Highlights of the 21st Congress of the European Society of Cardiology
The following studies were presented at the 21st Congress of the European Society of Cardiology, August 28–September 1, 1999, in Barcelona, Spain.
HOPE (Heart Outcomes Prevention Evaluation)
Presenters: Salim Yusuf, McMaster University, Hamilton, Ontario, Canada; Gilles Dagenais, University of Montreal, Montreal, Canada; Peter Sleight, University of Oxford, Oxford, UK; on behalf of the HOPE Investigators.
The study: A large-scale multicenter (267 hospitals in 19 countries), randomized, placebo-controlled trial of ACE-inhibitor therapy and vitamin E supplementation in patients at high risk for vascular events. Inclusion criteria included age >55 years and evidence of vascular disease (coronary heart disease, stroke, and peripheral vascular disease, or diabetes and 1 other cardiovascular risk factor). Patients with heart failure, a low ejection fraction, current ACE-inhibitor or vitamin E therapy, or acute events within the previous 4 weeks were excluded. A total of 9541 qualifying patients were randomized in a 2×2 factorial design to ramipril (up to 10 mg/d) or placebo and vitamin E (400 IU/d) or placebo and were followed up for 4 to 6 years. The primary end point of the study was the composite of cardiovascular death, myocardial infarction (MI), and stroke. Secondary end points included revascularization and the development of congestive heart failure (CHF), unstable angina, or complications of diabetes. The study was terminated at 4.5 years because of convincing benefit in the ramipril group.
The results: Vitamin E therapy was not associated with any significant clinical benefit. Composite primary outcome events occurred in 16% of the vitamin E group and 15.4% of the placebo group (P=NS). No specific clinical subgroups showed clinical benefit, and there were no benefits in any of the individual component end points or in any of the secondary outcome end points.
Conversely, ramipril therapy was associated with a highly significant clinical benefit. Composite primary outcome events occurred in 13.9% of the ramipril group and 17.5% of the placebo group (RR=0.78; P=0.000002). There was also significant benefit in the individual end points of cardiovascular death (6.0% versus 8.0%, RR=0.75, P=0.0002), MI (9.8% versus 12.0%, RR=0.80, P=0.0005), stroke (3.3% versus 4.8%, RR=0.68, P=0.0002), and total mortality (10.3% versus 12.2%, RR=0.83, P=0.0035). There were no differences between groups in noncardiovascular death (4.3% versus 4.2%, P=NS). From the perspective of the secondary end points, there was no effect of ramipril therapy on hospitalizations for unstable angina, but there was a trend toward fewer heart failure hospitalizations, and significantly fewer revascularizations were necessary (16.0% versus 18.4%, RR=0.85, P=0.0013). There was also striking benefit in patients with documented normal ejection fractions, with significant reductions in the primary outcome end point, cardiovascular death, MI, stroke, heart failure, and revascularization. In the overall population, the divergence of the primary end point was present in the first year, and the event curves continued to diverge through year 4. The clinical benefit was noted in all of the major subgroups, including patients with/without cerebrovascular disease, diabetes, hypertension, coronary artery disease, peripheral vascular disease, men/women, and young/old patients.
There was only a minor decrease in systolic (−3 mm Hg) and diastolic (−1.5 mm Hg) blood pressure. The investigators speculated that although there was a strong relationship between clinical events and systolic blood pressure (but not diastolic blood pressure), the benefits of ramipril therapy were chiefly due to a vascular protective effect rather than a blood pressure–lowering effect.
Summary: This study provides very strong evidence that in patients at risk for vascular events, ACE-inhibitor therapy with ramipril significantly reduces cardiovascular death, MI, stroke, heart failure, and revascularization, even in patients with documented normal ejection fractions. Vitamin E therapy does not appear to be beneficial.
DECREASE (Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echo)
Presenter: Don Poldermans, Thoraxcentrum, Erasmus University, Rotterdam, Netherlands.
The study: A multicenter, randomized, open-label study of bisoprolol in high-risk patients undergoing major vascular surgery. A total of 846 patients scheduled for vascular surgery with significant risk factors (age >70 years, angina, diabetes, previous MI, arrhythmias, heart failure, decreased exercise capacity) underwent dobutamine stress echocardiographic studies. Of the 173 patients who were positive, 112 were randomized to bisoprolol (5 mg/d up to 10 mg/d to achieve a heart rate decrease; n=59) or no additional therapy (n=53). The primary end point of the study was the composite incidence of death or nonfatal MI up to 30 days after surgery. The trial was halted prematurely on the recommendation of the Data and Safety Monitoring Board after an interim analysis disclosed a dramatic effect of therapy in reducing events.
