(Circulation. 1997;95:2037-2043.)
© 1997 American Heart Association, Inc.
Articles |
Asymptomatic Cardiac Ischemia Pilot (ACIP) Study Two-Year Follow-up
Outcomes of Patients Randomized to Initial Strategies of Medical Therapy Versus Revascularization
From the Division of Cardiology, Department of Medicine, University of Ottawa (Ontario) Heart Institute, and Ottawa Civic Hospital.
Correspondence to Dr Richard F. Davies, Room H147, University of Ottawa Heart Institute, 1053 Carling Ave, Ottawa, Ontario, Canada K1Y 4E9. E-mail rfdavies{at}heartinst.on.ca
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background Patients with ischemia during stress testing and ambulatory ECG monitoring have an increased risk of cardiac events, but it is not known whether their prognosis is improved by more aggressive treatment with anti-ischemic drugs or revascularization.
Methods and Results The Asymptomatic Cardiac Ischemia Pilot study randomized 558 such patients who had coronary anatomy suitable for revascularization to three treatment strategies: angina-guided drug therapy (n=183), angina plus ischemia–guided drug therapy (n=183), or revascularization by angioplasty or bypass surgery (n=192). Two years after randomization, the total mortality was 6.6% in the angina-guided strategy, 4.4% in the ischemia-guided strategy, and 1.1% in the revascularization strategy (P<.02). The rate of death or myocardial infarction was 12.1% in the angina-guided strategy, 8.8% in the ischemia-guided strategy, and 4.7% in the revascularization strategy (P<.04). The rate of death, myocardial infarction, or recurrent cardiac hospitalization was 41.8% in the angina-guided strategy, 38.5% in the ischemia-guided strategy, and 23.1% in the revascularization strategy (P<.001). Pairwise testing revealed significant differences between the revascularization and angina-guided strategies for each comparison.
Conclusions A strategy of initial revascularization appears to improve the prognosis of this population compared with angina-guided medical therapy. A larger long-term study is needed to confirm this benefit and to adequately test the potential of more aggressive drug therapy.
Key Words: prognosis • electrocardiography • coronary disease • revascularization • survival • drugs
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
In patients with coronary disease, ischemia during stress testing and AECG monitoring predicts a worsened prognosis.1 2 It is not known whether this is improved by aggressive treatment aimed at reducing ischemia. The NHLBI-sponsored ACIP Study (for list of participants, see Reference 33 ) was conducted to see whether a larger trial addressing this question was feasible. ACIP compared the relative efficacies of three treatment strategies in suppressing ischemia: (1) angina-guided drug therapy, (2) angina plus AECG ischemia–guided drug therapy, and (3) revascularization by either PTCA or CABG.
We previously reported that the revascularization strategy was more effective than either the angina-guided or ischemia-guided drug strategy in suppressing ischemia at 12 weeks and 1 year after randomization and was associated with a reduced 1-year mortality and morbidity.3 4 This report describes the 2-year clinical outcomes associated with these three treatment strategies.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
The ACIP methodology and trial design have been published previously.5 The target population was clinically stable patients with angiographically documented coronary disease (
50% stenosis in 1 major vessel or branch) suitable for
revascularization. To be eligible, patients also
had to have ischemia during exercise or pharmacological stress
testing and at least one episode of asymptomatic
ischemia during 48-hour AECG monitoring. Patients either were
free of angina or had symptoms that could be well controlled by medical
therapy. Patients with recent MI or unstable angina or who were unable
to tolerate at least one of the two prespecified medical treatments
were excluded. The ACIP protocol and consent forms were approved by the
responsible institutional review boards. All patients provided informed
consent before enrollment. An independent data and safety monitoring
board reviewed clinical outcomes and the conduct and safety of the
trial at 6-month intervals. Patients were randomized to one of three initial treatment strategies: angina-guided medical treatment, ischemia-guided medical treatment, or revascularization. The angina-guided strategy consisted of anti-ischemic drug treatment sufficient to control angina. The ischemia-guided strategy added additional active drug therapy if ischemia was still present during AECG recording. Patients in the angina-guided strategy received placebo to maintain blinding. The revascularization strategy consisted of initial treatment with PTCA or CABG aimed at achieving the most complete revascularization possible by the method deemed most appropriate by the physician at the clinical site. After randomization, open-label active medication or nonprotocol revascularization was permitted as necessary to control angina.
Protocol anti-ischemic drug therapy consisted of titrated regimens of atenolol with addition of controlled-release nifedipine if needed or of sustained-release diltiazem with addition of sustained-release isosorbide dinitrate if needed. During the first 4 weeks after randomization, open-label medications were titrated upward to control angina if it was present. During the subsequent 8 weeks, placebo (angina-guided strategy) or active drug (ischemia-guided strategy) was added if ischemia was still present on repeat 48-hour AECG recordings. All patients received aspirin unless contraindicated. Patients were maintained on assigned treatment for a period of 1 year, at which time they were withdrawn from study medication and treated as deemed necessary by their physician.
Clinical Characteristics and Outcome Assessment
Prespecified clinical outcomes included death, MI, recurrent
hospitalization for cardiac disease, and nonprotocol
revascularization. An independent committee unaware
of treatment assignment classified outcomes occurring within 1 year of
enrollment using prespecified definitions. Outcomes occurring during
the second year were reported as determined by the clinical sites and
were not reviewed centrally.
