(Circulation. 2001;103:e41.)
© 2001 American Heart Association, Inc.
Meeting Highlights
Highlights of the 22nd Congress of the European Society of Cardiology
From St Luke’s Episcopal Hospital, Texas Heart Institute, and the University of Texas Medical School at Houston, Houston, Tex.
Correspondence to James J. Ferguson, MD, Cardiology Research, MC 1-191, Texas Heart Institute, PO Box 20345, Houston, TX 77225. E-mail jferguson{at}heart.thi.tmc.edu
The following studies were presented at the 22nd Congress of the European Society of Cardiology in Amsterdam, the Netherlands, August 26 to 30, 2000.
Acute Coronary Syndromes
GUSTO IV ACS (Global Use of Strategies To
Open Occluded arteries in Acute Coronary Syndromes)
Presenter:
Maarten Simoons, MD, Thoraxcentrum, Erasmus University, Rotterdam, the
Netherlands
The study: A multicenter, randomized trial of adjunctive abciximab (a glycoprotein IIb/IIIa antagonist) in patients with acute coronary syndromes in whom an invasive/interventional strategy was not planned. A total of 7800 patients with a history of at least 5 minutes of chest pain at rest and either a positive troponin test or at least 0.5 mm ST-segment depression were treated with aspirin and heparin (or the low-molecular-weight heparin dalteparin in a predefined subset of patients in Scandinavia, Switzerland, and some US centers) and were randomized to receive placebo, a bolus and 24-hour infusion of abciximab, or a bolus and 48-hour infusion of abciximab. The primary end point of the study was the composite incidence of death or myocardial infarction (MI) at 30 days.
The results: As per the prespecified protocol, only 1.4% of patients were referred for urgent revascularization in the first 48 hours after randomization. At 30 days, the incidence of death (placebo, 3.9%; 24-hour abciximab, 3.4%; and 48-hour abciximab, 4.2%), or death/MI (placebo, 8.0%; 24-hour abciximab, 8.2%; and 48-hour abciximab, 9.1%) were not significantly improved in either of the abciximab groups. Troponin status and the presence of documented ST-segment changes were predictors of worse outcomes, but did not identify a group of patients who prospectively benefited from abciximab. In the Scandinavian low-molecular-weight heparin subset, dalteparin provided an adequate alternative to unfractionated heparin, but it did not seem to convey significant incremental benefit.
Summary: In patients with acute coronary syndromes who are not going forward to percutaneous coronary intervention, a 24- or 48-hour infusion of abciximab provided no incremental clinical benefit, despite risk factors of positive troponins and/or documented ST-segment depression.
ASPECT (Anticoagulants in Secondary Prevention
of Events in Coronary Thrombosis)
Presenter:
Robert van Es, MD, Thoraxcentrum, Erasmus University, Rotterdam, the
Netherlands
The study: A multicenter, randomized, open-label trial comparing aspirin, warfarin, and combined aspirin plus warfarin in patients after acute coronary syndromes. A total of 993 patients at 60 clinical centers in the Netherlands were randomized to receive aspirin (80 mg/d), warfarin (international normalized ratio [INR] 3.0 to 4.0), or combination therapy (80 mg of aspirin and warfarin to INR 2.0 to 2.5). The primary end point of the study was the first occurrence of death, MI, or stroke.
The results: The trial was terminated prematurely because of slow recruitment; at the time of stopping the study, the mean follow-up was 1 year. The primary composite event rate was 9.2% with aspirin alone, 5.2% with warfarin alone, and 5.1% with combination therapy. Major bleeding was 0.9% with both aspirin alone and warfarin alone and 2.1% with combination therapy. Minor bleeding was 4.8%, 7.7%, and 15.0% in the 3 groups, respectively.
Summary: In patients recently hospitalized with acute coronary syndromes, therapy with either high-intensity warfarin (mean INR 3.2) or aspirin plus medium-intensity warfarin (INR 2.0 to 2.5) was more effective than aspirin alone in reducing subsequent clinical events. These results were achieved with an acceptable safety profile, although combination therapy did result in more frequent major and minor bleeding complications.