The results: At 30 days, the incidence of death or MI was 2 of 59 (3.3%) in the bisoprolol group and 18 of 53 (34.0%) in the control group. Most of the adverse events appeared to take place within ≈7 days of surgery.
Summary: In selected high-risk patients undergoing major vascular surgery, bisoprolol significantly reduces perioperative adverse events.
ASAP (Antioxidant Supplementation in Atherosclerosis Prevention)
Presenter: Jukka T. Salonen, Kuopio, Finland.
The study: A single-center, stratum-randomized, placebo-controlled trial testing the effect of combined vitamin E/vitamin C supplementation on the progression of carotid atherosclerosis in patients at risk for atherosclerotic disease. (Theoretically, combining vitamin C with vitamin E can overcome some of the deleterious pro-oxidant effects of vitamin E.) A total of ≈500 subjects 45 to 69 years old with total cholesterol ≥192 mg/dL (including 50% smokers and 50% men) were randomized to receive either 250 mg BID slow-release vitamin C/d, 100 IU BID vitamin E per day, both therapies together, or placebo. Double-blind treatment continued for 3 years. Carotid ultrasound studies were performed every 6 months. The primary end point of the study was the mean annual increase in the common carotid intimal/medial thickness (CC-IMT), as measured by ultrasound. Separate analyses were conducted in the 4 randomized strata of smoking/nonsmoking men and women.
The results: There was no significant effect of vitamin C, E, or combination therapy in women. In smoking women, the relative risk of CC-IMT progression was 1.0, 0.76, 0.69, and 1.48 for placebo, vitamin E, vitamin C, and combination therapy, respectively. In nonsmoking women, the relative risk of progression was 1.0, 1.13, 0.49, and 1.18, respectively. There was a prominent, highly significant effect of combination therapy in reducing the rate of CC-IMT progression in smoking men, in whom the relative risk of CC-IMT progression was 1.0, 0.21, 0.45, and 0.07 for placebo, vitamin E, vitamin C, and combination therapy, respectively. In nonsmoking men, the relative risk of progression was 1.0, 1.07, 0.3, and 0.55, respectively. The authors speculated that differences in the baseline CC-IMT measurements between the 4 strata may help explain the results, given the significantly higher baseline values and progression rates in smoking men.
Summary: Vitamin E/slow-release vitamin C combination therapy may be of benefit in reducing the progression of vascular disease in smoking men. Its role in nonsmoking men and in women remains uncertain and will be examined in ASAP after 6 years of therapy are completed but will also require further study in larger numbers of subjects.
Acute Coronary Syndromes
SYMPHONY (Sibrafiban Versus Aspirin to Yield Maximum Protection from Ischemic Heart Events Post Acute Coronary Syndromes)
Presenter: Eric Topol, Cleveland Clinic, Cleveland, Ohio.
The study: A large-scale, multicenter (670 sites in 33 countries worldwide) trial of sibrafiban (an oral glycoprotein [GP] IIb/IIIa antagonist) versus aspirin in patients after acute coronary syndromes. A total of 9233 patients with recent unstable angina or MI were randomized to aspirin, low-dose sibrafiban (3 to 4.5 mg QD, depending on body weight and creatinine) or high-dose sibrafiban (3 to 6 mg Q 12 hours). Patients were treated for 3 months, and the primary end point of the study was the composite 90-day incidence of death, MI, or severe recurrent angina leading to revascularization.
The results: There was no significant difference between groups in the primary composite end point (aspirin 9.8%, low-dose sibrafiban 10.1%, high-dose sibrafiban 10.0%); in the individual components of death (1.8%, 2.0%, and 2.0%, respectively), MI (5.6%, 5.8%, and 6.5%, respectively), or severe recurrent ischemia leading to intervention (3.2%, 2.8%, and 2.5%, respectively); or in the composite of death/MI (5.6%, 5.8%, and 6.5%, respectively). In patients undergoing coronary intervention (n=1453), patients on aspirin alone tended to have somewhat better outcomes. No dose-response effect was noted. The incidence of major bleeding was significantly higher in the sibrafiban groups.