Statistical Analysis
Data are reported for 558 patients randomized in 10 clinical
centers6 for whom follow-up was 100% complete at 1 year
and 97% complete at 2 years. On the final data edit, it was noted that
7 randomized patients should have been excluded for the following
reasons: MI within 4 weeks (n=2, angina-guided strategy), PTCA within
the previous 6 months (n=5: 2 in the angina-guided strategy, 2 in the
ischemia-guided strategy, and 1 in the
revascularization strategy). In addition, 22
patients in the revascularization strategy did not
have PTCA or CABG within the specified time window. Analyses
included these patients in their assigned groups according to the
intention-to-treat principle.
Adverse outcomes were classified according to the following
hierarchical scheme: (1) death; (2) death or MI; and (3) death, MI, or
hospitalization for a cardiac condition. The latter included
nonprotocol revascularization and any cardiac
complication associated with a noncardiovascular
admission. Outcome rates were calculated by Kaplan-Meier life table
methods and compared by the log-rank test. Because of the risk of type
1 error with multiple post hoc comparisons, it was specified during the
planning of ACIP that a value of 
=.01 would be taken as showing some
evidence for a significant difference and a value of =.001 would be
taken as showing strong evidence for a significant difference.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Baseline Characteristics
Table 1
summarizes the baseline characteristics of
the 558 randomized patients, and Table 2 summarizes
baseline exercise testing and AECG monitoring data. Complete reports of
baseline data have been published previously.3 Groups were
well matched with regard to important baseline variables. Overall,
89% of randomized patients were receiving aspirin: 89% in the
angina-guided strategy, 90% in the ischemia-guided strategy,
and 88% in the revascularization strategy. During
baseline treadmill exercise testing, there was a nonsignificant
tendency toward more strongly positive ischemic responses in
the revascularization strategy. In each group, 33%
of patients had angina during baseline treadmill exercise testing; the
remainder had asymptomatic ischemia. During
baseline AECG monitoring, there was a tendency for the
revascularization group to have more episodes and a
greater total ischemic time. Only 61 of 558 patients (11%) had
symptomatic as well as asymptomatic
episodes.
|
|
Protocol Drug Treatment
Compared with the angina-guided strategy, patients randomized to
the ischemia-guided strategy received significantly more active
anti-ischemic medication, and those randomized to the
revascularization strategy received significantly
less.3 At 1 year, among patients assigned to receive
atenolol plus nifedipine, the mean daily dose of active
medication for the angina-guided strategy was atenolol 64 mg and
nifedipine 42 mg; for the ischemia-guided strategy,
atenolol 128 mg and nifedipine 58 mg; and for the
revascularization strategy, atenolol 65 mg and
nifedipine 46 mg. Among those assigned to receive diltiazem
plus isosorbide dinitrate, the mean daily dose of active medication for
the angina-guided strategy was diltiazem 170 mg and isosorbide
dinitrate 69 mg; for the ischemia-guided strategy, diltiazem
276 mg and isosorbide dinitrate 86 mg; and for the
revascularization strategy, diltiazem 159 mg and
isosorbide dinitrate 58 mg.
Protocol Revascularization
Within the revascularization strategy, PTCA
was selected for 102 patients and CABG for 90 patients. Eight patients
selected for PTCA subsequently refused the procedure, and 2 had the
procedure outside of the specified time window (which was 6 weeks for
staged PTCA, 4 weeks otherwise). This left 92 patients who underwent
protocol PTCA within the specified time window. Eleven patients
selected for CABG subsequently refused the procedure, and 1 had the
procedure outside of the 4-week time window. This left 78 patients who
underwent protocol CABG within the specified time window. All
randomized patients were included in their assigned treatment groups
for statistical analysis according to the intention-to-treat
principle.
Clinical Outcomes
Figs 1 through 3 show 2-year event rates for the three treatment
strategies. Mortality for the angina-guided strategy was 6.6%, for the
ischemia-guided strategy 4.4%, and for the
revascularization strategy 1.1% (Fig 1). Pairwise testing showed the difference between the
angina-guided and revascularization strategies to
be significant at the P<.005 level. The differences between
the ischemia-guided and revascularization
strategies (P=.05) and between the angina-guided and
ischemia-guided strategies (P=.34) were not
significant by ACIP predefined criteria.
|
|
|
Rates for the end point of death or myocardial infarction were 12.1%
for the angina-guided strategy, 8.8% for the ischemia-guided
strategy, and 4.7% for the revascularization
strategy (Fig 2
). Pairwise testing revealed the
difference between the angina-guided and
revascularization strategy to be significant at the
P<.01 level. Differences were not significant between the
angina-guided and ischemia-guided strategies (P=.30)
or between the ischemia-guided and
revascularization strategies
(P=.12).
Rates for the end point of death, myocardial infarction, or recurrent
hospitalization (including nonprotocol
revascularization) were 41.8% for the
angina-guided strategy, 38.5% for the ischemia-guided
strategy, and 23.1% for the revascularization
strategy (Fig 3). Pairwise testing revealed the
differences between the revascularization strategy
and both the angina-guided and ischemia-guided strategies to be
significant at the P<.005 level. The angina-guided and
ischemia-guided strategies were not significantly different
from each other (P=.48).
