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

Volume 338:1785-1792 June 18, 1998 Number 25 Next

Abstract PDF Editorial by Lange, R. A. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article Related Article by Malawer, M. M. PubMed Citation

ABSTRACT

Background Non–Q-wave myocardial infarction is usually managed according to an "invasive" strategy (i.e., one of routine coronary angiography followed by myocardial revascularization).

Methods We randomly assigned 920 patients to either "invasive" management (462 patients) or "conservative" management, defined as medical therapy and noninvasive testing, with subsequent invasive management if indicated by the development of spontaneous or inducible ischemia (458 patients), within 72 hours of the onset of a non–Q-wave infarction. Death or nonfatal infarction made up the combined primary end point.

Results During an average follow-up of 23 months, 152 events (80 deaths and 72 nonfatal infarctions) occurred in 138 patients who had been randomly assigned to the invasive strategy, and 139 events (59 deaths and 80 nonfatal infarctions) in 123 patients assigned to the conservative strategy (P=0.35). Patients assigned to the invasive strategy had worse clinical outcomes during the first year of follow-up. The number of patients with one of the components of the primary end point (death or nonfatal myocardial infarction) and the number who died were significantly higher in the invasive-strategy group at hospital discharge (36 vs. 15 patients, P=0.004, for the primary end point; 21 vs. 6, P=0.007, for death), at one month (48 vs. 26, P=0.012; 23 vs. 9, P=0.021), and at one year (111 vs. 85, P=0.05; 58 vs. 36, P=0.025). Overall mortality during follow-up did not differ significantly between patients assigned to the conservative-strategy group and those assigned to the invasive-strategy group (hazard ratio, 0.72; 95 percent confidence interval, 0.51 to 1.01).

Conclusions Most patients with non–Q-wave myocardial infarction do not benefit from routine, early invasive management consisting of coronary angiography and revascularization. A conservative, ischemia-guided initial approach is both safe and effective.

Although the 1987 American College of Cardiology–American Heart Association guidelines for coronary arteriography¹⁷ recommended routine coronary angiography for all patients after non–Q-wave infarction, newer guidelines no longer endorse this approach to treatment.^18,19 Nevertheless, early invasive management is still widely practiced. Furthermore, several recent studies of patients with acute coronary syndromes have shown either no effect or an adverse effect when routine coronary angiography is followed by early myocardial revascularization.^20,21,22,23 Thus, despite the paucity of supporting data, many physicians assume that an "invasive" strategy (one characterized by routine coronary angiography followed by revascularization, if feasible) is superior to a "conservative" strategy (consisting of medical therapy, noninvasive testing, and subsequent invasive procedures if indicated by the development of spontaneous or inducible ischemia — i.e., an ischemia-guided approach) in terms of improving clinical outcomes.

To test this hypothesis, we initiated a multicenter, randomized, controlled trial to compare an invasive with a conservative strategy in patients with acute non–Q-wave myocardial infarction; the combined primary end point was death from any cause or recurrent nonfatal infarction during a minimum of 12 months of follow-up.

Methods

Study Organization

The Veterans Affairs Non–Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial began enrollment on April 14, 1993, after the institutional review boards at 15 participating centers had approved the protocol. Two study sites were dropped within six months because of poor enrollment, and an additional two sites were added later. Thus, 15 sites completed the study. This report includes data from all 17 sites. A data-monitoring board independently reviewed the interim results at regular intervals.

Selection of Patients

Details of the trial design have been published elsewhere.²⁴ Eligible patients had to have evolving acute myocardial infarction, a level of creatine kinase MB (CK-MB) isoenzymes that was more than 1.5 times the upper limit of normal for the hospital, and no new abnormal Q waves (or R waves) on serial electrocardiograms. Patients were excluded if they had serious coexisting conditions, ischemic complications that placed them at very high risk while in the coronary care unit (persistent or recurrent ischemia at rest despite intensive medical therapy or severe heart failure that persisted despite treatment with intravenous diuretics, vasodilators, or both). These were conditions that were deemed to pose clinical or ethical problems for the inclusion of patients in a randomized trial.²⁴

The electrocardiographic analysis followed the Atlanta code,²⁵ with serial tracings obtained at multiple times after the onset of infarction. At least one electrocardiogram was obtained 48 hours after admission in order to rule out the late development of Q waves.²⁶ Electrocardiographically, the study patients had neither new, abnormal Q waves (i.e., Q waves lasting 0.04 second in two contiguous leads within a group of leads) nor R waves (more than 0.04 second in lead V₁ and an R:S ratio greater than 1 in lead V₂); we have previously demonstrated that these criteria reliably exclude evolving posterior infarction.^26,27

Randomization Procedure

The study patients gave informed, written consent and were randomly assigned to a study group within 24 to 72 hours after the onset of symptoms according to the adaptive-allocation procedure,²⁸ which maximized the probability of balance between the treatment groups within the medical centers and with respect to each of five variables used for stratification: age, previous myocardial infarction, use of thrombolytic therapy, anterior location of the infarct, and ST-segment depression on the electrocardiogram obtained at entry.

Testing and Treatment

Patients assigned to the early invasive strategy underwent coronary angiography as the initial diagnostic test soon after randomization. Thereafter, the management guidelines of the Thrombolysis in Myocardial Infarction trial (TIMI IIIB) for revascularization were followed.²⁰ In patients with clinically significant single-vessel coronary artery disease, balloon angioplasty or, rarely, directional atherectomy was considered, whereas bypass surgery was recommended for patients with multivessel disease. In contrast to the TIMI IIIB guidelines, however, our protocol did not require early myocardial revascularization; investigators at each study site were allowed to decide whether to perform only revascularization of a culprit stenosis, perform complete revascularization, or continue medical therapy.

Patients assigned to the early conservative strategy underwent radionuclide ventriculography to assess left ventricular function as the initial noninvasive test; this was followed before discharge by a symptom-limited treadmill exercise test (according to the standard Bruce protocol) with planar thallium scintigraphy or thallium scintigraphy with single-photon-emission computed tomography. Patients who were unable to exercise to a level of at least 5 metabolic equivalents (MET) received intravenous dipyridamole (0.56 mg per kilogram of body weight) and then underwent perfusion scintigraphy.

Coronary angiography with or without revascularization was performed in patients randomly assigned to the conservative strategy only if one or more of the following three criteria were met: the patient had recurrent postinfarction angina with ischemic electrocardiographic changes; the patient had ST-segment depression of at least 2 mm on an electrocardiogram recorded during peak exercise; or there were redistribution defects in two or more different vascular regions on thallium scintigraphy, or one redistribution defect with increased uptake of thallium by the lung. Investigators at the study site decided whether to perform myocardial revascularization in patients who had objective evidence of ischemia.

Patients in both groups received enteric-coated aspirin (325 mg per day) and long-acting diltiazem (Cardizem, Hoechst Marion Roussel, Kansas City, Mo.; 180 to 300 mg per day), on the basis of the reported benefit of this combination for secondary prevention.^{5,7,29,30,31,32} In addition, patients could receive any other standard medical therapy during hospitalization, including nitroglycerin, angiotensin-converting–enzyme inhibitors, beta-blockers, dose-adjusted intravenous heparin, and if clinically indicated, thrombolytic therapy.²⁴

Follow-Up

Enrollment ended on December 31, 1995. Patients were seen one month after discharge and at three-month intervals thereafter until the trial ended on December 31, 1996.