Summary: In patients with recent acute coronary syndromes, sibrafiban alone was not superior to aspirin alone (and somewhat inferior in some circumstances) and was associated with significantly higher rates of bleeding. The future of this class of agents is uncertain and will await the results of ongoing large-scale trials with other compounds.
Presenter: Robert Giugliano, Brigham and Women’s Hospital, Boston, Mass.
The study: A randomized, placebo-controlled, dose-ranging trial of klerval (a platelet GP IIb/IIIa antagonist that comes in both an intravenous and an oral form) in patients with recent (within 72 hours) acute coronary syndromes (unstable angina, non–ST-elevation MI [without lytic], or ST-elevation MI [with lytic]). Qualifying patients (n=192) were randomized to receive either intravenous placebo or klerval for 24 to 96 hours. Klerval patients subsequently went on to oral therapy (6 different doses: 175 mg BID, 200 mg BID, 150 mg TID, 250 mg BID, 300 mg BID, or 200 mg TID) for 4 weeks; placebo patients continued on BID or TID placebo. The primary end points related to tolerability and safety; selected sites performed platelet aggregation studies.
The results: There was relatively little in the way of dose-related effects of oral klerval therapy on receptor occupancy across the range of oral doses studied (350 to 600 mg/d). For a given degree of receptor occupancy, platelet inhibition tended to be higher with intravenous versus oral klerval therapy. The incidence of major hemorrhage was 10% in all the klerval groups combined versus 3% with placebo (P=NS). The incidence of thrombocytopenia (<90 000 mm3) was 13% with klerval versus 4% with placebo.
Summary: Combined intravenous/oral GP IIb/IIIa antagonist therapy with klerval was feasible but was associated with a somewhat high incidence of thrombocytopenia, a slight but nonsignificant increase in major bleeding events, and relatively little in the way of a dose-response effect. Future clinical development of this compound has been discontinued.
PRISM (Platelet Receptor Inhibition in Ischemic Syndrome Management) Troponin Substudy
Presenter: Christian Hamm, Krackhoff Heart Center, Bad Neuheim, Germany.
The study: A substudy of the PRISM study (which compared the GP IIb/IIIa antagonist tirofiban with heparin in patients with unstable angina) examining whether troponin measurements may help identify patients who benefit from IIb/IIIa antagonist therapy. From the overall study cohort of 3232 patients, admission troponin T (TnT, ELISA, diagnostic cutoff 0.1 μg/L) and troponin I (TnI, ELISA, diagnostic cutoff 1.0 μg/L) measurements were obtained in 2240 patients. TnT was elevated in 29% of patients, and TnI was elevated in 28% of patients. Both TnT and TnI were useful surrogate markers; troponin-positive patients on heparin alone had significantly more events (≈2.5 times more) than troponin-negative patients or troponin-positive patients treated with tirofiban. The incidence of revascularization was 34% in TnI-positive patients getting heparin, 19% in TnI-positive patients getting tirofiban, 17% in TnI-negative patients getting heparin, and 21% in TnI-negative patients getting tirofiban. Conversely, when patients were stratified into those treated with and without revascularization, the incidence of death/MI in patients with high TnI receiving heparin was more than twice that noted in patients who were TnI-negative or TnI-positive treated with tirofiban. These differences were significant both for patients with and without revascularization. Interestingly, hospital lengths of stay were approximately twice as long in TnI-positive patients getting heparin than in TnI-positive patients getting tirofiban and TnI-negative patients (getting either heparin or tirofiban). In troponin-positive patients, treating 11 patients with tirofiban will prevent 1 death or MI.
Summary: TnT and TnI appear to be reliable indicators of increased risk and can identify patients who may benefit from GP IIb/IIIa antagonist therapy. This benefit is demonstrable in both interventionally and noninterventionally managed patients.
MOXCON (Moxonidine for Congestive Heart Failure)
Presenter: Jay Cohn, University of Minnesota, Minneapolis, Minn.
The study: A multicenter (425 sites in 17 countries), randomized, placebo-controlled trial of moxonidine (a centrally acting medazoline receptor antagonist that lowers plasma norepinephrine levels) in patients with class II to IV heart failure. A total of 1933 qualifying patients were randomized to placebo or moxonidine (0.25 mg BID, titrated up to 1.5 mg BID as tolerated). Approximately 50% of the patients were class III; in 60%, the pathogenesis of CHF was ischemic. The primary end point was all-cause mortality; this was an event-driven trial.