Table 3 shows the 2-year event frequencies for each
strategy and the calculated reduction in event rates for the
ischemia-guided and revascularization
strategies relative to the angina-guided strategy.
|
As noted above, 170 of the 192 patients assigned to the revascularization strategy underwent the assigned procedure within the prespecified time window. Of the 92 undergoing PTCA, 2-year event rates were 1.1% (1 patient) for mortality; 5.5% (5 patients) for death or MI; and 31.7% (29 patients) for death, MI, or recurrent hospitalization. The corresponding rates for the 78 patients undergoing CABG were 0% for mortality; 2.7% (2 patients) for death or MI; and 12.9% (10 patients) for death, MI, or hospitalization. When patients undergoing PTCA and CABG were compared, differences were statistically significant only for the latter end point (death, MI, or hospitalization; P=.005). Among the medical treatment groups, there were no significant differences in any of these end points between patients assigned to diltiazem/isosorbide dinitrate and those assigned to atenolol/nifedipine.
Nonprotocol Revascularization
As shown in Table 4, the 2-year rates of
nonprotocol revascularization were 29% for both
medical treatment strategies and 11% for the
revascularization strategy. Most of this difference
was because of a lower rate of recurrent CABG in the
revascularization strategy.
|
Risk Reduction in Angiographic Subgroups
Table 5 shows the 2-year frequency of adverse
clinical outcomes in different angiographic subgroups. Patients with at
least 50% stenosis in the proximal LAD who were randomized to
a medical treatment strategy had higher event rates than did patients
without a significant proximal LAD stenosis. This was not the
case for patients randomized to the
revascularization strategy. The data suggest a
tendency for the benefit of revascularization to be
concentrated in those with proximal LAD stenoses
(P=.013 for difference between relative risks). There was a
similar tendency in patients with three-vessel disease compared with
those with one- or two-vessel disease (P=.015 for difference
between relative risks).
|
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
These results indicate that initial revascularization may substantially improve the 2-year prognosis of patients with objective evidence of ischemia and suitable coronary anatomy, even if their angina is well controlled on conservative medical therapy. There have been three major previous trials of revascularization and prognosis: CASS, the VA Study, and the European Study. Both CASS and the VA Study reported an overall negative effect of CABG on survival,7 8 whereas the European Study showed an overall benefit.9 A recent meta-analysis also found an overall survival benefit of CABG.10 This meta-analysis and individual subgroup analyses of the three major trials11 12 13 14 suggested that improvement in prognosis is concentrated in specific high-risk subgroups. Consequently, it is currently accepted that bypass surgery improves survival in patients with left main coronary artery disease and in those with left ventricular dysfunction who have two- or three-vessel disease involving the proximal LAD.15 Such patients were not included in ACIP. No patient had left main disease >50%, and only 5% had the combination of LAD stenosis and ejection fraction <50%. The results therefore indicate that revascularization may be indicated to improve prognosis in a broader group of patients.
Previous studies of CABG and prognosis were begun in the 1970s and early 1980s, and their results reflect the surgical and medical approaches in use at that time. Their results may underestimate the benefits of revascularization by current techniques, which now include internal thoracic artery grafts and other arterial conduits, improved methods of myocardial preservation, and the routine postoperative use of aspirin. PTCA, which currently accounts for approximately half of revascularization procedures, was not yet available when these previous trials were initiated. By contrast, ACIP revascularization was done between November 1991 and January 1993 using currently accepted techniques, with the goal of achieving as complete revascularization as possible. Until a larger study is completed, ACIP provides the best available data regarding revascularization for prognosis and the only randomized data comparing reasonably current techniques with medical therapy.
Implications of ACIP Design
This study compares the clinical outcomes for three initial
therapeutic strategies according to the intention-to-treat principle.
For patients who could not be adequately controlled despite maximal
medical therapy, revascularization could be
considered. Consequently, 29% of patients randomized to medical
treatment strategies underwent nonprotocol
revascularization during the 2 years of follow-up.
Because "crossovers" would tend to diminish differences between
medical and revascularization strategies, the
design of ACIP is unlikely to have exaggerated the benefits
of revascularization. Examining the outcomes
associated with different therapeutic options exercised at a given
point in time is also the most clinically relevant comparison.
Limitations
ACIP was a pilot study. As such, it was not planned to have
sufficient statistical power to detect differences in clinical
outcomes. The difference between the angina-guided and
revascularization strategies in 2-year mortality is
based on only 14 deaths (12 in the angina-guided strategy and 2 in the
revascularization strategy). The results for death
or nonfatal MI are based on only 31 events (22 in the angina-guided
strategy and 9 in the revascularization strategy).
Although the dramatic differences seen produced a statistically
significant result, there are too few events to allow for an accurate
measurement of effect size. Therefore, although we observed a sixfold
difference in mortality in favor of
revascularization over conservative medical
therapy, the confidence bounds around this estimate are wide.
Previous studies of revascularization showed that the patients most likely to benefit from revascularization are those who have the greatest risk of cardiac events with medical therapy.10 ACIP used the combination of stress testing and AECG monitoring to identify high-risk patients. However, this may not be the best way to select patients who will benefit from revascularization. Although several previous studies have shown that AECG monitoring identifies high-risk patients,1 2 other studies show that this may not be true in all populations.16 This raises the possibility that the requirement of ischemia during AECG monitoring in addition to ischemia during stress testing may be unnecessarily restrictive. It is also possible that another test or combination of tests might be more effective in selecting the appropriate high-risk subgroup. An ACIP substudy looked at the relation between AECG ischemia, stress single photon emission computed tomography perfusion imaging, and coronary anatomy.17 It found that the only predictor of AECG ischemia was the presence of ST depression during exercise testing, whereas the most important predictor of perfusion abnormalities was the severity of coronary stenoses on angiography. The present study found that those patients with proximal LAD stenoses and those with three-vessel disease tended to have higher event rates and to derive greater benefits from revascularization. It is therefore possible that nuclear perfusion imaging will prove useful in better characterizing which high-risk patients will benefit most from revascularization. The role of various tests in doing so remains an extremely important unresolved question that needs to be studied as part of a larger, adequately powered trial.
