Danish Multicenter Randomized Study of Invasive Versus Conservative Treatment in Patients With Inducible Ischemia After Thrombolysis in Acute Myocardial Infarction (DANAMI)
Background The aim of the DANish trial in Acute Myocardial Infarction (DANAMI) study was to compare an invasive strategy of percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass grafting (CABG) with a conservative strategy in patients with inducible myocardial ischemia who received thrombolytic treatment for a first acute myocardial infarction (AMI).
Methods and Results Of the 503 patients randomized to an invasive strategy, PTCA was performed in 266 (52.9%) and CABG in 147 (29.2%) from 2 to 10 weeks after the AMI. Of the 505 patients in the conservative treatment group, only 8 (1.6%) had been revascularized 2 months after the AMI. The patients were followed up from 1 to 4.5 years. The primary end points were mortality, reinfarction, and admission with unstable angina. At 2.4 years’ follow-up (median), mortality was 3.6% in the invasive treatment group and 4.4% in the conservative treatment group (not significant). Invasive treatment was associated with a lower incidence of AMI (5.6% versus 10.5%; P=.0038) and a lower incidence of admission for unstable angina (17.9% versus 29.5%; P<.00001). The percentages of patients with a primary end point were 15.4% and 29.5% at 1 year, 23.5% and 36.6% at 2 years, and 31.7% versus 44.0% at 4 years (P=<.00001) in the invasive and conservative treatment groups, respectively. At 12 months, stable angina pectoris was present in 21% of patients in the invasive treatment group and 43% in the conservative treatment group.
Conclusions Invasive treatment in post-AMI patients with inducible ischemia results in a reduction in the incidence of reinfarction, fewer admissions due to unstable angina, and lower prevalence of stable angina. We conclude that patients with inducible ischemia before discharge who have received treatment with thrombolytic drugs for their first AMI should be referred to coronary arteriography and revascularized accordingly.
Patients with AMI who are given thrombolytic therapy have improved survival at long-term follow-up compared with those treated with conventional therapy1 ; improved survival is particularly apparent in patients with sustained left ventricular function and a normal coronary flow.2 Yet thrombolytic treatment is not always followed by dissolution of the thrombus,3 4 and furthermore, many patients have a significant residual stenosis of the infarct-related vessel.4 Early studies5 also reported a higher incidence of postinfarction angina or recurrent ischemia in patients after thrombolytic therapy. Therefore, it has been postulated that revascularization would improve prognosis. However, PTCA immediately after thrombolysis did not result in a lower morbidity or mortality compared with conservative treatment or deferred PTCA.6 7
In patients with AMI, early reperfusion therapy may salvage part of the ischemic myocardium and thus limit infarct size and preserve left ventricular function. Subsequent revascularization procedures have no influence on infarct size but may improve healing of the infarct and thus prevent left ventricular remodeling. In patients with documented postinfarction myocardial ischemia, revascularization may alleviate such ischemia, which might reduce the incidence of future coronary events, in accordance with studies of invasive treatment in patients with stable angina pectoris or silent ischemia.8 9 10 Previously, other studies comparing an early invasive versus noninvasive therapy did not show a difference in outcome.11 12 13 However, in those studies, only 56% to 61% of patients allocated to invasive strategy underwent such intervention. Furthermore, in the conservative treatment group, 5% to 20% also underwent intervention,11 12 13 and in the TIMI Study, all patients with ischemia were catheterized.11 Also, in one study, only PTCA and not CABG was used.13
The DANAMI study compared a deferred invasive strategy comprising either PTCA or CABG with a conservative strategy in patients with documented myocardial ischemia within the first weeks after an AMI. Patients with unstable angina who usually require intervention were excluded, as were patients without postinfarction ischemia. The primary end points consisted of death, AMI, and admission with unstable angina pectoris. Revascularization was scheduled within 2 to 5 weeks of discharge; follow-up was for ≥1 year.
Patients with suspected AMI admitted to any of the 43 participating hospitals in Denmark were screened for the study. Patients ≤69 years old were considered for the study only if they had a definite AMI, ie, significant elevation of creatine kinase–MB (ie, increase to at least twice the upper-normal limit), ST deviation or T changes and/or Q waves developed, and thrombolytic treatment was begun within 12 hours of the onset of symptoms.
