strategy in non-ST-elevation acute coronary syndrome based on the RITA 3 trial. Heart 94: 717-723 [Abstract] [Full Text]  
• Vrints, C. J. M. (2008). Acute coronary syndrome in the elderly. Eur Heart J 29: 1213-1214 [Full Text]  
• American College of Cardiology/American Heart Asso, , 2007 Writing Group to Review New Evidence and Upda, , King, S. B. III, Smith, S. C. Jr, Hirshfeld, J. W. Jr, Jacobs, A. K., Morrison, D. A., Williams, D. O. (2008). 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention. J Am Coll Cardiol 51: 172-209 [Full Text]  
• King, S. B. III, Smith, S. C. Jr, Hirshfeld, J. W. Jr, Jacobs, A. K., Morrison, D. A., Williams, D. O., 2005 WRITING COMMITTEE MEMBERS, , Smith, S. C. Jr, Feldman, T. E., Hirshfeld, J. W. Jr, Jacobs, A. K., Kern, M. J., King, S. B. III, Morrison, D. A., O'Neill, W. W., Schaff, H. V., Whitlow, P. L., Williams, D. O., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Buller, C. E., Creager, M. A., Ettinger, S. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Page, R. L., Riegel, B., Tarkington, L. G., Yancy, C. W. (2008). 2007 Focused Update of the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines: 2007 Writing Group to Review New Evidence and Update the ACC/AHA/SCAI 2005 Guideline Update for Percutaneous Coronary Intervention, Writing on Behalf of the 2005 Writing Committee. Circulation 117: 261-295 [Full Text]  
• Tricoci, P., Lokhnygina, Y., Berdan, L. G., Steinhubl, S. R., Gulba, D. C., White, H. D., Kleiman, N. S., Aylward, P. E., Langer, A., Califf, R. M., Ferguson, J. J., Antman, E. M., Newby, L. K., Harrington, R. A., Goodman, S. G., Mahaffey, K. W. (2007). Time to Coronary Angiography and Outcomes Among Patients With High-Risk Non ST-Segment Elevation Acute Coronary Syndromes: Results From the SYNERGY Trial. Circulation 116: 2669-2677 [Abstract] [Full Text]  
• Alfredsson, J., Stenestrand, U., Wallentin, L., Swahn, E. (2007). Gender differences in management and outcome in non-ST-elevation acute coronary syndrome. Heart 93: 1357-1362 [Abstract] [Full Text]  
• Wollert, K. C., Kempf, T., Lagerqvist, B., Lindahl, B., Olofsson, S., Allhoff, T., Peter, T., Siegbahn, A., Venge, P., Drexler, H., Wallentin, L. (2007). Growth Differentiation Factor 15 for Risk Stratification and Selection of an Invasive Treatment Strategy in Non ST-Elevation Acute Coronary Syndrome. Circulation 116: 1540-1548 [Abstract] [Full Text]  
• Mark, D. B (2007). Percutaneous coronary revascularisation: is it ever worth what it costs?. Heart 93: 1161-1163 [Full Text]  
• Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E. Jr, Chavey, W. E. II, Fesmire, F. M., Hochman, J. S., Levin, T. N., Lincoff, A. M., Peterson, E. D., Theroux, P., Wenger, N. K., Wright, R. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B. (2007). 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. J Am Coll Cardiol 50: e1-e157 [Full Text]  
• Anderson, J. L., Adams, C. D., Antman, E. M., Bridges, C. R., Califf, R. M., Casey, D. E. Jr, Chavey, W. E. II, Fesmire, F. M., Hochman, J. S., Levin, T. N., Lincoff, A. M., Peterson, E. D., Theroux, P., Wenger, N. K., Wright, R. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Halperin, J. L., Hunt, S. A., Krumholz, H. M., Kushner, F. G., Lytle, B. W., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B. (2007). ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction Executive Summary: 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. J Am Coll Cardiol 50: 652-726 [Full Text]  