APRICOT 2 (Antithrombotics in the Prevention of
Reocclusion In COronary Thrombolysis)
Presenter: Marc
A. Brouwer, MD, University Hospital Nijmegen, the
Netherlands
The study: A
multicenter, randomized study comparing aspirin versus aspirin plus
warfarin in patients after acute MI. A total of 300 patients with
ST-segment elevation MI who were successfully treated with thrombolytic
therapy (with TIMI 3 flow at inclusion) were randomized to receive
either aspirin (80 mg/d, n=147) or aspirin plus medium-intensity
warfarin (target INR 2 to 3, n=153). Patients underwent follow-up
angiography at 3 months; the primary end point of the study was the
incidence of angiographic reocclusion (TIMI flow grade
2).
The results: Reocclusion was seen in 30% of the aspirin group and 18% of the aspirin plus warfarin group (P=0.02). Total occlusion (TIMI flow grade of 0 or 1) was noted in 19% of the aspirin group and 9% of the aspirin plus warfarin group. Event-free survival (no death, reinfarction, or revascularization) was 70% in the aspirin alone group compared with 83% in the aspirin plus warfarin group (P<0.01).
Summary: In patients who have had successful thrombolysis for acute MI, the combination of aspirin plus medium-intensity warfarin (INR 2 to 3) is associated with significantly better subsequent coronary patency and better event-free survival than aspirin alone.
LIMIT-AMI (LImitation of Myocardial Injury
following Thrombolysis in Acute Myocardial Infarction)
Presenter:
Kenneth Baran, MD, St. Paul Heart Clinic, St Paul,
Minnesota
The study: A randomized trial of a humanized Fab antibody fragment (rhuMab) directed against the CD18 leukocyte adhesion molecule in patients with acute MI. A total of 413 patients from 60 clinical centers in the United States and Canada with ST-segment elevation and symptoms within the last 12 hours were randomized to 1 of 2 doses of rhuMab or placebo; 391 patients were ultimately analyzable. The primary end point of the study was the corrected TIMI frame count.
The results: There was no significant effect of rhuMab on corrected TIMI frame count, infarct size, or ST-segment resolution. There were no infarct-related deaths in the study.
Summary: A humanized Fab fragment directed against CD18 provided no benefit in coronary flow, infarct size, or resolution of ischemia.
VINO (Validation of Immediate
angioplasty in Non–Q-wave myocardial infarction: an Open, randomized
multicenter study)
Presenters:
Rudolf 
pa
ek, MD, PhD, Prague, Czech Republic; Peter Widimsk
,
MD, DrSC
The study: A randomized trial comparing aggressive with conservative therapy in patients with non–Q-wave acute MI. A total of 131 patients with acute MI without ST-segment elevation were randomized to receive either aggressive therapy (immediate angiography with appropriate revascularization) or conservative therapy (angiography only for persistent, recurrent, or stress-induced ischemia despite maximal medical therapy). The primary end point of the study was the incidence of death or reinfarction.
The results: Primary angioplasty was feasible, and it was performed in 47% of patients in the aggressive management group. The incidence of death or re-MI at 6 months was 6% in the aggressive group and 22% in the conservative group (P<0.01). Six-month mortality was 3% in the aggressive group and 13% in the conservative group (P<0.05).
Summary: In patients with non-ST elevation acute MI, early angiography and intervention is associated with improved clinical outcomes.
NICE-3 (National Investigators
Collaborating on Enoxaparin)
Presenter:
James Ferguson, MD, Texas Heart Institute, St Luke’s Episcopal
Hospital, Houston, Texas
The study: A multicenter, nonrandomized, observational study of combined therapy with low-molecular-weight heparin plus a platelet glycoprotein (GP) IIb/IIIa antagonist in patients with acute coronary syndromes. A total of 661 patients were entered in the study, of whom 616 received enoxaparin (1 mg/kg SC BID) and 1 of the 3 commercially available GP IIb/IIIa antagonists (abciximab, eptifibatide, or tirofiban). Combination therapy was initiated, and it was continued if patients went on to percutaneous revascularization without the use of unfractionated heparin. Patients who underwent percutaneous coronary intervention >8 hours after the last subcutaneous enoxaparin dose received an additional intravenous bolus of enoxaparin (0.3 mg/kg IV); patients who underwent intervention <8 hours after the last dose received no additional therapy. The primary end point of the study was in-hospital non-CABG major bleeding. A historic control rate of 2.0% was estimated from prior studies of patients receiving a GP IIb/IIIa antagonist and unfractionated heparin.