The results: The trial was halted prematurely, on the recommendation of the Data and Safety Monitoring Board, because of excess mortality in the moxonidine group (5.4% versus 3.1% with placebo). The differences in mortality arose largely from more frequent sudden death and more deaths due to worsened pump failure. Hospitalizations for CHF (7.3% versus 6.0% with placebo) and new acute MI (1.7% versus 0.6% with placebo) were also more frequent with moxonidine. Moxonidine was associated with more frequent adverse side effects (primarily gastrointestinal). Excess mortality was not associated with a failure to lower norepinephrine levels, which were significantly lowered by moxonidine therapy.
Summary: Despite lowering norepinephrine levels in patients with class II to IV heart failure, moxonidine therapy was associated with an increase in mortality (primarily sudden death and pump failure), more frequent hospitalization, and more new acute MIs as well as more frequent adverse side effects. The mechanism whereby outcomes are worsened remains unknown at present.
WASH (Warfarin/Aspirin Study in Heart Failure)
Presenter: John G.F. Cleland, University of Hull, Kingston on Hull, UK.
The study: A multicenter, randomized, open-label pilot study of antiplatelet and anticoagulant therapy in patients with CHF. A total of 279 patients with a clinical diagnosis of heart failure and documented impaired left ventricular function were randomized to aspirin (300 mg/d), warfarin (target INR 2.5), or no therapy. Approximately 25% to 33% of the patients were class III/IV, 90% were on ACE inhibitors, 40% to 50% were on previous aspirin therapy (which was discontinued in the no-therapy group), and ≈60% had a documented ischemic etiology of CHF.
Although this was primarily designed as a feasibility study, the primary outcome end point was the composite of all-cause mortality, nonfatal MI, and nonfatal stroke.
The results: At a mean follow-up of 27 months, there were no significant differences in the primary end point, although there was a trend toward slightly more events on aspirin therapy (aspirin 32%; warfarin 26%; no therapy 27%). Most of this difference was driven by mortality. The composite of death or cardiovascular hospitalization tended to be lower on warfarin therapy (16% versus 31% with aspirin and 23% with no therapy), whereas rehospitalization for CHF exacerbation was more frequent on aspirin therapy (64% versus 47% with warfarin and 48% with no therapy). Total vascular events were lower in the warfarin group (5% versus 12% with aspirin and 17% with no therapy). Aspirin therapy was associated with more adverse gastrointestinal side effects.
Summary: In this pilot study of patients with CHF, aspirin therapy was not associated with a decrease in mortality and may have had an adverse impact on morbid events. Warfarin therapy was associated with significant improvement in nonfatal events. The forthcoming larger-scale WATCH study will compare aspirin (162.5 mg/d), warfarin (INR 2 to 3), and clopidogrel (75 mg/d).
LIDO (Livosimendon Infusion Versus Dobutamine in Severe Low Output Heart Failure)
Presenter: Ferenc Follath, University Hospital Zurich, Zurich, Switzerland.
The study: A multicenter, randomized, parallel-group study comparing levosimendan (a calcium-sensitizing and afterload-reducing compound) with dobutamine in patients with severe heart failure requiring intravenous inotropic therapy. A total of 203 qualifying patients were randomized to receive intravenous levosimendan (0.1 up to 0.2 μg · kg−1 · min−1) or dobutamine (5 up to 10 μg · kg−1 · min−1) for a period of 24 hours, with detailed hemodynamic monitoring. The primary end point was the presence of significant hemodynamic improvement, defined as an increase in cardiac index of ≥30%, combined with a fall in pulmonary capillary wedge pressure of ≥25%, without the need for additional inotropic or vasodilator therapy.
The results: There was significantly more hemodynamic improvement in the levosimendan group (28%) than in the dobutamine group (15%; P=0.022). Compared with dobutamine, levosimendan therapy resulted in slightly higher cardiac indices but much more dramatic reduction in pulmonary capillary wedge pressures. At 30-day follow-up, the dobutamine group had a higher mortality (17% versus 7.8% with levosimendan) and a higher incidence of death or worsening heart failure (20% versus 9.7% with levosimendan). Similarly, at 6-month follow-up, mortality in the dobutamine group was 38%, compared with 26.2% in the levosimendan group. Overall, levosimendan was better tolerated than dobutamine.
Summary: Compared with dobutamine in patients with severe heart failure requiring intravenous inotropic support, levosimendan results in a higher incidence of acute hemodynamic improvement and significant improvements in clinical outcomes at 30 days and 6 months.