Excluded were patients with previous AMI, PTCA, or bypass surgery; patients receiving less than half of the planned thrombolytic dose; patients requiring immediate invasive intervention, including drug-resistant unstable angina pectoris; patients experiencing a drop in systolic blood pressure during exercise; and patients with significant noncoronary disease, including significant renal failure or coagulopathy. Patients participating in other intervention studies, which was cause for expected incomplete follow-up, and patients judged unable to perform a symptom-limited bicycle exercise test, as well as those with ECG abnormalities precluding evaluation of the ST segment during exercise, ie, left bundle-branch block or pacemaker, were also excluded.
Definition of Postinfarction Ischemia
To be included in the study, patients had to demonstrate inducible postinfarction ischemia: either symptomatic angina pectoris presenting spontaneously >36 hours after admission or during a predischarge exercise test or ST changes during exercise compatible with ischemia, ie, ST depression ≥0.1 mV 0.08 seconds after J-point in any lead or ST elevation ≥2.0 mV 0.08 seconds after J-point in any lead without Q waves. On the basis of these definitions, three groups of patients with postinfarction ischemia were identified: (1) angina with documented ischemia, ie, patients fulfilling both criteria (type A); (2) angina without documented ischemia, ie, patients with angina but without ST changes during the exercise test (type B); and (3) silent ischemia, ie, patients with ST deviations during exercise but without angina during their stay in the hospital ward or during the exercise test (type C).
A symptom-limited bicycle exercise test was performed in all patients at discharge. An initial workload of 25 W was used, increased by 25 W every 2 minutes until the patient stopped owing to angina, dyspnea, fatigue, claudication, a fall in systolic blood pressure to 20 mm Hg below the preexercise resting value, or attainment of a target heart rate (defined as 200 minus the patient’s age). Medical treatment was not discontinued before the test. Patients with a drop in blood pressure during the exercise test were referred to coronary arteriography.
Patients with postinfarction ischemia who met the criteria and gave written consent were randomized by a telephone call to the coronary care unit at Rigshospitalet. Patients were prospectively stratified by age, sex, and type of ischemia, ie, type A, B or C (see above).
For the first year after randomization, all patients were seen in the hospital outpatient clinic for registration of follow-up data at 3, 6, and 12 months. Medical history, presence of symptoms, and signs of stable angina, unstable angina, heart failure, or AMI were registered. At the 3- and 12-month follow-up visits, a maximal symptom-limited exercise ECG was performed. Final follow-up data on admissions for unstable angina, reinfarction, and PTCA or bypass procedures were obtained from the national database and from hospital records (see below). Follow-up was from 1 to 4 years (median, 2.4 years).
Study End Points
The primary end points were the occurrence of death, reinfarction, or admission with unstable angina. For the combined end point, only the first occurrence of any of the end points was counted. Secondary end points included incidence of angina pectoris, severity of angina according to CCS classification, and consumption of anti-ischemic medication. The criterion for periprocedural AMI during PTCA was defined in the same manner as the index infarction. Perioperative AMI diagnosis required new Q waves of 0.04 seconds in at least two contiguous leads. The criteria for in-hospital reinfarction were the same as for the index infarction (see above). Out-of-hospital reinfarction was defined as development of new Q waves of ≥0.04 seconds in at least two contiguous leads. Unstable angina was defined as admission due to chest pain at rest after exclusion of AMI.
At follow-up, medical treatment was registered. For this presentation, calcium antagonists, β-blockers, and long-acting nitrates were considered as anti-ischemic medication. In both study arms, all patients were treated with 150 mg aspirin every day unless contraindicated (prescribed to 98% of patients).
In patients randomized to invasive therapy, a coronary arteriography was planned to be performed at one of the five invasive centers within 2 weeks of the exercise test. Coronary stenoses were considered significant if there was ≥50% reduction in the luminal diameter of any artery with a reference diameter ≥2 mm. Full revascularization was aimed for with PTCA or CABG.