End Points

The primary end point of the trial was death or nonfatal myocardial infarction. An independent, three-member end-points committee, whose members were unaware of the treatment assignments, reviewed and adjudicated all suspected primary end points. We also analyzed overall mortality and major procedural complications after coronary angiography or myocardial revascularization.

Statistical Analysis

Sample size was calculated for an equivalence study on the basis of binomial proportions.³³ Our null hypothesis was that 20 percent of each group would reach a primary end point during 12 months of follow-up,^30,34 and we postulated that the null hypothesis of equivalence would be rejected if the difference between the groups exceeded 7.5 percent, with a two-sided significance level of 0.05 and 80 percent power.²⁴ The study chairman and executive committee were masked with respect to the results throughout the trial. Formal interim analyses for efficacy were conducted by the data-monitoring board, using accepted methods.^24,35,36

Continuous data are presented as means ±SD. Odds ratios and 95 percent confidence intervals were used to compare the strategies with respect to major clinical outcomes. Survival curves were used to characterize the timing of the primary end point during follow-up, according to the method of Kaplan and Meier.³⁷ The Cox proportional-hazards regression model³⁸ was used to adjust for covariates in the analysis of the interaction between the strategy assignment and the five prespecified covariates. All tests of significance were two-tailed, and the strategies were compared according to the intention-to-treat principle.

Results

Characteristics of the Study Population

Among 2738 patients with non–Q-wave myocardial infarction confirmed by measurement of CK-MB isoenzymes who were identified at screening, 920 patients (34 percent) were randomly assigned to treatment groups: 462 to the invasive-strategy group and 458 to the conservative-strategy group. A total of 247 patients (9 percent) were excluded because of very-high-risk ischemic complications during the first 48 hours after the onset of infarction.²⁴ The base-line characteristics of the subjects are shown in Table 1. Ninety-seven percent of the study population were men. Eight percent of the patients were older than 75 years, and 40 percent were older than 65. Vital status at one year was verified for 913 patients (the other 7 patients were assumed to be alive after searches of death registries had negative results); follow-up at one year was more than 99 percent complete.

View this table: [in this window] [in a new window]   Table 1. Base-Line Characteristics of the Patients Randomly Assigned to the Invasive and Conservative Strategies.

 
End-Point Analyses

A total of 152 cardiac events (80 deaths and 72 nonfatal infarctions) occurred in 138 patients in the invasive-strategy group, as did 139 cardiac events (59 deaths and 80 nonfatal infarctions) in 123 patients in the conservative-strategy group (P=0.35) during an average of 23 months of follow-up (range, 12 to 44). As shown in Figure 1, the cumulative rates of death or nonfatal infarction in the groups did not differ significantly during long-term follow-up (hazard ratio for the conservative-strategy group as compared with the invasive-strategy group, 0.87; 95 percent confidence interval, 0.68 to 1.10), although there were striking differences between the groups in early clinical outcomes (i.e., clinical outcomes in the first 12 months). The frequency of death or nonfatal myocardial infarction was higher in the invasive-strategy group than in the conservative-strategy group before hospital discharge (36 vs. 15 events, P=0.004), at one month (48 vs. 26 events, P=0.012), and at one year (111 vs. 85 events, P= 0.05). The same was true for the rate of death (21 vs. 6 deaths, P=0.007; 23 vs. 9, P=0.21; and 58 vs. 36, P=0.025, respectively).

View larger version (4K): [in this window] [in a new window]   Figure 1. Kaplan–Meier Analysis of the Probability of Event-free Survival According to Strategy Group during 12 to 44 Months of Follow-up. The events included in this analysis were death and nonfatal myocardial infarction (which together made up the primary end point). The Cox proportional-hazards ratio for the conservative as compared with the invasive strategy was 0.87 (95 percent confidence interval, 0.68 to 1.10).

 
During long-term follow-up, cumulative mortality from all causes did not differ significantly between the patients assigned to the conservative strategy and those assigned to the invasive strategy (hazard ratio, 0.72; 95 percent confidence interval, 0.51 to 1.01) (Figure 2). Even among the 805 patients who did not receive thrombolytic therapy, there were more deaths in the invasive-strategy group (69 deaths) than in the conservative-strategy group (58). There were no significant differences between the groups in the incidence of nonfatal myocardial infarction during follow-up. Finally, there was remarkable consistency among the study sites; patients in the invasive-strategy group fared worse than those in the conservative-strategy group at 11 of 15 centers (73 percent).

View larger version (3K): [in this window] [in a new window]   Figure 2. Kaplan-Meier Analysis of the Probability of Survival According to Strategy Group during 12 to 44 Months of Follow-up. Death from any cause was included in this analysis. The Cox proportional-hazards ratio for the conservative as compared with the invasive strategy was 0.72 (95 percent confidence interval, 0.51 to 1.01).

 
Clinical Outcomes According to Treatment Strategy and Myocardial Revascularization

The clinical outcomes of all 920 patients are summarized in Table 2. Among the 462 patients assigned to the invasive strategy, 442 (96 percent) underwent coronary angiography (435 before hospital discharge and 439 by 30 days after the onset of symptoms). Among the 458 patients in the conservative-strategy group, only 24 percent (110 patients) underwent coronary angiography before discharge, and 29 percent (133 patients) by 30 days. Of the 110 patients who underwent catheterization before discharge, 45 percent had recurrent angina with ischemic electrocardiographic changes, 20 percent had ST-segment deviation of at least 2 mm during exercise testing, and 47 percent had one or more reversible perfusion defects during thallium scintigraphy.

View this table: [in this window] [in a new window]   Table 2. Clinical Outcomes of Patients Who Underwent Coronary Angiography with Revascularization, Coronary Angiography without Revascularization, or No Coronary Angiography.

 
The prevalence of multivessel coronary artery disease was high; 74 percent of patients in the invasive-strategy group and 80 percent of those in the conservative-strategy group had substantial left-main-stem stenosis, reduction of 50 percent or more of the luminal diameter in two or more major epicardial coronary arteries, or both.

A total of 204 patients (44 percent) underwent myocardial revascularization in the invasive-strategy group (95 had coronary-artery bypass graft surgery [CABG], 98 underwent percutaneous transluminal coronary angioplasty [PTCA], and 11 had both procedures), as did 152 (33 percent) in the conservative-strategy group (87 underwent CABG, 55 PTCA, and 10 both procedures) (Table 2 and Table 3). Revascularization was performed earlier after randomization and within a narrower interval in the invasive-strategy group. Mortality 30 days after PTCA was 0 (0 of 98 patients) in the invasive-strategy group and 3.6 percent (2 of 55) in the conservative-strategy group — for a composite rate of 1.3 percent (Table 3). The 30-day death rate among patients who underwent only CABG was 7.7 percent (14 of 182 patients); 11 deaths occurred in the invasive-strategy group and 3 in the conservative-strategy group. Among the 21 patients who underwent both CABG and PTCA, only one death (4.8 percent) occurred (in a patient assigned to the conservative strategy). Overall, the death rate 30 days after revascularization was 4.8 percent (17 of 356 patients).