• Rosendorff, C., Black, H. R., Cannon, C. P., Gersh, B. J., Gore, J., Izzo, J. L. Jr, Kaplan, N. M., O'Connor, C. M., O'Gara, P. T., Oparil, S. (2007). REPRINT Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease: A Scientific Statement From the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Hypertension 50: e28-e55 [Full Text]  
• Authors/Task Force Members, , Bassand, J.-P., Hamm, C. W., Ardissino, D., Boersma, E., Budaj, A., Fernandez-Aviles, F., Fox, K. A.A., Hasdai, D., Ohman, E. M., Wallentin, L., Wijns, W., ESC Committee for Practice Guidelines (CPG), , Vahanian, A., Camm, J., De Caterina, R., Dean, V., Dickstein, K., Filippatos, G., Kristensen, S. D., Widimsky, P., McGregor, K., Sechtem, U., Tendera, M., Hellemans, I., Gomez, J. L. Z., Silber, S., Funck-Brentano, C., Document Reviewers, , Kristensen, S. D., Andreotti, F., Benzer, W., Bertrand, M., Betriu, A., De Caterina, R., DeSutter, J., Falk, V., Ortiz, A. F., Gitt, A., Hasin, Y., Huber, K., Kornowski, R., Lopez-Sendon, J., Morais, J., Nordrehaug, J. E., Silber, S., Steg, P. G., Thygesen, K., Tubaro, M., Turpie, A. G.G., Verheugt, F., Windecker, S. (2007). Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes: The Task Force for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndromes of the European Society of Cardiology. Eur Heart J 28: 1598-1660 [Full Text]  
• Peters, R. J G, Mehta, S., Yusuf, S. (2007). Acute coronary syndromes without ST segment elevation. BMJ 334: 1265-1269 [Full Text]  
• Mahmarian, J. J., Pratt, C. M. (2007). Reply. J Am Coll Cardiol 49: 2227-2228 [Full Text]  
• Rosendorff, C., Black, H. R., Cannon, C. P., Gersh, B. J., Gore, J., Izzo, J. L. Jr, Kaplan, N. M., O'Connor, C. M., O'Gara, P. T., Oparil, S. (2007). Treatment of Hypertension in the Prevention and Management of Ischemic Heart Disease: A Scientific Statement From the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention. Circulation 115: 2761-2788 [Full Text]  
• Alexander, K. P., Newby, L. K., Cannon, C. P., Armstrong, P. W., Gibler, W. B., Rich, M. W., Van de Werf, F., White, H. D., Weaver, W. D., Naylor, M. D., Gore, J. M., Krumholz, H. M., Ohman, E. M. (2007). Acute Coronary Care in the Elderly, Part I: Non-ST-Segment-Elevation Acute Coronary Syndromes: A Scientific Statement for Healthcare Professionals From the American Heart Association Council on Clinical Cardiology: In Collaboration With the Society of Geriatric Cardiology. Circulation 115: 2549-2569 [Abstract] [Full Text]  
• Newby, L. K., Peterson, E. D. (2007). Does Ranolazine Have a Place in the Treatment of Acute Coronary Syndromes?. JAMA 297: 1823-1825 [Full Text]  
• Boden, W. E., O'Rourke, R. A., Teo, K. K., Hartigan, P. M., Maron, D. J., Kostuk, W. J., Knudtson, M., Dada, M., Casperson, P., Harris, C. L., Chaitman, B. R., Shaw, L., Gosselin, G., Nawaz, S., Title, L. M., Gau, G., Blaustein, A. S., Booth, D. C., Bates, E. R., Spertus, J. A., Berman, D. S., Mancini, G.B. J., Weintraub, W. S., the COURAGE Trial Research Group, (2007). Optimal Medical Therapy with or without PCI for Stable Coronary Disease. NEJM 356: 1503-1516 [Abstract] [Full Text]  
• Hollenbeak, C. S., Fitzgibbons, J. P., Rossi, M., Morris, D. L., Stillman, P. (2007). The Impact of Percutaneous Coronary Interventions on Outcomes for Acute Myocardial Infarction in Pennsylvania. American Journal of Medical Quality 22: 85-94 [Abstract]  