PTCA was scheduled to be performed within 2 weeks of randomization in patients with either one- or two-vessel disease and a maximum of three significant stenoses or occlusion of the infarct-related artery. Conventional PTCA without stent implantation was performed. Success of PTCA was defined as >20% luminal diameter change and remaining stenoses <50% in all dilated vessels. CABG was scheduled to be performed within 5 weeks of randomization in all patients with left main stem stenosis, two-vessel disease with a total of more than three stenoses, three-vessel disease, and occlusion of a non–infarct-related artery. If PTCA was not successful, the patient was referred for CABG. Revascularization was not indicated in patients without significant stenoses or in whom CABG was not expected to be successful, eg, diffuse disease with poor runoff. Successful bypass operation was defined as complete revascularization as judged by the surgeon.
Medical treatment was prescribed according to local practice.
Medical treatment, including the choice of anti-ischemic medication, was prescribed according to local practice. Patients who developed severe angina pectoris, usually CCS classes 3 or 4, were referred to coronary arteriography at the discretion of the referring physician.
Data on medical history, treatment, and exercise test were collected on specially prepared forms at the referring hospital and data regarding invasive treatment at the invasive center. All data were prospectively entered into a central database.
Information on death and admissions was obtained from the National Board of Health and from follow-up examinations performed after 3, 6, and 12 months. All patients alive completed follow-up. In Denmark, patient data, including a discharge diagnosis, are reported to a county-based national database. If a cardiac-related discharge diagnosis was used, detailed information was obtained from the hospital charts in each case.
All deaths and admissions with a potential new AMI were independently assessed by a central data review committee. All ECGs from the follow-up examinations were QRS scored14 at the ECG core laboratory.
The recruitment of patients was not consecutive in all departments, and a log of all AMI admissions was not kept. To estimate the relative proportion of AMI patients randomized, all admissions due to suspected AMI were consecutively registered during ≈7 months in six hospitals in two counties representing a mixture of urban and rural population: Aarhus Amtssygehus, Skejby University Hospital, Hillerød, Frederikssund, Helsingør, and Hørsholm hospitals.
We intended to include 1000 patients in the study on the basis of an expected incidence of cardiac death or recurrent AMI of 20% with a 33% reduction in the invasive treatment group. This would give a power of 20% to detect a difference between the two treatment groups at α=5%.
Comparison of groups was performed by χ2 statistic, survival was analyzed by log-rank test, and survival curves were estimated according to Kaplan-Meier. All analyses were based on the intention-to-treat principle.
An independent audit with source verification was performed in 20% of all the patients and in 40% of all invasive data. There were no indications of fraud; discrepancies regarding primary end points were found in 1.5% of the data.
One thousand eight patients were included in the study from October 1990 to March 1994. Five hundred five patients were randomized to conservative treatment and 503 to invasive treatment. Streptokinase was given to 1003 patients, recombinant tissue plasminogen activator to 4, and anisoylated plasminogen streptokinase activator complex to 1. Baseline data showed no significant differences between the two groups (Table 1⇓). Mean age was 56.4 years in the conservative treatment group (range, 24 to 69 years) and 56.2 years (range, 32 to 69 years) in the invasive treatment group.
All 1008 patients underwent an exercise test. In each group, the median maximal work capacity was 125 W (Table 2⇓). The proportion and distribution of ST changes were similar. Most patients (54% to 56%) stopped exercise owing to fatigue, and only 15% to 16% stopped because of angina pectoris. The type of inducible ischemia was similar in the two groups. In each group, only 16% had no ST deviation at exercise ECG and 56% to 57% had silent ischemia.
Invasive Treatment Group
Table 3⇓ demonstrates the number of patients who had coronary arteriography (n=482), PTCA (n=266), and CABG performed (n=147). After coronary arteriography, no revascularization was planned in 46 patients (38 without significant coronary lesions, 8 miscellaneous). Twenty-five (5.2%) of 482 patients had a significant stenosis of the left main coronary artery, 236 (49%) had one-vessel disease, 94 (20%) had two-vessel disease, and 89 (18%) had three-vessel disease. The mean ejection fraction was 58%, with a first and third quartile of 49% and 65%, respectively. PTCA was planned in 275 and performed in 266 (52.9%) of 503 patients. CABG was planned in 162 and performed in 147 (29.2%) of 503 patients. Thus, revascularization was performed in 413 (82.1%) of the 503 patients randomized to invasive treatment, whereas 17.9% in the invasive treatment group received no revascularization. The median time to PTCA and CABG was 18 days (10th and 90th percentiles, 8 and 41 days) and 38 days (10th and 90th percentiles, 21 and 64 days) after randomization, respectively.