View this table: [in this window] [in a new window]   Table 3. Mortality 30 Days after Revascularization in the Two Treatment-Strategy Groups.

 
Of the 236 patients assigned to the conservative strategy who did not undergo angiography (52 percent), only 1.3 percent had had a nonfatal infarction or died by 30 days, and 11 percent by 1 year. The mortality was only 1 percent at 30 days and 6 percent at 1 year. Finally, the duration of hospitalization was significantly longer in the invasive-strategy group than in the conservative-strategy group (9.5 vs. 8.2 days, P=0.024).

Therapy with Drugs and Devices

At hospital discharge (a mean of 8.8 days after the onset of symptoms), 89 percent of patients were receiving aspirin, 52 percent a beta-blocker, and 55 percent a calcium-channel antagonist (diltiazem in 42 percent and another drug in 13 percent). There were no significant differences between the groups in use of medications. Certain newer treatment methods emerged during the course of the trial and were approved for clinical use after enrollment began; among them were stenting (in mid-1994) and platelet glycoprotein IIb/IIIa receptor antagonists (in 1995). Ticlopidine was not used routinely after PTCA.

Interaction Analysis

The lengths of time to death and to a cardiac event (death or nonfatal myocardial infarction) were compared for each of the five prespecified variables used in stratification in order to determine whether the main results were consistent among subgroups (Figure 3). For death, there was moderately strong statistical evidence of benefit in the conservative-strategy group for 4 of 10 subgroups (patients who underwent thrombolysis, those with no prior infarction, those with no ST-segment depression, and those who were 60 or older). In no subgroup was the invasive strategy associated with a better outcome. For the combined primary end point, neither strategy conferred a statistically reliable advantage in any subgroup.

View larger version (6K): [in this window] [in a new window]   Figure 3. Hazard Ratios for Death in the Two Strategy Groups with Stratification According to Five Prespecified Variables. We conducted this interaction analysis for time to death in subgroups, using the Cox proportional-hazards model, in order to determine whether the main results were consistent among subgroups. Hazard ratios are shown with 95 percent confidence intervals. Hazard ratios that are less than 1.0 with confidence intervals that do not cross the unity boundary favor conservative management, and ratios above 1.0 favor invasive management. MI denotes myocardial infarction.

 
Discussion

In this large, prospective, randomized trial of management of non–Q-wave myocardial infarction, we observed a substantial 28 percent rate of cardiac events during follow-up of 12 to 44 months, but no early or late clinical benefit with routine invasive management. Although the cumulative rate of death or recurrent infarction did not differ significantly between the two study groups, the rates of death or nonfatal myocardial infarction and of death were significantly higher during the first year of follow-up among patients randomly assigned to the invasive strategy. Both at hospital discharge and at 30 days, the rate of cardiac events and deaths among patients in the invasive-strategy group was increased by a factor of two to three, as compared with the rate in the conservative-strategy group. Moreover, overall mortality was significantly lower throughout the entire first year after infarction among patients assigned to the conservative strategy. The mortality curves for each strategy tended to converge by the end of follow-up (Figure 2), a pattern that is not surprising in a population of patients with non–Q-wave myocardial infarction who were followed for up to 44 months.

For clinical and ethical reasons, we excluded a subgroup of patients with very-high-risk ischemic complications for whom an early invasive approach was clinically warranted; only 9 percent of all eligible patients with non–Q-wave infarction had such complications, however. Instead, our main goal was to assess the role of routine, early invasive management in the remaining patients with non–Q-wave infarction, more than 90 percent of the total, who were clinically stable at the time of transfer from the coronary care unit.

No subgroup of patients with non–Q-wave infarction appeared to benefit from an early invasive approach to treatment. Patients with anterior infarction, ST-segment depression on the electrocardiogram at entry, a reduced ejection fraction, or a previous infarction did not fare better with routine invasive management than with conservative treatment. Exclusion of the 115 patients who received early thrombolytic therapy did not change our overall findings.

Two other studies are relevant to our findings. In TIMI IIIB, there were no significant differences in the rates of death or recurrent infarction at six weeks among 1473 patients with acute coronary syndromes or in the subgroup of 476 patients with non–Q-wave infarction who were randomly assigned to an invasive strategy (18 events) or to a conservative strategy (22 events).²⁰ In TIMI IIIB, 64 percent of patients in the conservative-strategy group underwent coronary angiography within 6 weeks of randomization (90 percent of them within 10 days). In the current VANQWISH Trial, only 29 percent of patients in the conservative-strategy group subsequently underwent catheterization because they had objective signs of ischemia within 30 days.

The findings of the Danish Multicenter Randomized Study of Invasive versus Conservative Treatment in Patients with Inducible Ischemia after Thrombolysis in Acute Myocardial Infarction (DANAMI)³⁹ are indirectly related to our findings in the VANQWISH Trial. In DANAMI, only patients with first infarctions treated initially with thrombolytic therapy were included; 25 percent were classified as having non–Q-wave infarctions.³⁹ In VANQWISH, the median lengths of time from randomization to coronary angiography and revascularization in the invasive-therapy group were 2 days and 8 days, respectively, whereas in DANAMI this interval ranged from 2 to 10 weeks. The incidence of subsequent reinfarction and unstable angina was lower among patients in DANAMI who were assigned to the invasive strategy, but there was no significant difference in mortality.³⁹ The combined rate of death or reinfarction in DANAMI during a median follow-up of 2.4 years was 12 percent, whereas in the VANQWISH Trial it was 28 percent. Thus, as compared with the patient groups in both TIMI IIIB²⁰ and DANAMI,³⁹ our patients were at higher risk.²⁴ There was no clear benefit to routine early invasive management in terms of reducing mortality in any of the trials.

In the VANQWISH Trial, the 30-day death rate after CABG (7.7 percent) occurred in patients at moderately high risk among whom the event rate probably reflects the severity of their illness. Our findings are consistent with other reports that emphasize the fact that preoperative variables that identify patients as being at high risk (such as recent infarction) are associated with higher short-term mortality after CABG.^40,41,42,43 A recent study of 5517 patients who underwent CABG in 1993 showed that in-hospital mortality was highest among patients who underwent surgery within seven days of myocardial infarction (13 percent); who had previously undergone CABG (11 percent); who had peripheral or cerebral vascular disease (9 percent); who were 65 years of age or older (4 percent); or who had diabetes (3 percent).⁴⁰ These characteristics were common among our patients with non–Q-wave infarction.²⁴

Several implications of our findings are noteworthy. First, the very low 30-day death rate after PTCA (1.3 percent) — even without stenting — was virtually identical to that observed at 30 days with conservative ischemia-guided management and no coronary angiography (1 percent) (Table 2). Second, early conservative management did not imply only watchful waiting; it embodied medical therapy, careful noninvasive testing, and coronary angiography, with or without myocardial revascularization, as indicated when ischemia recurred. Third, we found no evidence that using a routine strategy of early invasive treatment resulted in more expeditious management or shorter hospitalizations. Finally, routine coronary angiography in otherwise stable patients often leads to unnecessary revascularization procedures such as PTCA, the rate of which rose almost 6000 percent between 1980 and 1992.⁴⁴

Our study has limitations. First, the study was not designed to compare myocardial revascularization with intensive medical therapy in survivors of acute non–Q-wave myocardial infarction. Considering the low rate of cardiac events among patients treated with conservative management, it seems unlikely that more aggressive intervention would have resulted in a different outcome. Nevertheless, clinical outcomes in the invasive-strategy group could have been different if a larger percentage of patients had undergone revascularization. Second, the very low percentage of female patients enrolled limits the generalizability of the overall findings to women. Third, the VANQWISH Trial was conducted before coronary stents or platelet glycoprotein IIb/IIIa receptor antagonists were widely available. Although it is possible that clinical outcomes might have been different in the invasive-strategy group if we had used stents, novel antiplatelet agents, or both, the long-term effects of such therapies in this population remain uncertain.