The results: The overall in-hospital incidence of non-CABG major bleeding was 1.9% (0.7% with abciximab, 3.2% with eptifibatide, and 1.4% with tirofiban). The overall incidence of clinical events with combination therapy was 0.3% for death, 3.4% for MI, and 2.1% for urgent target vessel revascularization. The overall incidence of thrombocytopenia (platelet count <100 000) was 0.9% with combination therapy.
Summary: The combination of enoxaparin and an intravenous GP IIb/IIIa antagonist does not seem to increase the incidence of non-CABG major bleeding over that of heparin plus a GP IIb/IIIa antagonist. It does seem to be safe and feasible to bring patients on combination therapy forward to the catheterization laboratory, without the use of unfractionated heparin.
COHORT Registry (Swedish National Register of
Cardiac Intensive Care)
Presenters: Ulf
Stenestrand, MD, Linkoping, Sweden; Lars Wallentin, MD, Uppsala,
Sweden
The study: A
nonrandomized, observational examination of the effect of early
revascularization and early initiation of statin therapy on mortality
after acute MI in 73 institutions in Sweden. The cooperative study
encompassed 
90% of Swedish coronary care units and followed
patients for at least 1 year after discharge. To qualify, this had to
be the first admission with a diagnosis of acute MI, and the patient
had to survive at least 14 days after admission. The use or nonuse of
statins and intervention was at the discretion of the treating
physician. The relative risk (RR) in patients with or without the
tested treatments was evaluated by Cox regression analysis that
adjusted for >30 covariates.
The results: Of 22 683 evaluable patients, 15 835 were not on a statin, and 6273 were. Clinically, statin patients tended to be younger (27.5% were >70 years versus 50.5% in the nonstatin group). Patients receiving statins had a significantly lower 1-year mortality (RR, 0.66; 95% CI, 0.55 to 0.99; P<0.001). In addition, 2436 patients underwent revascularization, and 20 626 did not. Again, patients undergoing revascularization tended to be younger (34% were >70 years versus 45.7% of nonrevascularized patients). One-year mortality was also significantly lower in the revascularized group (RR, 0.64; 95% CI, 0.42 to 0.71; P<0.001). Combining therapies had a synergistic effect (RR for statin plus revascularization, 0.36; 95% CI, 0.21 to 0.64, P<0.001).
Summary: In addition to other standard therapies, the early use of statins and early revascularization in patients after MI may have major synergistic effects on 1-year survival.
Congestive Heart Failure
COPERNICUS (CarvedilOl ProspEctive RaNdomIzed
CUmulative Survival)
Presenter:
Milton Packer, MD, Columbia-Presbyterian Medical Center, New York,
NY
The study: A multicenter, randomized trial of carvedilol in patients with severe congestive heart failure (CHF), both ischemic and nonischemic. A total of 2289 patients with severe CHF, an ejection fraction <25%, and symptoms at rest were randomized to receive either carvedilol (n=1156) or placebo (n=1133). Patients on intravenous vasodilators or inotropes were excluded, but hospitalized patients who were not in the intensive care unit could be included. Carvedilol therapy was begun at 3.125 mg BID and gradually increased up to 25 mg BID. The primary end point of the study was all-cause mortality. The study was powered to detect a difference in outcome after 900 deaths. The study was stopped prematurely in March 2000 on the advice of the Data Safety and Monitoring Board because of significant excess benefit in the carvedilol group.
The results: All-cause mortality was 18.5% in the placebo group and 11.4% in the carvedilol group (RR, 0.65; 95% CI, 0.51 to 0.81; adjusted P=0.0014). The mortality curves seemed to separate after 3 to 4 months and continued to diverge over the duration of follow-up. There was broad benefit across all major clinical subgroups (age, sex, ejection fraction, and ischemic/nonischemic cause). No subgroups of patients were noted that had CHF that was too severe to benefit from carvedilol therapy. It was estimated that if 1000 patients with severe CHF were treated for 3 years, carvedilol therapy would be associated with 200 fewer deaths.