There were no major complications due to coronary arteriography. PTCA (266 patients) was complicated by 2 AMIs (0.8%), and 4 patients (1.5%) underwent acute CABG within 24 hours after PTCA to obtain complete revascularization. Another 8 patients (3.0%) were referred to elective CABG within 1 month. The success rate of PTCA was 95.5%. In the CABG group (147 patients), there were 2 perioperative AMIs (1.4%), 2 procedure-related deaths (1.4%), and 1 nonfatal stroke (0.7%). Complete revascularization was obtained in 85% of the patients treated with CABG. Of the invasive treatment group, 27 patients (5.4%) had a second procedure during the first year (PTCA [n=18] or CABG [n=9]).
Conservative Treatment Group
The anti-ischemic medical treatment at randomization and during follow-up is presented in Table 4⇓. Eight patients (1.6%) randomized to conservative therapy had PTCA (n=5) or CABG (n=3) performed during the first 2 months of follow-up, and 76 patients (15%) had PTCA (n=33) or CABG (n=43) during the first year due to unacceptable angina pectoris.
Primary End Points
Table 5⇓ and Figs 1 through 4⇓⇓⇓⇓ show the follow-up results for the primary end points. The percentages of patients with the combined primary end point were 15.4% and 29.5% at 1 year, 23.5% and 36.6% at 2 years, and 31.7% and 44.0% at 4 years (P<.00001) in the invasive and conservative treatment groups, respectively. No significant difference in mortality was seen. A highly significant reduction in the number of patients with reinfarction was seen in the invasive treatment group (P=.0038). The difference appeared a few weeks after randomization. In 11 patients (7 in the invasive treatment group and 4 in the conservative treatment group), the diagnosis was silent myocardial infarction. In addition, the number of patients admitted with unstable angina pectoris was significantly reduced in the invasive treatment group (P<.00001), which was apparent early during the follow-up.
Secondary End Points
Information about angina pectoris and anti-ischemic treatment during the first year was complete for all surviving patients. Severe angina pectoris (CCS class 3) was present in ≈2% and moderate angina (CCS class 2) in 6% to 8% in the invasive treatment group during the follow-up period, significantly differing from the conservative treatment group (Fig 5⇓). The number of patients in the conservative treatment group with angina class 2 or 3 declined from 23% at 3 months’ follow-up to 15% after 1 year (P=.001), whereas the percentage in class 1 remained almost constant (29% and 28%) (P=NS).
Table 4⇑ shows the change in anti-ischemic treatment. At the time of randomization, treatment was similar in the two groups. During the first year, significantly more anti-ischemic medication was prescribed in the conservative treatment group (P<.001). The anti-ischemic treatment was gradually decreased in the invasive treatment group during the entire period. In the conservative treatment group, treatment was increased at 3 months and remained almost constant the rest of the first year.
After 1 year, 17.4% of patients in the conservative treatment group and 15.6% in the invasive treatment group were receiving treatment with ACE inhibitors.
During the registration period, a total of 499 patients were admitted with AMI to the six hospitals selected. Three hundred ninety-eight patients had either a previous AMI, were >69 years of age, had symptoms for >12 hours, or did not receive thrombolytic treatment. Of the remaining 101 patients, 41 (41%) had inducible ischemia during admission as defined in the DANAMI protocol. Thus, 41 (8.2%) of 499 AMI patients fulfilled the DANAMI inclusion criteria.
DANAMI is the first study to show a significant benefit of revascularization in selected patients after AMI. In particular, the invasive strategy (PTCA and CABG) in patients with inducible ischemia after myocardial infarction was associated with a reduction in recurrent infarction and admissions for unstable angina as well as a reduction in prevalence and severity of angina.