• Held, C., Tornvall, P., Stenestrand, U. (2007). Effects of revascularization within 14 days of hospital admission due to acute coronary syndrome on 1-year mortality in patients with previous coronary artery bypass graft surgery. Eur Heart J 28: 316-325 [Abstract] [Full Text]  
• Neumann, F.-J., Buttner, H. J. (2007). Underuse of revascularisation in acute coronary syndromes. Heart 93: 147-148 [Abstract] [Full Text]  
• Neumann, F.-J., Kastrati, A., Schwarzer, G. (2007). New aspects in the treatment of acute coronary syndromes without ST-elevation: ICTUS and ISAR-COOL in perspective. Eur Heart J Suppl 9: A4-A10 [Abstract] [Full Text]  
• Fox, K A A, Anderson, F A Jr, Dabbous, O H, Steg, P G, Lopez-Sendon, J, Van de Werf, F, Budaj, A, Gurfinkel, E P, Goodman, S G, Brieger, D, on behalf of the GRACE investigators, (2007). 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 93: 177-182 [Abstract] [Full Text]  
• Mahmarian, J. J., Dakik, H. A., Filipchuk, N. G., Shaw, L. J., Iskander, S. S., Ruddy, T. D., Keng, F., Henzlova, M. J., Allam, A., Moye, L. A., Pratt, C. M., for the INSPIRE Investigators, (2006). An Initial Strategy of Intensive Medical Therapy Is Comparable to That of Coronary Revascularization for Suppression of Scintigraphic Ischemia in High-Risk But Stable Survivors of Acute Myocardial Infarction. J Am Coll Cardiol 48: 2458-2467 [Abstract] [Full Text]  
• Mahmarian, J. J., Shaw, L. J., Filipchuk, N. G., Dakik, H. A., Iskander, S. S., Ruddy, T. D., Henzlova, M. J., Keng, F., Allam, A., Moye, L. A., Pratt, C. M., for the INSPIRE Investigators, (2006). A Multinational Study to Establish the Value of Early Adenosine Technetium-99m Sestamibi Myocardial Perfusion Imaging in Identifying a Low-Risk Group for Early Hospital Discharge After Acute Myocardial Infarction. J Am Coll Cardiol 48: 2448-2457 [Abstract] [Full Text]  
• Dzau, V. J., Antman, E. M., Black, H. R., Hayes, D. L., Manson, J. E., Plutzky, J., Popma, J. J., Stevenson, W. (2006). The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part II: Clinical Trial Evidence (Acute Coronary Syndromes Through Renal Disease) and Future Directions. Circulation 114: 2871-2891 [Full Text]  
• Van Brabandt, H., Camberlin, C., Vrijens, F., Parmentier, Y., Ramaekers, D., Bonneux, L. (2006). More is not better in the early care of acute myocardial infarction: a prospective cohort analysis on administrative databases. Eur Heart J 27: 2649-2654 [Abstract] [Full Text]  
• Bavry, A. A., Kumbhani, D. J., Rassi, A. N., Bhatt, D. L., Askari, A. T. (2006). Benefit of Early Invasive Therapy in Acute Coronary Syndromes: A Meta-Analysis of Contemporary Randomized Clinical Trials. J Am Coll Cardiol 48: 1319-1325 [Abstract] [Full Text]  
• Poole-Wilson, P A, Pocock, S J, Fox, K A A, Henderson, R A, Wheatley, D J, Chamberlain, D A, Shaw, T R D, Clayton, T C, for the Randomised Intervention Trial of unstable, (2006). Interventional versus conservative treatment in acute non-ST elevation coronary syndrome: time course of patient management and disease events over one year in the RITA 3 trial. Heart 92: 1473-1479 [Abstract] [Full Text]  
• de Winter, R. J. (2006). Commentary on Clinical Guidelines and Practice: In Search of the Truth by Dean J. Kereiakes and Elliott M. Antman. J Am Coll Cardiol 48: 1136-1138 [Abstract] [Full Text]  