Summary: In patients with severe CHF, long-term therapy with carvedilol is associated with a significant decrease in all-cause mortality. This benefit extends to all major subgroups, and no group of patients could be identified who had disease too severe to benefit.
MUSTIC (Multisite STimulation In
Cardiomyopathy)
Presenter: J.
Claude Daubert, MD, Center Hospitalier Universitaire, Rennes,
France
The study: A randomized, single-blind, crossover study of the safety and efficacy of biventricular pacing in patients with congestive heart failure (CHF). A total of 131 patients with class III CHF (>1 month), an ejection fraction <35%, a left ventricular end-diastolic diameter >60 mm, impaired functional status on a 6-minute walk test, and a significant ventricular conduction delay were randomized to receive biventricular pacing or not. Two groups of patients were included: 1 group had stable sinus rhythm and no indication for pacing (n=67) and 1 group otherwise required pacing for chronic atrial fibrillation with a slow ventricular response. In the first group, patients were randomized to biventricular pacing or no pacing for 3 months, then crossed over for 3 months to the other mode. In the second group, patients were randomized to biventricular pacing or single-chamber pacing and crossed over in the same fashion. The primary end point of the study was the 6-minute walk distance achieved while on therapy. The study was powered to detect a 10% difference in the primary end point.
The results: In
patients with sinus rhythm, the use of biventricular pacing was
associated with a significant improvement in 6-minute walk distance of
23% (P=0.0001), a
significant 32% relative improvement in quality of life scores
(P=0.0001), and a reduction in
the need for subsequent hospitalization. In contrast, in patients who
otherwise required ventricular pacing, there were no significant
differences between pacing modes in 6-minute walk distance,
O2,
quality of life scores, or subsequent hospitalization. However, when 2
patients with inadequate biventricular therapy were excluded
retrospectively, significant differences emerged. Patients in both
sinus rhythm and in the pacing-dependent group expressed a strong
preference for the active biventricular pacing mode.
Summary: In patients with class III heart failure and sinus rhythm, biventricular pacing significantly improves exercise tolerance. In similar patients who otherwise require pacing therapy, biventricular pacing, if properly applied, may result in similar benefits.
Atherosclerosis/Prevention
EUROASPIRE II (EUROpean Action on Secondary
Prevention by Intervention to Reduce Events)
Presenter:
David Wood, MD, National Heart and Lung Institute, London,
UK
The study: A survey
conducted in 5556 coronary patients in 15 countries in Europe from 1999
to 2000 that was aimed at describing the contemporary practice of
preventive cardiology and adherence to the 1998 Joint European
Societies recommendations on Coronary Prevention in Clinical Practice
(a prior survey, EUROASPIRE I, was conducted in 1995/1996 in 9
countries). Qualifying patients were hospitalized for CABG, PTCA, acute
MI, or angina and were interviewed 17 months after their
hospitalization.
The results: When
the results of the original 9 countries who participated in EUROASPIRE
I were compared with the results of EUROASPIRE II in the same
countries, the incidence of smoking was 21%, which was similar to that
the prior survey; 81% of patients were overweight (body mass index
>25 kg/m2), and 33% were obese (body mass
index >30 kg/m2, up from prior survey). The
proportion of patients achieving a target blood pressure <140/90
mm Hg was still only 50%, and 25% of patients still had blood
pressures >160/95 mm Hg. In contrast, more patients in the recent
survey (41% versus 33%) had achieved a cholesterol goal of <5.0
mmol/L, although more than half of the patients had still not reached
this goal. Aspirin (or other antiplatelet agent) use was high (84%),
and there was more frequent use of ß-blockers (66% versus 54%
previously) and ACE inhibitors (43% versus 29% previously). A
dramatic increase in lipid-lowering therapy (principally statins) was
also noted (63% versus 32% previously). However, considerable
country-to-country variation still existed in the use of these
therapies.
Summary: There is significant room to improve cardiovascular care, both from a lifestyle perspective (smoking, obesity, etc) and from a therapy perspective. Despite the more frequent use of pharmacological therapies, the majority of patients have still not met the blood pressure and cholesterol goals set by the Joint European Societies recommendations on coronary prevention.