Several randomized studies6 11 12 13 have compared an invasive strategy with a conservative strategy in AMI. None of those studies showed any benefit from invasive treatment, but there are several important differences between those studies and the DANAMI study.
When the intention-to-treat principle is used, it is of particular importance that the assigned treatment is actually given, otherwise a possible effect may be lost. The rate of revascularization in the invasive treatment group was 82.1% in the DANAMI study, much higher than in TIMI IIB (61%),11 SWIFT (58%),12 or the Israeli study (56%).13 Furthermore, very few patients in the conservative treatment group (1.6%) received revascularization at a time point when the revascularization procedures in the invasive treatment group had been completed (2 months after randomization). This is different from the above-mentioned studies in which between 5% and 20% of the patients in the conservative treatment group were revascularized before discharge. The DANAMI study was thus especially well suited to disclose any clinically significant difference between the two treatment strategies because almost all patients received the intended treatment, and there was a very low crossover rate from conservative to invasive treatment.
In the DANAMI study, only patients with postinfarction ischemia were included, and because the effect of revascularization is to relieve ischemia, this may account for the beneficial effect on the reinfarction rate. This is different from other studies in which patients were entered at an early stage, before exercise tests or ambulatory ECG monitoring15 could be performed, resulting in inclusion of patients without residual ischemia, in whom an effect of revascularization is less likely.
Deferred invasive treatment, as in our study, has the advantages that patients with residual ischemia can be selected and that PTCA and CABG can be performed safely.7 16 17 One-year mortality in the DANAMI study was 2% compared with 5.0% in the SWIFT study12 ; 6-week mortality in TIMI IIB was 4.7%11 in both the conservative and the invasive treatment groups. These studies, however, also included reinfarctions. One limitation of the DANAMI strategy is that early deaths due to reinfarctions will occur before they possibly can be prevented by invasive treatment. There was no reduction in late mortality; however, the curves began to separate. It is possible that long-term follow-up will show a survival benefit, as in the long-term follow-up of the early surgery–versus–medical therapy studies.8 9 The mortality rate in AMI patients with postinfarction ischemia was lower than expected18 but was in accordance with recent data from the GISSI-2 trial.19 During the planned longer follow-up time, the more frequent reinfarctions in the conservative treatment group may result in a higher mortality in this group.20
Invasive treatment was very effective in reducing the presence of angina pectoris even though anti-ischemic treatment was decreased during the same period. Only 8% of patients suffered angina pectoris CCS class 2 or more after 1 year. This is significantly different from the conservative treatment group, in which the anti-anginal treatment was increased after 3 months. The percentage of conservatively treated patients in CCS classes 2 and 3 decreased after 6 and 12 months, probably reflecting the number of patients being revascularized during this period (Fig 5⇑).
β-Blockers are known to reduce mortality after AMI. Only 40% of patients in the conservative treatment group received β-blockers; however, 23% were treated with calcium antagonists, mainly verapamil, which frequently was used as a secondary AMI prophylaxis because many of the centers had participated in the DAVIT-2 study.21 The use of cardioprotection after AMI was thus not very different from the practice in the United States today.22
It was estimated that the patients who were randomized accounted for 41% of those eligible but only for 8.2% of all patients admitted with AMI. It would be important to know if the results also apply to the excluded patients. Because revascularization in the elderly is safe and effective,23 it is likely that the results are also valid in older patients. If patients with recurrent AMI had been included, more patients with extensive disease would have been included and a positive effect of revascularization would seem even more likely.8 9 In patients who did not receive thrombolytic treatment, one would expect more patients to have occluded coronary arteries, but this would probably not impair the effect of the invasive treatment. Though it is not proven, we believe that the results of the DANAMI study probably apply to all AMI patients with recurrent ischemia.
We conclude that invasive treatment compared with conservative treatment in post-AMI patients with inducible ischemia results in a reduction in the incidence of reinfarction, fewer admissions due to unstable angina, lower prevalence and less severity of stable angina, and less anti-ischemic treatment. Even though the mortality rate was not changed at a median of 2.4 years of follow-up, the other effects were so pronounced that the clinical relevance is obvious. We suggest that AMI patients with inducible ischemia either during admission or during an exercise test before discharge be referred to coronary arteriography and revascularized accordingly.