In summary, in this predominantly male population of moderate-to-high-risk patients with non–Q-wave myocardial infarction, we found no evidence that clinical outcomes were improved by a routine strategy of early invasive treatment; in fact, we observed substantial risk overall with this approach during the first year after infarction. By contrast, patients who were treated initially according to a conservative strategy had significantly lower mortality at hospital discharge, at one month, and at one year. These findings indicate that most patients with non–Q-wave myocardial infarction are not likely to benefit from routine early invasive treatment. A conservative initial strategy based on an ischemia-guided approach to management after infarction is both safe and effective.

Supported by a research grant from the Department of Veterans Affairs Cooperative Studies Program and by an unrestricted research grant from Hoechst Marion Roussel.

^* The study sites, investigators, and study personnel participating in the VANQWISH Trial are listed in the Appendix.

Source Information

From the Veterans Affairs Medical Center and the State University of New York Health Science Center, Syracuse (W.E.B.); the Veterans Affairs Medical Center, San Antonio, Tex. (R.A.O.); the Veterans Affairs Medical Center, Albuquerque, N.M. (M.H.C.); the Veterans Affairs Medical Center, Houston (A.S.B.); the Veterans Affairs Medical Center, Fresno, Calif. (P.C.D.); the James A. Haley Veterans Affairs Medical Center, Tampa, Fla. (R.G.Z); the Veterans Affairs Medical Center, Cincinnati (L.F. W.); Jewish Hospital, Washington University School of Medicine, St. Louis (R.E.K.); the Veterans Affairs Medical Center, Gainesville, Fla. (C.J.P.); the Jerry L. Pettis Veterans Affairs Medical Center, Loma Linda, Calif. (D.R.F.); and the Department of Veterans Affairs Cooperative Studies Program Coordinating Center, Palo Alto, Calif. (B.K.C., P. W.L.).

Address reprint requests to Dr. Boden at the Medical Service, Veterans Affairs Healthcare Network of Upstate New York, 800 Irving Ave., Syracuse, NY 13210.