The small sample size of ACIP limited its ability to address the issue of whether more aggressive medical therapy improves prognosis. Clinical outcome rates for the ischemia-guided drug treatment strategy were intermediate between angina-guided drug therapy and revascularization. When the ischemia-guided strategy is compared with the angina-guided strategy, the observed reduction in mortality is 33% (4.4% versus 6.6%) and in death plus MI, 27% (8.8% versus 12.1%). Although these results were not statistically significant, these trends may be important, especially because the ACIP drug titration scheme did not maximize dosage in the ischemia-guided strategy.4 Because other studies have also provided supporting evidence for an influence of more aggressive anti-ischemic therapy on prognosis,18 19 this issue needs to be resolved by further research.
Another limitation of this study relates to the fact that ACIP
enrolled patients between 1991 and 1993, before the results of several
other important secondary prevention trials were available. These
studies have shown that aggressive cholesterol lowering
reduces AECG ischemia20 and improves the prognosis
of patients with known coronary disease.21 22 It
is therefore possible that aggressive cholesterol lowering
might reduce the apparent benefit of
revascularization. However, both the Scandinavian
Simvastatin Survival Study21 and the
Cholesterol and Recurrent Events Study22 found
that prognostic improvements with aggressive lipid-lowering therapy
were apparent only after 
2 years of therapy. The present study
indicates that revascularization has a more
immediate benefit, and the recently published NHLBI Post-CABG
study23 shows that lipid-lowering therapy also retards the
development of atherosclerosis in bypass grafts. Taken
together, these results suggest that future research will show that the
clinical benefits of lipid-lowering therapy and
revascularization are complementary.
Conclusions
Until a larger prognosis trial is done, ACIP provides the most
current data comparing a strategy of immediate
revascularization with conservative medical
therapy. The 2-year outcome data reported here are sobering in that, if
confirmed in a larger trial, they would significantly expand the
population for which revascularization is indicated
to improve prognosis. A larger study is therefore needed to confirm
this benefit using current revascularization
techniques in a setting of more aggressive lipid-lowering therapy and
to adequately test the prognostic potential of more aggressive
anti-ischemic drug therapy.
|
Selected Abbreviations and Acronyms |
|---|
|
|
Acknowledgments |
|---|
This study was funded by the National Heart, Lung, and Blood Institute, Division of Heart and Vascular Disease, National Institutes of Health, Bethesda, Md, by research contracts HV-90-07, HV-90-08, and HV-91-05 to HV-91-14. Study medications and placebo were donated by Zeneca Pharmaceuticals Group, Wilmington, Del; Marion-Merrell Dow, Kansas City, Mo; and Pfizer, New York, NY. Support for ECG data collection was provided in part by Applied Cardiac Systems, Laguna Hills, Calif; Marquette Electronics, Milwaukee, Wis; Mortara Instrument, Milwaukee, Wis; and Quinton Instruments, Seattle, Wash. Some centers had partial support from General Clinical Research Center grants. A complete list of the ACIP investigators and centers participating in the ACIP study was published previously.3
Received January 21, 1997; revision received February 24, 1997; accepted March 7, 1997.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Deedwania PC, Carbajal EV. Silent ischemia during daily life is an independent predictor of mortality in stable angina. Circulation. 1990;81:748-756.
2. Yeung AC, Barry J, Selwyn AP. Silent ischemia after myocardial infarction: prognosis, mechanism, and intervention. Circulation. 1990;82(suppl II):II-143-II-148.
3. Rogers WJ, Bourassa MG, Andrews TC, Bertolet BD, Blumenthal RS, Chaitman BR, Forman SA, Geller NL, Goldberg AD, Habib GB, Masters RG, Moisa RB, Mueller H, Pearce DJ, Pepine CJ, Sopko G, Steingart RM, Stone PH, Knatterud GL, Conti CR. Asymptomatic Cardiac Ischemia Pilot (ACIP) study: outcome at 1 year for patients with asymptomatic cardiac ischemia randomized to medical therapy or revascularization. J Am Coll Cardiol. 1995;26:594-605. [Abstract]
4. Knatterud GL, Bourassa MG, Pepine CJ, Geller NL, Sopko G, Chaitman BR, Pratt G, Stone PH, Davies RF, Rogers WJ, Deanfield JE, Goldberg AL, Ouyang P, Mueller H, Sharaf B, Day P, Selwyn AP, Conti CR, ACIP Investigators. Effects of treatment strategies to suppress ischemia in patients with coronary artery disease: 12-week results of the asymptomatic cardiac ischemia pilot (ACIP) study. J Am Coll Cardiol. 1994;24:11-20. [Abstract]
5. Pepine CJ, Geller NL, Knatterud GL, Bourassa MG, Chaitman BR, Davies RF, Day P, Deanfield JE, Goldberg AD, McMahon RP, Mueller H, Ouyang P, Pratt C, Proschan M, Rogers WJ, Sharaf B, Sopko G, Stone PH, Conti CR, ACIP Investigators. The Asymptomatic Cardiac Ischemia Pilot (ACIP) Study: design of a randomized clinical trial, baseline data and implications for a long-term outcome trial. J Am Coll Cardiol. 1994;24:1-10. [Abstract]
6. Conti CR, Knatterud GL, Sopko G. Correction. J Am Coll Cardiol. 1995;26:842.
7.