Selected Abbreviations and Acronyms
|AMI||=||acute myocardial infarction|
|CABG||=||coronary artery bypass graft|
|CCS||=||Canadian Cardiovascular Society|
|DANAMI||=||DANish Trial in Acute Myocardial Infarction|
|PTCA||=||percutaneous transluminal coronary angioplasty|
Peer Grande (national coordinator), Rigshospitalet; Jan Kyst Madsen (national coordinator), Rigshospitalet; Per Thayssen, Odense University Hospital; Ulrik Eriksen, Skejby University Hospital; Kari Saunamäki, Rigshospitalet; Eli Kassis, Gentofte Amtssygehus; and Klaus Rasmussen, Aalborg Sygehus.
Stig Haunsø (chairman), Rigshospitalet; Torsten Toftegaard Nielsen, Skejby University Hospital; Torben Haghfelt, Odense University Hospital; and Per Fritz-Hansen, Gentofte Amtssygehus.
Erik Hjelms, Aalborg Sygehus; Peter Kildeberg Paulsen, Skejby University Hospital; Poul Alstrup, Aalborg Sygehus; Henrik Arendrup, Rigshospitalet; Uffe Niebuhr-Jørgensen, Gentofte Amtssygehus; Knud Høier-Madsen, Gentofte Amtssygehus; and Lars Ib Andersen, Odense University Hospital.
Rigshospitalet, Copenhagen (n=212 patients); Skejby University Hospital, Aarhus (n=111); Odense University Hospital, Odense (n=81); Gentofte Amtssygehus, Copenhagen (n=70); and Aalborg Sygehus, Aalborg (n=29).
Peter Clemmensen (Rigshospitalet, Copenhagen), Henning Rud Andersen (Skejby University Hospital, Aarhus), and Verner Rasmussen (Hvidovre Hospital, Copenhagen).
Per Kragh Andersen, MSc, Statistical Research Unit, University of Copenhagen, and Jørgen Granborg, MD, Copenhagen.
Odense University Hospital, Odense (n=74 patients) (Per Thayssen, Torben Haghfelt, Jens Brock Johansen, Claus Tveskov, Anders Bo Junker, Hans Mickley, Poul Erik Andersen, Per Justesen, and Lars Ib Andersen); Gentofte Amtssygehus, Copenhagen (n=70 patients) (Eli Kassis, Elsebeth Olsen, Uffe Niebuhr-Jørgensen, and Knud Høier-Madsen); Hvidovre Hospital, Copenhagen (n=67) (Flemming Pedersen, Gorm Jensen, Ib Christiansen, Jørgen Fischer Hansen, and Merete Vaage-Nilsen); Glostrup Amtssygehus, Copenhagen (n=60) (Jens Rokkedal Nielsen, Anette Sjøl, and Michael Ottesen); Rigshospitalet, University of Copenhagen, Copenhagen (n=60) (Peer Grande, Jan Kyst Madsen, Stig Haunsø, Kari Saunamäki, Rolf Steffensen, and Henrik Arendrup); Skejby University Hospital, Århus (n=46) (Torsten Toftegaard Nielsen, Ulrik Eriksen, Per Henningsen†, and Peter Kildeberg Paulsen); Bornholms Centralsygehus, Rønne (n=34) (Folmer Lynggaard and Inge Birkedal); Holstebro Centralsygehus, Holstebro (n=34) (Leif Hagerup); Aarhus Amtssygehus, Aarhus (n=33) (Kristian Thygesen, Else Vigholt, and Anne Thomassen); Hillerød Sygehus, Hillerød (n=33) (Arne Johannessen and Kresten Mellemgaard); Bispebjerg Hospital, Copenhagen (n=32) (Jørgen Videbæk, Hanne Halgreen, Andrea Landorph, Hanne Mollerup, and Vibeke Sørensen); Sygehuset õresund, Hørsholm (n=26) (Henrik Vagn-Nielsen and Peter Kaiser-Nielsen); Nykøbing Falster Centralsygehus, Nykøbing Falster (n=25) (Bjarne Sigurd, Helle Nielsen, and John Hilskov); Ringsted Sygehus, Ringsted (n=25) (Jens Erik