ASAP (effects of Atorvastatin and
Simvastatin on Atherosclerosis Prevention in patients with
familial hypercholesterolemia)
Presenter:
Tineke Smilde, MD, UMC Nijmegen, Nijmegen, the Netherlands
The study: A randomized trial conducted at 2 clinical centers in the Netherlands comparing aggressive with conventional management of familial hypercholesterolemia. The study randomized 325 patients with familial hypercholesterolemia to receive either 80 mg of atorvastatin (aggressive treatment) or 40 mg of simvastatin (conventional treatment). Therapy was continued for 2 years. The primary end point of the study was intimal-medial carotid thickness (IMT) on duplex ultrasonography.
The results: Total cholesterol, triglycerides, and LDL decreased more with aggressive therapy. There was an associated regression in IMT in the aggressive therapy group, whereas IMT increased in the conventional therapy group. There were no differences in adverse clinical events between groups. Sex and smoking did not seem to contribute to changes in IMT.
Summary: In patients with familial hypercholesterolemia, aggressive lipid-lowering therapy is associated with significant improvements in IMT.
Interventional Cardiology
ADVANCE (Additional Value of Stents for
Treatment of Long Coronary Lesions)
Presenter:
Patrick Serruys, MD, PhD, Thoraxcentrum, Rotterdam, the
Netherlands
The study: A multicenter (40 sites in 14 countries), randomized trial comparing stenting and balloon angioplasty for long lesions. A total of 437 patients with lesions >20 mm in native vessels were treated with balloon angioplasty, and 149 patients were crossed over to stenting (bailout) because of a persistent significant obstruction (>50%), significant dissection, or impaired distal flow. The remaining 288 patients were randomized to stenting (NIR stent) or no additional therapy. The primary end point was major adverse cardiac events (death, MI, ischemia-driven target vessel revascularization) at 9 months. The study was originally designed to include 500 randomized patients, but it was discontinued prematurely on the basis of futility because of lack of benefit.
The results: The median total treated lesion length was 32 mm; 1 stent was used in 81% of cases. The incidence of major adverse cardiac events was 20.4% in the balloon angioplasty group (n=142), and 20.5% in the stent alone group (n=146); the incidence of major adverse cardiac events in the bailout cohort was 22.8%. The binary angiographic restenosis rate was significantly higher in the balloon angioplasty alone group (42% versus 27% with stents); however, most of the initial gain in the stent group was lost at follow-up. The bailout cohort was not followed angiographically.
Summary: More than a third of patients treated with balloon angioplasty for long lesions may require bailout stenting. In patients with long lesions, the clinical outcome of balloon angioplasty alone was better than expected, and additional stenting provided no incremental benefit in reducing the incidence of major adverse cardiac events.
VESPA (Verapamil high-dose Early administration
Slow release for Prevention of major cardiovascular events and
restenosis after Angioplasty)
Presenter:
Hans-Peter Bestehorn, MD, Cathlab Herz-Zentrum Bad Krozingen,
Bad Krozingen, Germany
The study: A randomized, multicenter, placebo-controlled trial of a calcium-channel blocker (high-dose slow-release verapamil) for the prevention of restenosis. A total of 700 patients undergoing percutaneous coronary intervention (including stenting in 83% of the patients) of native vessels were randomized to SR verapamil (480 mg per day) or placebo for 6 months. All patients received adjunctive aspirin and ticlopidine/clopidogrel. Follow-up angiography was performed at 6 months. The 2 primary end points were the number of patients with major cardiovascular events and the change in mean lumen diameter at follow-up.
The results: Clinical follow-up was available in 664 patients (94.9%), and follow-up angiography was available for 656 patients (93.7%). The use of stents varied from 65% to 91% at the participating institutions (average, 83%; not different between the treatment arms). There was a slight but nonsignificant trend favoring lower late lumen loss (the angiographic primary end point) in the verapamil group (0.74 versus 0.81 mm with placebo; P=0.11). Binary restenosis rates also were slightly, but not significantly, lower in the verapamil group (25.5% versus 32.2% with placebo; P=0.07). The number of patients with major cardiovascular events (death, MI, revascularization, and hospitalization because of angina; clinical primary end point) was significantly lower in the verapamil group (29.1% versus 37.6% with placebo; P=0.02).