Coronary Artery Surgery Study (CASS) Principal
Investigators and Associates. Coronary Artery Surgery Study
(CASS): a randomized trial of coronary artery bypass surgery:
survival data. Circulation. 1983;68:939-950.
8. The Veterans Administration Coronary Artery Bypass Surgery Cooperative Study Group. Eleven-year survival in the Veterans Administration Randomized Trial of Coronary Bypass Surgery for Stable Angina Pectoris. N Engl J Med. 1984;311:1333-1337. [Abstract]
9. European Coronary Surgery Study Group. Long-term results of prospective randomised study of coronary artery bypass surgery in stable angina pectoris. Lancet. 1982;2:1173-1180. [Medline] [Order article via Infotrieve]
10. Yusuf S, Zucker D, Peduzzi P, Fisher LD, Takaro T, Kennedy JW, Davis K, Killip T, Passamani E, Norris R, Morris C, Mathur V, Vanauskas E, Chalmers TC. Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet. 1994;344:563-570. [Medline] [Order article via Infotrieve]
11.
Caracciolo EA, Davis KB, Sopko G, Kaiser GC, Corley SD,
Schaff H, Taylor HA, Chaitman BR. Comparison of surgical and
medical group survival in patients with left main equivalent
coronary artery disease: long-term CASS experience.
Circulation. 1995;91:2335-2344.
12. Zack PM, Chaitman BR, Davis KB, Kaiser GC, Wiens RD, Ng G. Survival patterns in clinical and angiographic subsets of medically treated patients with combined proximal left anterior descending and proximal left circumflex coronary artery disease (CASS). Am Heart J. 1989;118:220-227. [Medline] [Order article via Infotrieve]
13. Killip T, Passamani E, Davis K. Coronary Artery Surgery Study (CASS): a randomized trial of coronary bypass surgery: eight years follow-up and survival in patients with reduced ejection fraction. Circulation. 1985;72(pt 2):V-102-V-109.
14. Passamani E, Davis KB, Gillespie MJ, Killip T. A randomized trial of coronary artery bypass surgery: survival of patients with a low ejection fraction. N Engl J Med. 1985;312:1665-1671. [Abstract]
15.
American College of Cardiology/American
Heart Association Task Force on Assessment of Diagnostic
and Therapeutic Cardiovascular Procedures. ACC/AHA
guidelines and indications for coronary artery bypass graft
surgery. Circulation. 1991;83:1125-1173.
16.
Mulcahy D, Husain S, Zalos G, Rehman A, Andrews NP,
Schenke WH, Geller NL, Quyyumi AA. Ischemia during
ambulatory monitoring as a prognostic indicator in patients with stable
coronary artery disease. JAMA. 1997;277:318-324.
17. Mahmarian JJ, Steingart RM, Forman S, Sharaf BL, Coglianese ME, Miller DD, Pepine CJ, Goldbert AD, Bloom MF, Byers S, Dvorak L, Pratt CM, for the Asymptomatic Cardiac Ischemia Pilot (ACIP) Investigators. Relation between ambulatory electrocardiographic monitoring and myocardial perfusion imaging to detect coronary artery disease and myocardial ischemia: an ACIP ancillary study. J Am Coll Cardiol. In press.
18.
Pepine CJ, Cohn PF, Deedwania PC, Gibson RS, Handberg
E, Hill JA, Miller E, Marks RG, Thadani U, ASIST Study Group. Effects
of treatment on outcome in mildly symptomatic patients with
ischemia during daily life: the Atenolol Silent
Ischemia Study (ASIST). Circulation. 1994;90:762-768.
19.
Ruberman W, Crow R, Rosenberg CR, Rautaharju PM, Shore
RE, Pasternack BS. Intermittent ST depression and mortality
after myocardial infarction. Circulation. 1992;85:1440-1446.
20.
Van Boven AJ, Jukema W, Zwinderman AH, Crijns HJGM, Lie
KI, Bruschke AVG, REGRESS Study Group. Reduction of transient
myocardial ischemia with pravastatin in addition to
the conventional treatment in patients with angina pectoris.
Circulation. 1996;94:1503-1505.
21. Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383-1389. [Medline] [Order article via Infotrieve]
22.
Sacks FM, Pfeffer MA, Moye LA, Rouleau JL,
Rutherford JD, Cole TG, Brown L, Warnica JW, Arnold JMO, Chuan-Ghuan W,
Davis BR, Braunwald E, CARE Investigators. The effect of
prava-statin on coronary events after myocardial infarction
in patients with average cholesterol levels. N
Engl J Med. 1996;335:1001-1009.
23.
The Post Coronary Artery Bypass Graft Trial
Investigators. The effect of aggressive lowering of low-density
lipoprotein cholesterol levels and low-dose anticoagulation
on obstructive changes in saphenous-vein coronary artery bypass
grafts. N Engl J Med. 1997;336:153-162.