References

1. Boden WE. Investigation and treatment of the patient with non-Q-wave myocardial infarction. In: Roberts R, ed. Coronary heart disease and risk factors. Vol. 3 of Clinical cardiovascular therapeutics. Mount Kisco, N.Y.: Futura Publishing, 1991:113-65. 
2. Boden WE, Roberts R. Prognosis and management of patients with non-Q-wave myocardial infarction. Prog Cardiol 1991;4(2):143-60.
3. Goldberg RJ, Gore JM, Alpert JS, Dalen JE. Non-Q wave myocardial infarction: recent changes in occurrence and prognosis -- a community-wide perspective. Am Heart J 1987;113:273-279. [Erratum, Heart J 1987;114:1535.] [CrossRef][Medline]
4. Gibson RS. Non-Q-wave myocardial infarction: diagnosis, prognosis, and management. Curr Probl Cardiol 1988;13:9-72. [Medline]
5. Gibson RS. Non-Q-wave myocardial infarction. In: Fuster V, Ross R, Topol EJ, eds. Atherosclerosis and coronary artery disease. Vol. 2. Philadelphia: Lippincott-Raven, 1996:1097-123.
6. Klein LW, Helfant RH. The Q-wave and non-Q-wave myocardial infarction: differences and similarities. Prog Cardiovasc Dis 1986;29:205-220. [CrossRef][Medline]
7. Liebson PR, Klein LW. The non-Q wave myocardial infarction revisited: 10 years later. Prog Cardiovasc Dis 1997;39:399-444. [CrossRef][Medline]
8. Marmor A, Sobel BE, Roberts R. Factors presaging early recurrent myocardial infarction ("extension"). Am J Cardiol 1981;48:603-610. [CrossRef][Medline]
9. Nicod P, Gilpin E, Dittrich H, et al. Short- and long-term clinical outcome after Q wave and non-Q wave myocardial infarction in a large patient population. Circulation 1989;79:528-536. [Free Full Text]
10. Chung MK, Bosner MS, McKenzie JP, Shen J, Rich MW. Prognosis of patients 70 years of age with non-Q-wave acute myocardial infarction compared with younger patients with similar infarcts and with patients 70 years of age with Q-wave acute myocardial infarction. Am J Cardiol 1995;75:18-22. [CrossRef][Medline]
11. Rich MW, Bosner MS, Chung MK, Shen J, McKenzie JP. Is age an independent predictor of early and late mortality in patients with acute myocardial infarction? Am J Med 1992;92:7-13. [CrossRef][Medline]
12. Maisel AS, Ahnve S, Gilpin E, et al. Prognosis after extension of myocardial infarct: the role of Q wave or non-Q wave infarction. Circulation 1985;71:211-217. [Free Full Text]
13. Bosch X, Theroux P, Waters DD, Pelletier GB, Roy D. Early postinfarction ischemia: clinical, angiographic, and prognostic significance. Circulation 1987;75:988-995. [Free Full Text]
14. Schechtman KB, Capone RJ, Kleiger RE, et al. Differential risk patterns associated with 3 month as compared with 3 to 12 month mortality and reinfarction after non-Q wave myocardial infarction: the Diltiazem Reinfarction Study Group. J Am Coll Cardiol 1990;15:940-947. [Abstract]
15. Cannon CP, Thompson B, McCabe CH, et al. Predictors of non-Q-wave acute myocardial infarction in patients with acute ischemic syndromes: an analysis from the Thrombolysis in Myocardial Ischemia (TIMI) III trials. Am J Cardiol 1995;75:977-981. [CrossRef][Medline]
16. Huey BL, Gheorghiade M, Crampton RS, et al. Acute non-Q wave myocardial infarction associated with early ST segment elevation: evidence for spontaneous coronary reperfusion and implications for thrombolytic trials. J Am Coll Cardiol 1987;9:18-25. [Abstract]
17. Guidelines for coronary angiography: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Subcommittee on Coronary Angiography). J Am Coll Cardiol 1987;10:935-950. [Medline]
18. Pepine CJ, Allen HD, Bashore TM, et al. American College of Cardiology/American Heart Association guidelines for cardiac catheterization and cardiac catheterization laboratories. J Am Coll Cardiol 1991;18:1149-1182. [Medline]
19. Ryan TJ, Anderson JL, Antman EM, et al. ACC/AHA guidelines for the management of patients with acute myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Acute Myocardial Infarction). J Am Coll Cardiol 1996;28:1328-1428. [CrossRef][Medline]
20. 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: Thrombolysis in Myocardial Ischemia. Circulation 1994;89:1545-1556. [Free Full Text]
21. Topol EJ, Califf RM, George BS, et al. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. N Engl J Med 1987;317:581-588. [Abstract]
22. The TIMI Research Group. Immediate vs delayed catheterization and angioplasty following thrombolytic therapy for acute myocardial infarction: TIMI II A results. JAMA 1988;260:2849-2858. [Abstract]
23. Rouleau JL, Moyé LA, Pfeffer MA, et al. A comparison of management patterns after acute myocardial infarction in Canada and the United States. N Engl J Med 1993;328:779-784. [Free Full Text]
24. Ferry DR, O'Rourke RA, Blaustein AS, et al. Design and baseline characteristics of the Veterans Affairs Non-Q-Wave Infarction Strategies In-Hospital (VANQWISH) trial. J Am Coll Cardiol 1998;31:312-320. [Free Full Text]
25. Boden WE, Kleiger RE, Gibson R, et al. Electrocardiographic and enzymatic findings in acute non-Q wave myocardial infarction. Am J Noninvasive Cardiol 1988;2:125-33.
26. Kleiger RE, Boden WE, Schechtman KB, et al. Frequency and significance of late evolution of Q-waves in patients with non-Q-wave acute myocardial infarction. Am J Cardiol 1990;65:23-27. [Medline]
27. Boden WE, Kleiger RE, Gibson RS, et al. Electrocardiographic evolution of posterior acute myocardial infarction: importance of early precordial ST-segment depression. Am J Cardiol 1987;59:782-787. [CrossRef][Medline]
28. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial. Biometrics 1975;31:103-115. [CrossRef][Medline]
29. Gibson RS, Boden WE, Theroux P, et al. Diltiazem and reinfarction in patients with non-Q-wave acute myocardial infarction: results of a double-blind, randomized, multicenter trial. N Engl J Med 1986;315:423-429. [Abstract]
30. The Multicenter Diltiazem Postinfarction Trial Research Group. The effect of diltiazem on mortality and reinfarction after myocardial infarction. N Engl J Med 1988;319:385-392. [Abstract]
31. Boden WE, Krone RJ, Kleiger RE, et al. Electrocardiographic subset analysis of diltiazem administration on long-term outcome after acute myocardial infarction: the Multicenter Diltiazem Post-Infarction Trial Research Group. Am J Cardiol 1991;67:335-342. [CrossRef][Medline]
32. Boden WE. Management of non-Q-wave myocardial infarction: role of diltiazem versus beta-blocker therapy. J Cardiovasc Pharmacol 1990;16:Suppl 6:S55-S60.
33. Makuch R, Simon R. Sample size requirements for evaluating a conservative therapy. Cancer Treat Rep 1978;62:1037-1040. [Medline]
34. The Multicenter Postinfarction Research Group. Risk stratification and survival after myocardial infarction. N Engl J Med 1983;309:331-336. [Abstract]
35. Lan KKG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika 1983;70:659-663. [Free Full Text]
36. O'Brien PC, Fleming TR. A multiple testing procedure for clinical trials. Biometrics 1979;35:549-556. [CrossRef][Medline]
37. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
38. Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
39. Madsen JK, Grande P, Saunamaki K, et al. Danish multicenter randomized study of invasive versus conservative treatment in patients with inducible ischemia after thrombolysis in acute myocardial infarction (DANAMI). Circulation 1997;96:748-755. [Free Full Text]
40. Tu JV, Sykora K, Naylor CD. Assessing the outcomes of coronary artery bypass graft surgery: how many risk factors are enough? J Am Coll Cardiol 1997;30:1317-1323. [Abstract]
41. Jones RH, Hannan EL, Hammermeister KE, et al. Identification of preoperative variables needed for risk adjustment of short-term mortality after coronary artery bypass graft surgery: Working Group Panel on the Cooperative CABG Database Project. J Am Coll Cardiol 1996;28:1478-1487. [Abstract]
42. Edwards FH, Clark RE, Schwartz M. Coronary artery bypass grafting: the Society of Thoracic Surgeons National Database experience. Ann Thorac Surg 1994;57:12-19. [Abstract]
43. Magovern JA, Sakert T, Magovern GJ, et al. A model that predicts morbidity and mortality after coronary artery bypass graft surgery. J Am Coll Cardiol 1996;28:1147-1153. [Abstract]
44. Krumholz HM. Cardiac procedures, outcomes, and accountability. N Engl J Med 1997;336:1522-1523.

The following persons and institutions participated in the VANQWISH Trial: Study Chairman's Office (Syracuse, N.Y.): W. Boden (chairman), H. Dai and D. Joyce (project coordinators), and P. Crawford (program assistant); Veterans Affairs Medical Centers: Albuquerque — M. Crawford, M. Holland, K. Wagoner; Cincinnati — L. Wexler, V. Thomas; Fresno, Calif. — P. Deedwania, E. Carbajal, R. Kanefield; Gainesville, Fla. — C. Pepine, J. Green, Jr., M. Limacher, E. Handberg-Thurmond, N. Davis; Hines, Ill. — M. Hwang, S. Lemoine; Houston — A. Blaustein, C. Rowe; Lexington, Ky. — C. Chasen, P. Frazier; Little Rock, Ark. — M. Murphy, J. Doherty, E. Smith, III, J. Calkins, Jr., A. Bierle; Loma Linda, Calif. — D. Ferry, A. Jacobson, G. Frivold, K. Okubo; Nashville — R. Smith, S. Levine, R. Bruce; Palo Alto, Calif. — J. Giacomini, C. Stepp; Richmond, Va. — R. Jesse, A. Minisi, C. Murphy; San Antonio, Tex. — R. O'Rourke, A. Jain, C. Patterson; San Diego, Calif. — A. Maisel; Seattle — K. Lehmann, J. Caldwell, S. Ferris; St. Louis — H. Stratmann, L. Younis, L. Conwill; Tampa, Fla. — R. Zoble, G. Cintron, J. Sullebarger, J. Umberger; Cooperative Studies Program Coordinating Center (Palo Alto, Calif.): P. Lavori (chief); D. Bloch, B. Chow, M. Iwane, R. Thomas, A. Busette, L. Sheridan, R. Yezzi, S. Jones, J. King, K. Small; Cooperative Studies Program Clinical Research Pharmacy Coordinating Center (Albuquerque, N.M.): C. Haakenson, M. Miller, L. Guidarelli, L. Vasquez, F. Chacon, C. Tripp, G. Garcia, J. Price; Cooperative Studies Program Central Office: P. Huang, Washington, D.C., and J. Gold, Boston; Planning Committee: J. Abrams, University of New Mexico, Albuquerque; T. Bigger, Columbia University, New York; P. Carson, Georgetown University, Washington, D.C.; R. Kleiger, Jewish Hospital of St. Louis, St. Louis; J. Leppo, University of Massachusetts, Worcester; M. Moskowitz, Boston University, Boston; M. Smith, Veterans Affairs Medical Center, Manchester, N.H.; M. Hlatky, Stanford University, Stanford, Calif.; R. Thomas, Veterans Affairs Medical Center, Palo Alto, Calif.; End-Points Committee: C. Cannon (chairman), Brigham and Women's Hospital, Boston; K. Eagle, University of Michigan Medical Center, Ann Arbor; D. Losordo, St. Elizabeth's Hospital, Boston; Data Monitoring Board: B. Pitt (chairman), University of Michigan Medical Center, Ann Arbor; M. Moskowitz, University Hospital, Boston; A. Moss, University of Rochester Medical Center, Rochester, N.Y.; R. DeBusk, Stanford University School of Medicine, Palo Alto, Calif.; S. Azen, University of Southern California, Los Angeles; R. Schlant, Emory University School of Medicine, Atlanta; J. Wittes, Statistics Collaborative, Washington, D.C.; Core Laboratories: R. Kleiger, Electrocardiography Core Laboratory, Jewish Hospital–Washington University School of Medicine, St. Louis; J. Leppo, Nuclear Cardiology Quality Assessment Laboratory, University of Massachusetts Medical Center, Worcester; R. Kerensky, Coronary Angiography Quality Assessment Laboratory, University of Florida, Gainesville.