ARTS (Arterial Revascularization Therapy Study)
Presenter: Patrick Serruys, Thoraxcentrum, Rotterdam, Netherlands.
The study: A multicenter (68 sites, 19 countries), randomized, parallel-group study comparing stenting with bypass graft surgery for the treatment of multivessel coronary artery disease. Inclusion criteria included both stable and unstable angina, at least 2 de novo lesions requiring revascularization, and agreement that either option was feasible. A total of 1205 qualifying patients were randomized to stenting or coronary bypass surgery. The average number of lesions treated in both groups was 2.7. The primary end point of the study was the incidence of freedom from major adverse cardiac and cerebrovascular events, including death, MI, stroke, repeat CABG, and repeat PTCA at 1 year.
The results: At 1 year, the incidence of composite primary outcome end points was significantly reduced in the CABG group (12.2% versus 26.5% in the stent group; P<0.001). However, the composite incidence of death/MI/stroke (excluding revascularization) was not significantly different between groups (8.8% with CABG, 9.5% with stent, P=NS). The differences in individual end points were distributed as follows for CABG and stent patients: death, 2.8% versus 2.5%; MI, 4.0% versus 5.3%; stroke, 2.0% versus 1.7%; repeat CABG, 0.5% versus 4.7%; and repeat PTCA, 3.0% versus 12.2%. In-hospital, follow-up, and total costs (in euros) were €6464, €4216, and €10 680 in the stent group and €10 742, €2903, and €13 645 in the CABG group.
Summary: Compared with CABG in patients requiring multivessel revascularization, coronary stenting provides comparable 1-year rates of death/MI/stroke but requires significantly more repeat revascularization procedures. Compared with the previous Emory Angioplasty Surgery Trial (EAST) and Coronary Artery Bypass Revascularization Investigation (CABRI) studies with balloon angioplasty, the revascularization difference between CABG and percutaneous techniques has narrowed with stenting but is not abolished. With stenting at 1 year, there is a net savings of almost €3000 per patient.
BAAS (Balloon Angioplasty and Anticoagulation Study)
Presenter: Jurrien M. ten Berg, St Antonius Hospital, Nieuwegen, Netherlands.
The study: A randomized, single-center trial comparing aspirin with aspirin plus warfarin (administered before the procedure) in patients undergoing percutaneous intervention. A total of 1058 patients undergoing elective or urgent percutaneous intervention were randomized to aspirin (300-mg load, 100-mg daily dose, 528 patients, 751 lesions) or aspirin plus warfarin (started before the procedure, target INR 2.1 to 4.8, 530 patients, 778 lesions). The primary efficacy end point of the study was the composite incidence of death, MI, stroke, and target vessel revascularization at 1 year. The primary safety end point was the incidence of major bleeding or access site problems. The overall rate of stent usage in the study was 35%; procedural GP IIb/IIIa antagonists were not allowed; the mean preprocedure INR in the aspirin plus coumarin group was 2.7 (during follow-up, the INR was in range ≈62% of the time).
The results: Overall, at 1 year, the aspirin plus warfarin group had significantly fewer composite events (14% versus 20% with aspirin alone). This benefit was evident early; by 30 days, the aspirin plus warfarin group had significantly fewer composite events (3.4% versus 6.4%, RR 0.53). The individual component events for the warfarin plus aspirin versus the aspirin alone group at 30 days were as follows: death, 0.4% versus 0.6%; MI, 2.6% versus 4.0%; CABG, 0.6% versus 0.6%; repeat PTCA, 2.5% versus 4.4%; and stroke, 0.2% versus 0%. Between 30 days and 1 year, there was a nonsignificant trend in composite events favoring the warfarin group (11.6% versus 15.1%). Bleeding events were more frequent in the warfarin plus aspirin group. Early major bleeding occurred in 1.3% (versus 0.2% with aspirin alone), false aneurysms were noted in 1.9% (versus 0.8% with aspirin alone), and late major bleeding events occurred in 0.9% (versus 0% with aspirin alone). None of the bleeding events were fatal.
Summary: In patients undergoing percutaneous interventional procedures, preprocedure warfarin therapy is associated with a decrease in early and late adverse clinical events. This clinical benefit comes at the cost of an increase in major bleeding and access-site complications.