This article has been cited by other articles:
 |
|
 |
|
  M. Dweck, I. W Campbell, D. Miller, and C M. Francis Clinical aspects of silent myocardial ischaemia: with particular reference to diabetes mellitus The British Journal of Diabetes & Vascular Disease, May 1, 2009; 9(3): 110 - 116. [Abstract] [PDF]
|
|
|
|
 |
|
 P. A.L. Tonino, B. De Bruyne, N. H.J. Pijls, U. Siebert, F. Ikeno, M. van `t Veer, V. Klauss, G. Manoharan, T. Engstrom, K. G. Oldroyd, et al. Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention N. Engl. J. Med., January 15, 2009; 360(3): 213 - 224. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Di Mario, G. R. Heyndrickx, F. Prati, and N. H.J. Pijls CHAPTER 8 Invasive Imaging and Haemodynamics ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Crea, P. G. Camici, R. De Caterina, and G. A. Lanza CHAPTER 17 Chronic Ischaemic Heart Disease ESC Textbook of Cardiovascular Medicine, January 1, 2009; 2(1): med-9780199566990-chapter - med-9780199566990-chapter. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. A. Diamond and S. Kaul The Disconnect Between Practice Guidelines and Clinical Practice--Stressed Out JAMA, October 15, 2008; 300(15): 1817 - 1819. [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Katritsis and B. Meier Percutaneous Coronary Intervention for Stable Coronary Artery Disease J. Am. Coll. Cardiol., September 9, 2008; 52(11): 889 - 893. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Schomig, J. Mehilli, A. de Waha, M. Seyfarth, J. Pache, and A. Kastrati A Meta-Analysis of 17 Randomized Trials of a Percutaneous Coronary Intervention-Based Strategy in Patients With Stable Coronary Artery Disease J. Am. Coll. Cardiol., September 9, 2008; 52(11): 894 - 904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. K. Gehi, S. Ali, B. Na, N. B. Schiller, and M. A. Whooley Inducible Ischemia and the Risk of Recurrent Cardiovascular Events in Outpatients With Stable Coronary Heart Disease: The Heart and Soul Study Arch Intern Med, July 14, 2008; 168(13): 1423 - 1428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Holmes Jr, B. J. Gersh, P. Whitlow, S. B. King III, and J. T. Dove Percutaneous coronary intervention for chronic stable angina a reassessment. J. Am. Coll. Cardiol. Intv., February 1, 2008; 1(1): 34 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Brown, T. M. Sundt III, and B. J. Gersh Indications for Revascularization Card. Surg. Adult, January 1, 2008; 3(2008): 551 - 572. [Full Text]
|
|
|
|
|
|
T. D. Henry, C. L. Grines, M. W. Watkins, N. Dib, G. Barbeau, R. Moreadith, T. Andrasfay, and R. L. Engler Effects of Ad5FGF-4 in Patients With Angina: An Analysis of Pooled Data From the AGENT-3 and AGENT-4 Trials J. Am. Coll. Cardiol., September 11, 2007; 50(11): 1038 - 1046. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Erne, A. W. Schoenenberger, M. Zuber, D. Burckhardt, W. Kiowski, P. Dubach, T. Resink, and M. Pfisterer Effects of anti-ischaemic drug therapy in silent myocardial ischaemia type I: the Swiss Interventional Study on Silent Ischaemia type I (SWISSI I): a randomized, controlled pilot study Eur. Heart J., September 1, 2007; 28(17): 2110 - 2117. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. F. Cohn A new look at benefits of drug therapy in silent myocardial ischaemia Eur. Heart J., September 1, 2007; 28(17): 2053 - 2054. [Full Text] [PDF]
|
|
|
|
|
|
D. G. Katritsis, J. P.A. Ioannidis, T. P. Wharton Jr., V. A. Umans, H. O. Peels, A. P. Shah, D. M. Shavelle, W. J. French, S. De Servi, H. Kiat, et al. PCI for Stable Coronary Disease N. Engl. J. Med., July 26, 2007; 357(4): 414 - 418. [Full Text] [PDF]
|
|
|
|
|
|
N. H.J. Pijls, P. van Schaardenburgh, G. Manoharan, E. Boersma, J.-W. Bech, M. van't Veer, F. Bar, J. Hoorntje, J. Koolen, W. Wijns, et al. Percutaneous Coronary Intervention of Functionally Nonsignificant Stenosis: 5-Year Follow-Up of the DEFER Study J. Am. Coll. Cardiol., May 29, 2007; 49(21): 2105 - 2111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Erne, A. W. Schoenenberger, D. Burckhardt, M. Zuber, W. Kiowski, P. T. Buser, P. Dubach, T. J. Resink, and M. Pfisterer Effects of Percutaneous Coronary Interventions in Silent Ischemia After Myocardial Infarction: The SWISSI II Randomized Controlled Trial JAMA, May 9, 2007; 297(18): 1985 - 1991. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Radauceanu, F. Moulin, W. Djaballah, P. Y. Marie, F. Alla, B. Dousset, J. M. Virion, J. Capiaumont, G. Karcher, E. Aliot, et al. Residual stress ischaemia is associated with blood markers of myocardial structural remodelling Eur J Heart Fail, April 1, 2007; 9(4): 370 - 376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P Taggart Coronary revascularisation BMJ, March 24, 2007; 334(7594): 593 - 594. [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members, K. Fox, M. A. A. Garcia, D. Ardissino, P. Buszman, P. G. Camici, F. Crea, C. Daly, G. De Backer, P. Hjemdahl, et al. Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology Eur. Heart J., June 1, 2006; 27(11): 1341 - 1381. [Full Text] [PDF]