Abstract PDF Editorial by Lange, R. A. Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article Related Article by Malawer, M. M. PubMed Citation

Related Letters:

Management of Non–Q-Wave Myocardial Infarction
Bedell S. E., Graboys T. B., Ravid S., Thompson R. C., Roe M. T., Bowen T. E., Topol E. J., Huitink J. M., Bax J. J., Boden W. E., O'Rourke R. A., Crawford M. H.
Extract | Full Text  
N Engl J Med 1998; 339:1395-1398, Nov 5, 1998. Correspondence

This article has been cited by other articles:

• Dey, S, Flather, M D, Devlin, G, Brieger, D, Gurfinkel, E P, Steg, P G, FitzGerald, G, Jackson, E A, Eagle, K A, for the GRACE investigators, (2009). Sex-related differences in the presentation, treatment and outcomes among patients with acute coronary syndromes: the Global Registry of Acute Coronary Events. Heart 95: 20-26 [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]  
• 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]  
• Qayyum, R., Khalid, M. R., Adomaityte, J., Papadakos, S. P., Messineo, F. C. (2008). Systematic Review: Comparing Routine and Selective Invasive Strategies for the Acute Coronary Syndrome. ANN INTERN MED 148: 186-196 [Abstract] [Full Text]  
• Brown, M. L., Sundt, T. M. III, Gersh, B. J. (2008). Indications for Revascularization. Card Surg Adult 3: 551-572 [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]  
• Lin, G. A., Dudley, R. A., Redberg, R. F. (2007). Cardiologists' Use of Percutaneous Coronary Interventions for Stable Coronary Artery Disease. Arch Intern Med 167: 1604-1609 [Abstract] [Full Text]  
• Merhige, M. E., Breen, W. J., Shelton, V., Houston, T., D'Arcy, B. J., Perna, A. F. (2007). Impact of Myocardial Perfusion Imaging with PET and 82Rb on Downstream Invasive Procedure Utilization, Costs, and Outcomes in Coronary Disease Management. JNM 48: 1069-1076 [Abstract] [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]  
• 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]  
• 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]  
• 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]  
• 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]  
• 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]  
• James, S. K., Lindback, J., Tilly, J., Siegbahn, A., Venge, P., Armstrong, P., Califf, R., Simoons, M. L., Wallentin, L., Lindahl, B. (2006). Troponin-T and N-Terminal Pro-B-Type Natriuretic Peptide Predict Mortality Benefit From Coronary Revascularization in Acute Coronary Syndromes: A GUSTO-IV Substudy. J Am Coll Cardiol 48: 1146-1154 [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]  
• Carbajal, E. V. (2005). Routine vs Selective Invasive Strategies in Acute Coronary Syndromes. JAMA 294: 2845-2845 [Full Text]  
• Bavry, A. A., Kumbhani, D. J. (2005). Routine vs Selective Invasive Strategies in Acute Coronary Syndromes. JAMA 294: 2844-2845 [Full Text]  
• King, S. B. III (2005). Angioplasty Is Better Than Medical Therapy for Alleviating Chronic Angina Pectoris. Arch Intern Med 165: 2589-2592 [Full Text]  
• Liistro, F., Ducci, K., Falsini, G., Bolognese, L. (2005). Early invasive strategy in elderly patients with non-ST-elevation acute coronary syndromes. Eur Heart J Suppl 7: K23-K25 [Abstract] [Full Text]  
• de Winter, R. J., Windhausen, F., Cornel, J. H., Dunselman, P. H.J.M., Janus, C. L., Bendermacher, P. E.F., Michels, H. R., Sanders, G. T., Tijssen, J. G.P., Verheugt, F. W.A., the Invasive versus Conservative Treatment in Unst, (2005). Early Invasive versus Selectively Invasive Management for Acute Coronary Syndromes. NEJM 353: 1095-1104 [Abstract] [Full Text]  
• Mehta, S. R., Cannon, C. P., Fox, K. A. A., Wallentin, L., Boden, W. E., Spacek, R., Widimsky, P., McCullough, P. A., Hunt, D., Braunwald, E., Yusuf, S. (2005). Routine vs Selective Invasive Strategies in Patients With Acute Coronary Syndromes: A Collaborative Meta-analysis of Randomized Trials. JAMA 293: 2908-2917 [Abstract] [Full Text]  
• Bhatt, D. L. (2005). To Cath or Not to Cath: That Is No Longer the Question. JAMA 293: 2935-2937 [Full Text]  
• Onorati, F., Feo, M. D., Mastroroberto, P., Virgilio, A. d., Esposito, A., Polistena, M., Renzulli, A., Cotrufo, M. (2005). Unstable angina and non-ST segment elevation: surgical revascularization with different strategies. Eur. J. Cardiothorac. Surg. 27: 1043-1050 [Abstract] [Full Text]  
• Authors/Task Force Members, , Silber, S., Albertsson, P., Aviles, F. F., Camici, P. G., Colombo, A., Hamm, C., Jorgensen, E., Marco, J., Nordrehaug, J.-E., Ruzyllo, W., Urban, P., Stone, G. W., Wijns, W. (2005). Guidelines for Percutaneous Coronary Interventions: The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology. Eur Heart J 26: 804-847 [Full Text]  
• Large, G A (2005). Contemporary management of acute coronary syndrome. Postgrad. Med. J. 81: 217-222 [Abstract] [Full Text]  
• Stukel, T. A., Lucas, F. L., Wennberg, D. E. (2005). Long-term Outcomes of Regional Variations in Intensity of Invasive vs Medical Management of Medicare Patients With Acute Myocardial Infarction. JAMA 293: 1329-1337 [Abstract] [Full Text]  
• Van de Werf, F., Gore, J. M, Avezum, A., Gulba, D. C, Goodman, S. G, Budaj, A., Brieger, D., White, K., Fox, K. A A, Eagle, K. A, Kennelly, B. M, for the GRACE Investigators, (2005). Access to catheterisation facilities in patients admitted with acute coronary syndrome: multinational registry study. BMJ 330: 441- [Abstract] [Full Text]  
• Plein, S., Greenwood, J. P., Ridgway, J. P., Cranny, G., Ball, S. G., Sivananthan, M. U. (2004). Assessment of non-ST-segment elevation acute coronary syndromes with cardiac magnetic resonance imaging. J Am Coll Cardiol 44: 2173-2181 [Abstract] [Full Text]  