Clausen, Kim Melbye, Jimmy Schultz, Peter Madsen, and Kern Olofsson); Svendborg Sygehus, Svendborg (n=25) (Torben Pindborg, Flemming Egede, Jon Rasmussen, and John Markenvard); Holbæk Centralsygehus, Holbæk (n=24) (Erling Birk Madsen, Mogens Westergaard, and Dan Hansen); Næstved Centralsygehus, Næstved (n=24) (Tage Lysbo Svendsen, Henrik Madsen, John Larsen, and Walther Nielsen); Haderslev Centralsygehus, Haderslev (n=23)(Kenneth Egstrup, Peter Bendixen, and Svend Eggert Jensen); Sygehuset Øresund, Helsingør (n=23) (Erik Agner and Jørgen Kanters); Randers Centralsygehus, Randers (n=22) (Preben Lomholt); Aalborg Sygehus, Aalborg (n=21) (Ebbe Steinmetz, Klaus Rasmussen, Jens Aarøe, Erik Hjelms, and Poul Alstrup); Herning Centralsygehus, Herning (n=19) (Ebbe Klarholt and Allan Johansen); Odder Centralsygehus, Odder (n=19) (Birthe Jastrup, Jens Herman Jensen, and Lars Faldborg); Vejle Sygehus, Vejle (n=19) (Mogens Tangø, Peter Johansen, Lone Vigh, Aage Deding, and Jan Svendsen); Viborg Sygehus, Viborg (n=17) (Ole Lederballe and Lis Krøll); Hjørring Sygehus, Hjørring (n=15) (Erik La Cour Petersen, Holger Sejersen, and Per Hyldgaard Jensen); Kjellerup Sygehus, Kjellerup (n=15) (Morten Scheibel); Silkeborg Centralsygehus, Silkeborg (n=15) (Frode Rømer and Tage Jensen); Frederikssund Sygehus, Frederikssund (n=13) (Poul Ebbe Nielsen, Mogens Bahnsen, and Allan McNair); Tønder Sygehus, Tønder (n=12) (Morten Brøns, Søren Lassen, Per Damkier Hansen, and Jørgen Andersen); Fredericia Sygehus, Fredericia (n=11) (Knud Nørregaard-Hansen and Lars Skadhauge); Nakskov Sygehus, Nakskov (n=11) (Jørn Badskjær and Tommy Budek); Nyborg Sygehus, Nyborg (n=11) (Ole Pedersen-Bjergaard); Slagelse Sygehus, Slagelse (n=9) (Per Eliasen); Hobro Sygehus, Hobro (n=8) (Henning Andersen and Poul-Anders Moustsen); Brønderslev Sygehus, Brønderslev (n=7) (Henning Kjeldsen); Herlev Amtssygehus, Copenhagen (n=6) (Jan Bech); Frederikshavn Sygehus, Frederikshavn (n=5) (Jens-Jørgen Kjærgaard); Fakse Amtssygehus, Fakse (n=4) (Klaus Kølendorf); Faaborg Sygehus, Faaborg (n=4) (Anne Grete Mikkelsen); Frederiksberg Hospital, Copenhagen (n=4) (Kjeld Lyngborg); Tarm Sygehus, Tarm (n=2) (Inge Helleberg); and Nykøbing Mors Centralsygehus, Nykøbing Mors (n=1) (Torben Glud and Peer Klose Frederiksen).
ECG Core Laboratory
Duke University Medical Center, Durham, NC.
Medical Department B, Rigshospitalet (Ingelise Lytzen, responsible secretary, and Hanne Hoegh).
The DANAMI Investigators acknowledge the invaluable support of The Danish Heart Foundation, which funded this study. We acknowledge Maarten Simoons, MD (The Netherlands), Galen Wagner, MD (United States), Douglas Chamberlain, MD (Great Britain), Koos Lubsen, MD (The Netherlands) and Robert Califf, MD (United States) for their help and advice. We also acknowledge the doctors and nurses who participated in the study.
- Received November 26, 1996.
- Revision received March 7, 1997.
- Accepted March 23, 1997.
- Copyright © 1997 by American Heart Association
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