|
|
|
|
|
|
A. Berger, K.-J. Botman, P. A. MacCarthy, W. Wijns, J. Bartunek, G. R. Heyndrickx, N. H.J. Pijls, and B. De Bruyne Long-Term Clinical Outcome After Fractional Flow Reserve-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease J. Am. Coll. Cardiol., August 2, 2005; 46(3): 438 - 442. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Katritsis and J. P.A. Ioannidis Percutaneous Coronary Intervention Versus Conservative Therapy in Nonacute Coronary Artery Disease: A Meta-Analysis Circulation, June 7, 2005; 111(22): 2906 - 2912. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. L. Brown, L. D. Lisabeth, C. Roychoudhury, Y. Ye, and L. B. Morgenstern Recurrent Stroke Risk Is Higher Than Cardiac Event Risk After Initial Stroke/Transient Ischemic Attack Stroke, June 1, 2005; 36(6): 1285 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members, S. Silber, P. Albertsson, F. F. Aviles, P. G. Camici, A. Colombo, C. Hamm, E. Jorgensen, J. Marco, J.-E. Nordrehaug, et al. Guidelines for Percutaneous Coronary Interventions: The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology Eur. Heart J., April 2, 2005; 26(8): 804 - 847. [Full Text] [PDF]
|
|
|
|
|
|
N. H.J. Pijls The interventionalist's dilemma: innocent intimal hyperplasia or in-stent restenosis? Eur. Heart J., November 2, 2004; 25(22): 1970 - 1971. [Full Text] [PDF]
|
|
|
|
 |
|
 U. Thadani Current Medical Management of Chronic Stable Angina Journal of Cardiovascular Pharmacology and Therapeutics, March 1, 2004; 9(1_suppl): S11 - S29. [Abstract] [PDF]
|
|
|
|
|
|
F. Eefting, H. Nathoe, D. van Dijk, E. Jansen, J. Lahpor, P. Stella, W. Suyker, J. Diephuis, H. Suryapranata, S. Ernst, et al. Randomized Comparison Between Stenting and Off-Pump Bypass Surgery in Patients Referred for Angioplasty Circulation, December 9, 2003; 108(23): 2870 - 2876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Rihal, D. L. Raco, B. J. Gersh, and S. Yusuf Indications for Coronary Artery Bypass Surgery and Percutaneous Coronary Intervention in Chronic Stable Angina: Review of the Evidence and Methodological Considerations Circulation, November 18, 2003; 108(20): 2439 - 2445. [Full Text] [PDF]
|
|
|
|
|
|
R. A. Henderson, S. J. Pocock, T. C. Clayton, R. Knight, K. A. A. Fox, D. G. Julian, D. A. Chamberlain, and Second Randomized Intervention Treatment of Angina Seven-year outcome in the RITA-2 trial: coronary angioplasty versus medical therapy J. Am. Coll. Cardiol., October 1, 2003; 42(7): 1161 - 1170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. F. Cohn, K. M. Fox, and C. Daly Silent Myocardial Ischemia Circulation, September 9, 2003; 108(10): 1263 - 1277. [Full Text] [PDF]
|
|
|
|
|
|
R. J. Adams, M. I. Chimowitz, J. S. Alpert, I. A. Awad, M. D. Cerqueria, P. Fayad, and K. A. Taubert Coronary Risk Evaluation in Patients With Transient Ischemic Attack and Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the Stroke Council and the Council on Clinical Cardiology of the American Heart Association/American Stroke Association Circulation, September 9, 2003; 108(10): 1278 - 1290. [Full Text] [PDF]
|
|
|
|
|
|
R. J. Adams, M. I. Chimowitz, J. S. Alpert, I. A. Awad, M. D. Cerqueria, P. Fayad, and K. A. Taubert Coronary Risk Evaluation in Patients With Transient Ischemic Attack and Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the Stroke Council and the Council on Clinical Cardiology of the American Heart Association/American Stroke Association Stroke, September 1, 2003; 34(9): 2310 - 2322. [Full Text] [PDF]
|
|
|
|
|
|
G. Landesberg, M. Mosseri, Y. G. Wolf, M. Bocher, A. Basevitch, E. Rudis, U. Izhar, H. Anner, C. Weissman, and Y. Berlatzky Preoperative Thallium Scanning, Selective Coronary Revascularization, and Long-Term Survival After Major Vascular Surgery Circulation, July 15, 2003; 108(2): 177 - 183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Nathoe, D. van Dijk, E. W.L. Jansen, W. J.L. Suyker, J. C. Diephuis, W.-J. van Boven, A. B. de la Riviere, C. Borst, C. J. Kalkman, D. E. Grobbee, et al. A Comparison of On-Pump and Off-Pump Coronary Bypass Surgery in Low-Risk Patients N. Engl. J. Med., January 30, 2003; 348(5): 394 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Gibbons, J. Abrams, K. Chatterjee, J. Daley, P. C. Deedwania, J. S. Douglas, T. B. Ferguson Jr, S. D. Fihn, T. D. Fraker Jr, J. M. Gardin, et al. ACC/AHA 2002 Guideline Update for the Management of Patients With Chronic Stable Angina--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 Chronic Stable Angina) Circulation, January 7, 2003; 107(1): 149 - 158. [Full Text] [PDF]
|
|
|
|
|
|