• Bhatt, D. L., Roe, M. T., Peterson, E. D., Li, Y., Chen, A. Y., Harrington, R. A., Greenbaum, A. B., Berger, P. B., Cannon, C. P., Cohen, D. J., Gibson, C. M., Saucedo, J. F., Kleiman, N. S., Hochman, J. S., Boden, W. E., Brindis, R. G., Peacock, W. F., Smith,, S. C. Jr, Pollack,, C. V. Jr, Gibler, W. B., Ohman, E. M., for the CRUSADE Investigators, (2004). Utilization of Early Invasive Management Strategies for High-Risk Patients With Non-ST-Segment Elevation Acute Coronary Syndromes: Results From the CRUSADE Quality Improvement Initiative. JAMA 292: 2096-2104 [Abstract] [Full Text]  
• Cannon, C. P. (2004). Revascularisation for everyone?. Eur Heart J 25: 1471-1472 [Full Text]  
• Ottervanger, J.P., Armstrong, P., Barnathan, E.S., Boersma, E., Cooper, J.S., Ohman, E.M., James, S., Wallentin, L., Simoons, M.L., For the GUSTO IV-ACS Investigators, (2004). Association of revascularisation with low mortality in non-ST elevation acute coronary syndrome, a report from GUSTO IV-ACS. Eur Heart J 25: 1494-1501 [Abstract] [Full Text]  
• Arai, A. E., Hirsch, G. A. (2004). Q-wave and non-q-wave myocardial infarctions through the eyes of cardiac magnetic resonance imaging. J Am Coll Cardiol 44: 561-563 [Full Text]  
• Bach, R. G., Cannon, C. P., Weintraub, W. S., DiBattiste, P. M., Demopoulos, L. A., Anderson, H. V., DeLucca, P. T., Mahoney, E. M., Murphy, S. A., Braunwald, E. (2004). The Effect of Routine, Early Invasive Management on Outcome for Elderly Patients with Non-ST-Segment Elevation Acute Coronary Syndromes. ANN INTERN MED 141: 186-195 [Abstract] [Full Text]  
• Udelson, J E, Flint, E J (2004). Radionuclide imaging in risk assessment after acute coronary syndromes. Heart 90: v16-v25 [Full Text]  
• Nagarajan, D. V., Lewis, P. S., Maguire, M., Dunning, J. (2004). Is an early invasive approach superior to a conservative strategy in patients with acute coronary syndrome?. ICVTS 3: 363-367 [Abstract] [Full Text]  
• Sabatine, M. S., Morrow, D. A., Giugliano, R. P., Murphy, S. A., Demopoulos, L. A., DiBattiste, P. M., Weintraub, W. S., McCabe, C. H., Antman, E. M., Cannon, C. P., Braunwald, E. (2004). Implications of Upstream Glycoprotein IIb/IIIa Inhibition and Coronary Artery Stenting in the Invasive Management of Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Comparison of the Thrombolysis In Myocardial Infarction (TIMI) IIIB Trial and the Treat angina with Aggrastat and determine Cost of Therapy with Invasive or Conservative Strategy (TACTICS)-TIMI 18 Trial. Circulation 109: 874-880 [Abstract] [Full Text]  
• Yang, H., Pu, M., Rodriguez, D., Underwood, D., Griffin, B. P., Kalahasti, V., Thomas, J. D., Brunken, R. C. (2004). Ischemic and viable myocardium in patients with Non-Q-Wave or Q-Wave myocardial infarction and left ventricular dysfunction: A clinical study using positron emission tomography, echocardiography, and electrocardiography. J Am Coll Cardiol 43: 592-598 [Abstract] [Full Text]  
• Lavori, P. W, Dawson, R. (2004). Dynamic treatment regimes: practical design considerations. Clin Trials 1: 9-20 [Abstract]  
• Braunwald, E. (2003). Application of Current Guidelines to the Management of Unstable Angina and Non-ST-Elevation Myocardial Infarction. Circulation 108: III-28-37 [Abstract] [Full Text]  
• Neumann, F.-J., Kastrati, A., Pogatsa-Murray, G., Mehilli, J., Bollwein, H., Bestehorn, H.-P., Schmitt, C., Seyfarth, M., Dirschinger, J., Schomig, A. (2003). Evaluation of Prolonged Antithrombotic Pretreatment ("Cooling-Off" Strategy) Before Intervention in Patients With Unstable Coronary Syndromes: A Randomized Controlled Trial. JAMA 290: 1593-1599 [Abstract] [Full Text]  
• Desideri, A., Fioretti, P. M., Cortigiani, L., Gregori, D., Coletta, C., Vigna, C., Tota, F., Rambaldi, R., Bax, J., Celegon, L., Bigi, R., Picano, E., on behalf of the COSTAMI Trial Investigators, (2003). Cost of strategies after myocardial infarction (COSTAMI): A multicentre, international, randomized trial for cost-effective discharge after uncomplicated myocardial infarction. Eur Heart J 24: 1630-1639 [Abstract] [Full Text]  
• Gupta, M., Chang, W.-C., Van de Werf, F., Granger, C. B., Midodzi, W., Barbash, G., Pehrson, K., Oto, A., Toutouzas, P., Jansky, P., Armstrong, P. W., for the ASSENT II Investigators, (2003). International differences in in-hospital revascularization and outcomes following acute myocardial infarction: A multilevel analysis of patients in ASSENT-2. Eur Heart J 24: 1640-1650 [Abstract] [Full Text]  
• Williams, I. L, Noronha, B., Zaman, A. G (2003). Review: The management of acute myocardial infarction in patients with diabetes mellitus. British Journal of Diabetes & Vascular Disease 3: 319-324 [Abstract]  
• Prasad, A., Mathew, V., Holmes, D. R Jr., Gersh, B. J (2003). Current management of non-ST-segment-elevation acute coronary syndrome: reconciling the results of randomized controlled trials. Eur Heart J 24: 1544-1553 [Abstract] [Full Text]  
• Barrabes, J. A., Figueras, J., Moure, C., Cortadellas, J., Soler-Soler, J. (2003). Prognostic Value of Lead aVR in Patients With a First Non-ST-Segment Elevation Acute Myocardial Infarction. Circulation 108: 814-819 [Abstract] [Full Text]  
• O'Neill, W. W. (2003). "Watchful waiting"after thrombolysis: It's time for a re-evaluation. J Am Coll Cardiol 42: 17-19 [Full Text]  
• Hyde, T A, French, J K, Wong, C-K, Edwards, C, Whitlock, R M L, White, H D (2003). Associations between ST depression, four year mortality, and in-hospital revascularisation in unselected patients with non-ST elevation acute coronary syndromes. Heart 89: 490-495 [Abstract] [Full Text]  
• Gabriel Steg, P., Iung, B., Feldman, L. J, Maggioni, A. P, Keil, U., Deckers, J., Cokkinos, D., Fox, K. A.A, for the ENACT investigators, (2003). Determinants of use and outcomes of invasive coronary procedures in acute coronary syndromes: results from ENACT. Eur Heart J 24: 613-622 [Abstract] [Full Text]  
• Thambyrajah, J, De Belder, M.A (2003). Management of non ST-segment elevation acute coronary syndromes--continuing the search for the bad guys. Eur Heart J 24: 490-493 [Full Text]  