• Kereiakes, D. J., Antman, E. M. (2006). Clinical Guidelines and Practice: In Search of the Truth. J Am Coll Cardiol 48: 1129-1135 [Abstract] [Full Text]  
• Westerhout, C. M., Fu, Y., Lauer, M. S., James, S., Armstrong, P. W., Al-Hattab, E., Califf, R. M., Simoons, M. L., Wallentin, L., Boersma, E., on behalf of the GUSTO-IV ACS Trial Investigators, (2006). Short- and Long-Term Risk Stratification in Acute Coronary Syndromes: The Added Value of Quantitative ST-Segment Depression and Multiple Biomarkers. J Am Coll Cardiol 48: 939-947 [Abstract] [Full Text]  
• Giugliano, R. P., Braunwald, E. (2006). The Year in Non-ST-Segment Elevation Acute Coronary Syndromes. J Am Coll Cardiol 48: 386-395 [Full Text]  
• Alexander, K. P., Newby, L. K., Bhapkar, M. V., White, H. D., Hochman, J. S., Pfisterer, M. E., Moliterno, D. J., Peterson, E. D., Van de Werf, F., Armstrong, P. W., Califf, R. M., for the SYMPHONY and 2nd SYMPHONY Investigators, (2006). International variation in invasive care of the elderly with acute coronary syndromes. Eur Heart J 27: 1558-1564 [Abstract] [Full Text]  
• Rasoul, S., Ottervanger, J. P., de Boer, M.-J., Miedema, K., Hoorntje, J. C.A., Gosselink, M., Zijlstra, F., Suryapranata, H., Dambrink, J.-H. E., van 't Hof, A. W.J. (2006). A comparison of dual vs. triple antiplatelet therapy in patients with non-ST-segment elevation acute coronary syndrome: results of the ELISA-2 trial. Eur Heart J 27: 1401-1407 [Abstract] [Full Text]  
• Dixon, S. R., Grines, C. L., O'Neill, W. W. (2006). The Year in Interventional Cardiology. J Am Coll Cardiol 47: 1689-1706 [Full Text]  
• (2006). ADDITIONAL ARTICLES ABSTRACTED IN ACP JOURNAL CLUB. Evid. Based Med. 11: 62-62 [Full Text]  
• Skinner, J. S., Staiger, D. O., Fisher, E. S. (2006). Is Technological Change In Medicine Always Worth It? The Case Of Acute Myocardial Infarction. Health Aff (Millwood) 25: w34-w47 [Abstract] [Full Text]  
• Chiara, A. D., Fresco, C., Savonitto, S., Greco, C., Lucci, D., Gonzini, L., Mafrici, A., Ottani, F., Bolognese, L., De Servi, S., Boccanelli, A., Maggioni, A. P., Chiarella, F., on behalf of the BLITZ-2 Investigators, (2006). Epidemiology of non-ST elevation acute coronary syndromes in the Italian cardiology network: the BLITZ-2 study. Eur Heart J 27: 393-405 [Abstract] [Full Text]  
• (2005). Invasive vs. Conservative Management of NSTEACS. Journal Watch Cardiology 2005: 7-7 [Full Text]  
• Tarantini, G., Ramondo, A., Iliceto, S., Newby, D. E., Fox, K. A., Ionescu, A., Garg, A., Spaulding, C., Varenne, O., Weber, S., Costantino, G., Raggi, F., Montano, N., Garcia-Pavia, P., Aguiar-Souto, P., Silva-Melchor, L., de Winter, R. J., Windhausen, F., Tijssen, J. G.P., Boden, W. E. (2005). Management of Acute Coronary Syndromes. NEJM 353: 2714-2718 [Full Text]  
• Malik, I. (2005). JournalScan. Heart 91: 1631-1632 [Full Text]  
• (2005). All Non-ST-Segment-Elevation Acute Coronary Syndromes to the Cath Lab? Maybe Not. JWatch Emergency Med. 2005: 2-2 [Full Text]  
• (2005). Invasive vs. Conservative Management of NSTEACS. Journal Watch Cardiology 2005: 1-1 [Full Text]  
• (2005). Routine vs. Selective Invasive Management for Acute Coronary Syndromes. JWatch General 2005: 1-1 [Full Text]  
• Tonks, A. (2005). What's new in the other general journals. BMJ 331: 657-658 [Full Text]  
• Boden, W. E. (2005). Acute Coronary Syndromes without ST-Segment Elevation -- What Is the Role of Early Intervention?. NEJM 353: 1159-1161 [Full Text]