Committee Members, R. J. Gibbons, J. Abrams, K. Chatterjee, J. Daley, P. C. Deedwania, J. S. Douglas, T. B. Ferguson Jr, S. D. Fihn, T. D. Fraker Jr, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--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 Chronic Stable Angina) J. Am. Coll. Cardiol., January 1, 2003; 41(1): 159 - 168. [Full Text] [PDF]
|
|
|
|
|
|
T. M. Sundt III, B. J. Gersh, and H. C. Smith Indications for Coronary Revascularization Card. Surg. Adult, January 1, 2003; 2(2003): 541 - 559. [Full Text]
|
|
|
|
 |
|
 G. A. Modest Guidelines for the Management of Patients with Chronic Stable Angina Ann Intern Med, September 17, 2002; 137(6): 548 - 549. [Full Text] [PDF]
|
|
|
|
 |
|
 K. M. Detre and R. Holubkov Coronary Revascularization on Balance: Robert L. Frye Lecture Mayo Clin. Proc., January 1, 2002; 77(1): 72 - 82. [Abstract] [PDF]
|
|
|
|
|
|
P.F. Cohn The value of continuous ST segment monitoring in patients with unstable angina Eur. Heart J., November 1, 2001; 22(21): 1972 - 1973. [PDF]
|
|
|
|
|
|
G. A. Modest, K. K. Ray, P. J. Sheridan, K. H. Chan, D. A. Barr, A. Y. Khakoo, D. A. Rastegar, H. Hemingway, A. M. Crook, and A. D. Timmis Underuse of Coronary Revascularization Procedures N. Engl. J. Med., July 26, 2001; 345(4): 294 - 296. [Full Text] [PDF]
|
|
|
|
|
|
C.V Patil, E Nikolsky, M Boulos, E Grenadier, and R Beyar Multivessel coronary artery disease: current revascularization strategies Eur. Heart J., July 2, 2001; 22(14): 1183 - 1197. [PDF]
|
|
|
|
|
|
S. C. Smith Jr, J. T. Dove, A. K. Jacobs, J. Ward Kennedy, D. Kereiakes, M. J. Kern, R. E. Kuntz, J. J. Popma, H. V. Schaff, D. O. Williams, et al. ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines): A report of the American College of Cardiology/ American Heart Association Task Force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) endorsed by the Society for Cardiac Angiography and Interventions J. Am. Coll. Cardiol., June 15, 2001; 37(8): 2239 - 2239. [Full Text] [PDF]
|
|
|
|
|
|
G. Landesberg, M. Mosseri, D. Zahger, Y. Wolf, M. Perouansky, H. Anner, B. Drenger, Y. Hasin, Y. Berlatzky, and C. Weissman Myocardial infarction after vascular surgery: the role of prolonged, stress-induced, ST depression-type ischemia J. Am. Coll. Cardiol., June 1, 2001; 37(7): 1839 - 1845. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. T. Bloomgarden American Diabetes Association 60th Scientific Sessions, 2000: Cardiovascular disease in diabetes Diabetes Care, February 1, 2001; 24(2): 399 - 404. [Full Text]
|
|
|
|
|
|
R. S. Blumenthal, G. Cohn, and S. P. Schulman Medical therapy versus coronary angioplasty in stable coronary artery disease: a critical review of the literature J. Am. Coll. Cardiol., September 1, 2000; 36(3): 668 - 673. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Gibbons, K. Chatterjee, J. Daley, J. S. Douglas, S. D. Fihn, J. M. Gardin, M. A. Grunwald, D. Levy, B. W. Lytle, R. A. O'Rourke, et al. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Chronic Stable Angina) J. Am. Coll. Cardiol., June 1, 1999; 33(7): 2092 - 2197. [Full Text] [PDF]
|
|
|
|
|
|
P. J. Scanlon, D. P. Faxon, A.-M. Audet, B. Carabello, G. J. Dehmer, K. A. Eagle, R. D. Legako, D. F. Leon, J. A. Murray, S. E. Nissen, et al. ACC/AHA guidelines for coronary angiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Coronary Angiography) developed in collaboration with the Society for Cardiac Angiography and Interventions J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1756 - 1824. [Full Text] [PDF]
|
|
|
|
 |
|
 D. C. Levin, V. M. Rao, R. L. Bree, and H. L. Neiman Turf Battles in Radiology: How the Radiology Community Can Collectively Respond to the Challenge Radiology, May 1, 1999; 211(2): 301 - 305. [Full Text]
|
|
|
|
|
|
D. Hasdai, A. Lerman, D. E. Grill, C. S. Rihal, and D. R. Holmes Jr. Medical Therapy after Successful Percutaneous Coronary Revascularization Ann Intern Med, January 19, 1999; 130(2): 108 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ferrari, B.a. Schnell, G. S. Werner, and H. R. Figulla Safety of deferring angioplasty in patients with normal coronary flow velocity reserve J. Am. Coll. Cardiol., January 1, 1999; 33(1): 82 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Pepine and P. C. Deedwania How Do We Best Treat Patients With Ischemic Heart Disease? Circulation, November 10, 1998; 98(19): 1985 - 1986. [Full Text] [PDF]
|
|
|
|
 |
|
 M K RUTTER, S M MARSHALL, and J M McCOMB Coronary artery disease and diabetes Heart, December 1, 1997; 78(6): 527 - 529. [Full Text] [PDF]
|
|
|
|
 |
|
 Revascularization Best for Silent Ischemia Journal Watch Cardiology, May 19, 1997; 1997(519): 1 - 1. [Full Text]
|
|
|
|
 |
|
 REVASCULARIZATION IMPROVES OUTCOMES FOR SILENT ISCHEMIA Journal Watch (General), May 8, 1997; 1997(508): 2 - 2. [Full Text]
|
|
|
|
|
|
T. Killip Silent Myocardial Ischemia: Some Good News Circulation, April 15, 1997; 95(8): 1992 - 1993. [Full Text]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||