• Boden, W. E., Pepine, C. J. (2003). Introduction to "optimizing management of non-ST-segment elevation acute coronary syndromes": Harmonizing advances in mechanical and pharmacologic intervention. J Am Coll Cardiol 41: 1S-6S [Full Text]  
• Cannon, C. P. (2003). Small molecule glycoprotein IIb/IIIa receptor inhibitors as upstream therapy in acute coronary syndromes: Insights from the TACTICS TIMI-18 trial. J Am Coll Cardiol 41: 43S-48S [Abstract] [Full Text]  
• McKay, R. G. (2003). "Ischemia-guided" versus "early invasive" strategies in the management of acute coronary syndrome/non-ST-segment elevation myocardial infarction: The interventionalist's perspective. J Am Coll Cardiol 41: 96S-102S [Abstract] [Full Text]  
• Nissen, S. E. (2003). Pathobiology, not angiography, should guide managementin acute coronary syndrome/non-ST-segment elevation myocardial infarction: The non-interventionist's perspective. J Am Coll Cardiol 41: 103S-112S [Abstract] [Full Text]  
• Boden, W. E. (2003). "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 41: 113S-122S [Abstract] [Full Text]  
• Kennon, S, Price, C P, Mills, P G, MacCallum, P K, Cooper, J, Hooper, J, Clarke, H, Timmis, A D (2003). Cumulative risk assessment in unstable angina: clinical, electrocardiographic, autonomic, and biochemical markers. Heart 89: 36-41 [Abstract] [Full Text]  
• Sundt, T. M. III, Gersh, B. J., Smith, H. C. (2003). Indications for Coronary Revascularization. Card Surg Adult 2: 541-559 [Full Text]  
• Boden, W. E., VANQWISH Trial Core Angiographic Laboratory Invest, (2002). Reply. J Am Coll Cardiol 40: 2205-2206 [Full Text]  
• Lagerqvist, B. o, Husted, S., Kontny, F., Naslund, U., Stahle, E., Swahn, E., Wallentin, L., FRISC-II Investigators, (2002). 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 40: 1902-1914 [Abstract] [Full Text]  
• Yarlagadda, R. K., Boden, W. E. (2002). Cardioprotective effects of an early invasive strategy for non-ST-segment elevationacute coronary syndromes: Are we all becoming "interventional" cardiologists?. J Am Coll Cardiol 40: 1915-1918 [Full Text]  
• Sheridan, P J, Crossman, D C (2002). Critical review of unstable angina and non-ST elevation myocardial infarction. Postgrad. Med. J. 78: 717-726 [Abstract] [Full Text]  
• Neumann, F.-J., Jander, N. (2002). How to best counteract the enemies? By ensuring adequate oxygen delivery. Eur Heart J Suppl 4: G35-G42 [Abstract]  
• Mahoney, E. M., Jurkovitz, C. T., Chu, H., Becker, E. R., Culler, S., Kosinski, A. S., Robertson, D. H., Alexander, C., Nag, S., Cook, J. R., Demopoulos, L. A., DiBattiste, P. M., Cannon, C. P., Weintraub, W. S., for the TACTICS-TIMI 18 Investigators, (2002). Cost and Cost-effectiveness of an Early Invasive vs Conservative Strategy for the Treatment of Unstable Angina and Non-ST-Segment Elevation Myocardial Infarction. JAMA 288: 1851-1858 [Abstract] [Full Text]  
• Cohen, D. J. (2002). Invasive vs Conservative Management of Acute Coronary Syndromes: Do the Data Support the Guidelines?. JAMA 288: 1905-1907 [Full Text]  
• Rathore, S. S., Wang, Y., Radford, M. J., Ordin, D. L., Krumholz, H. M. (2002). Sex Differences in Cardiac Catheterization after Acute Myocardial Infarction: The Role of Procedure Appropriateness. ANN INTERN MED 137: 487-493 [Abstract] [Full Text]  
• Verheugt, F.W.A. (2002). Low molecular weight heparin: a bridge over troubled water. Eur Heart J 23: 1144-1146 [Full Text]  
• Chang, W.-C., Harrington, R.A., Simoons, M.L., Califf, R.M., Lincoff, A.M., Armstrong, P.W. (2002). Does eptifibatide confer a greater benefit to patients with unstable angina than with non-ST segment elevation myocardial infarction?. Insights from the PURSUIT Trial. Eur Heart J 23: 1102-1111 [Abstract] [Full Text]  
• Ferreiros, E.R., Kevorkian, R., Fuselli, J.J., Guetta, J., Boissonnet, C.P., di Toro, D., Cragnolino, R., Masoli, O., Cagide, A., Krauss, J. (2002). First national survey on management strategies in non ST-elevation acute ischaemic syndromes in Argentina. Results of the STRATEG-SIA study. Eur Heart J 23: 1021-1029 [Abstract] [Full Text]  
• Sicari, R., Landi, P., Picano, E., Pirelli, S., Chiaranda, G., Previtali, M., Seveso, G., Gandolfo, N., Margaria, F., Magaia, O., Minardi, G., Mathias, W. (2002). Exercise-electrocardiography and/or pharmacological stress echocardiography for non-invasive risk stratification early after uncomplicated myocardial infarction. A prospective international large scale multicentre study. Eur Heart J 23: 1030-1037 [Abstract] [Full Text]  
• Goyal, A., Samaha, F. F., Boden, W. E., Wade, M. J., Kimmel, S. E. (2002). Stress test criteria used in the conservative arm of the frisc-ii trial underdetects surgical coronary artery disease whenapplied to patients in the vanqwish trial. J Am Coll Cardiol 39: 1601-1607 [Abstract] [Full Text]  
• Kerensky, R. A., Wade, M., Deedwania, P., Boden, W. E., Pepine, C. J., Veterans Affairs Non-Q-Wave Infarction Strategies, (2002). Revisiting the culprit lesion in non-Q-wave myocardial infarction: Results from the VANQWISH trial angiographic core laboratory. J Am Coll Cardiol 39: 1456-1463 [Abstract] [Full Text]  
• Ferguson, J.J. (2002). Antithrombin therapy, antiplatelet therapy and percutaneous coronary intervention: rationale and design of the SYNERGY trial. Eur Heart J Suppl 4: E2-E9 [Abstract]  
• Pilote, L., Lauzon, C., Huynh, T., Dion, D., Roux, R., Racine, N., Carignan, S., Diodati, J. G., Levesque, C., Charbonneau, F., Pouliot, J., Joseph, L., Eisenberg, M. J. (2002). Quality of Life After Acute Myocardial Infarction Among Patients Treated at Sites With and Without On-site Availability of Angiography. Arch Intern Med 162: 553-559 [Abstract] [Full Text]  
• Mark, D. B., Lee, T. H. (2002). Conservative Management of Acute Coronary Syndrome: Cheaper and Better for You?. Circulation 105: 666-668 [Full Text]  
• Phibbs, B. P.