Summary: In patients undergoing percutaneous coronary intervention of native vessels, adjunctive slow-release verapamil did not significantly reduce angiographic stenosis. Patients treated with verapamil did have fewer cardiovascular events at follow-up; the majority of these events (revascularization) arose as a consequence of follow-up angiography.
BetaACE Stent
Presenter:
Flavio Ribichini, MD, Sa Croce de Cervasca, Italy
The study: A randomized trial evaluating the efficacy and feasibility of adjunctive radiation therapy in patients with high plasma ACE levels (>34 IU/L) and a DD or ID genotype. A total of 66 patients undergoing stent implantation of de novo lesions were included in the study and were randomized to adjunctive radiation therapy (16–20 Gy of ß-radiation delivered by a 90Y source) or no adjunctive therapy. The primary end point of the study was angiographic mean lumen diameter at 6 months.
The results: Binary restenosis rates at 6 months were 37.5% in the control group and 17.9% in the radiation group (P=0.08). Follow-up mean lumen diameters (distribution frequency) were significantly lower (P=0.04) in the radiation group. Target vessel revascularization was also significantly lower in the radiation group (13% versus 35% in the control group; P=0.04).
Summary: Adjunctive ß-radiation therapy appeared to reduce restenosis in this small group of stent patients with high plasma ACE and a DD or DI ACE genotype. This study represents one of the first clinical trials in which such genetic screening might be used to stratify therapy.
DANSTENT ACE Genotype
Substudy
Presenter:
Henning Kelbaek, MD, Rigshospitalet, Copenhagen, Denmark
The study: A substudy of DANSTENT (evaluating restenosis in stented patients) examining whether ACE genotype, specifically D/I polymorphism, is predictive of restenosis. A total of 369 patients from DANSTENT were identified in whom ACE genotyping was performed. Six-month follow-up angiography and qualitative coronary angiography data were reviewed.
The results: There were 105 patients with the D/D genotype, 196 with the D/I genotype, and 68 with the I/I genotype. There were no significant differences between groups at follow-up in diameter stenosis, binary restenosis, revascularization, or mean lumen diameter distribution. Lesion length, postprocedure mean lumen diameter, and diabetes were multivariate predictors of restenosis; ACE genotype was not. D/D patients on ACE-inhibitor therapy were noted to have a high rate of restenosis.
Summary: In this series of patients with ischemic coronary artery disease undergoing stent implantation, ACE genotype did not identify patients at risk for restenosis. The potential interaction between D/D genotype, ACE-inhibitor therapy, and restenosis merits further investigation.
Hypertension
Calcium-Channel Blocker Meta-Analysis
Presenter: Curt
D. Furberg, MD, PhD, Wake Forest University, Salem, NC
The study: A meta-analysis of 9 randomized trials (n=27 743) of varying forms of first-line therapy in patients with hypertension. To be included, trials had to have >100 patients, compare calcium blockers with other forms of therapy, and include follow-up for >2 years. The various forms of therapy were classified as dihydropyridine calcium-channel blockers, nondihydropyridine channel blockers, and non-calcium channel blockers (including diuretics, ß-blockers, and ACE inhibitors). The meta-analysis looked specifically at outcome events of death, MI, CHF, stroke, or composite events.
The results: Patients treated with calcium-channel blockers had a significantly higher incidence of MI (odds ratio [OR], 1.26; 95% CI, 1.11 to 1.43; P=0.0003), congestive heart failure (OR, 1.25; 95% CI, 1.07 to 1.46; P<0.0005), and total major events (OR, 1.10; 95% CI, 1.02 to 1.18; P=0.018). There were no significant differences in stroke (OR, 0.90; 95% CI, 0.80 to 1.02) or all-cause mortality (OR, 1.03; 95% CI, 0.94 to 1.13).
Summary: Calcium-channel blockers may effectively lower blood pressure, but they are inferior to other forms of therapy because they have a higher incidence of MI, congestive heart failure, and total events. How calcium-channel blockers compare with individual first-line agents remains to be determined.
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||