Percutaneous Ablation of Hypertrophic Cardiomyopathy
Presenter: Hubert Seggewiss, Heart Center NRW, Bad Oeynhausen, Germany.
The study: An observational single-center registry of patients undergoing percutaneous alcohol ablation for hypertrophic obstructive cardiomyopathy. A total of 221 symptomatic patients were treated with percutaneous transluminal septal myocardial ablation to create a controlled MI in a localized area of the septum. The present series includes patients with previous unsuccessful surgical myectomy and dual-chamber pacing. The current technique uses myocardial contrast echocardiographic monitoring to correctly target the involved area and avoid areas of necrosis remote from the septal target area (such as papillary muscle or left ventricular free wall segments).
The results: In this ongoing series, the mean outflow tract gradient was reduced in 92% of patients, from 76 to 20 mm Hg. In 4% of patients, a target septal branch could not be identified. Echocardiographic guidance resulted in a change in the target vessel in 7% of patients. In-hospital mortality was 1.3% (including 1 patient with fatal ventricular fibrillation); ≈7% of patients required permanent pacing for AV block. A large majority of patients were symptomatically improved and demonstrated improved exercise performance. No longer-term treatment-associated complications (other than AV block requiring pacing) were noted out to 1 year of follow-up. Recent longer-term follow-up shows persistent clinical improvement and continued reduction of outflow tract gradients (both at rest and provoked). There were no late major complications, ventricular arrhythmias, or late deaths.
Summary: Percutaneous septal ablation appears to be a safe and effective treatment option in symptomatic patients with hypertrophic obstructive cardiomyopathy.
ARTIST (Angioplasty Versus Rotation for the Treatment of In-Stent Stenosis/Occlusion)
Presenter: Jurgen vom Dahl, Universitäts Klinikum der RWTH Aachen, Aachen, Germany.
The study: A randomized, multicenter (24 European centers) study comparing Rotablator versus balloon angioplasty for the treatment of diffuse in-stent restenosis. A total of 298 patients with in-stent restenosis were randomized to balloon angioplasty or Rotablator. To be included in the study, patients had to have a 10- to 50-mm lesion within a previous stent, be at least 3 months after the initial procedure, have a reference vessel size of 2.5 to 4.0 mm, and have symptomatic angina. Multilesion procedures were excluded. Rotablator therapy was conducted with a stepped-burr approach and a burr/artery ratio of ≥0.7, with adjunctive low-pressure (<6 atm) balloon inflations. All patients received procedural heparin, aspirin, and ticlopidine or clopidogrel. The primary end point of the study was the minimum lumen diameter (MLD) at 6-month follow-up coronary angiography.
The results: Acute procedural success (88% to 89%) and clinical success (85% to 87%) were high. Platelet GP IIb/IIIa antagonists were used in 15% of the Rotablator cases and 4.5% of the balloon angioplasty cases. More uneventful slow-flow dissections and arrhythmias were noted in the Rotablator group. There was a slight excess of in-hospital complications (death, MI, repeat PTCA, CABG, tamponade, bleeding) in the Rotablator group (22 of 152, 14.5%, versus 10 of 146, 6.8%), mainly a result of more frequent vascular and bleeding complications. Composite clinical events (death, MI, target lesion revascularization) were higher in the Rotablator group (20.4% versus 8.9%). At follow-up angiography, the MLD tended to be slightly higher in the PTCA group (1.2 mm, versus 0.99 mm in the Rotablator group), with a significant corresponding decrease in the binary restenosis rate (51.2% versus 64.8%) and the need for repeat intervention (36.2% versus 47.8%). Lesion length and percent diameter stenosis were 2 of the most powerful predictors of recurrent restenosis.
Summary: Patients with in-stent restenosis have a high incidence of recurrent restenosis. In this study using rotational atherectomy followed by low-pressure balloon dilation, conventional balloon angioplasty alone was superior to rotational atherectomy. Lesion length and percent diameter stenosis are the most powerful predictors of developing recurrent restenosis.
Coronary β-Radiation Dose-Finding Study
Presenter: Vitali Verin, University Hospital, Geneva, Switzerland.
The study: A pilot dose-ranging study of β-radiation in the prevention of restenosis after PTCA, conducted in 5 European centers. A total of 181 patients were randomized to receive 9, 12, 15, or 18 Gy of intracoronary radiation with a β-source and a centering balloon. To qualify, patients had to have a de novo lesion ≤15 mm, have a reference diameter of 2.5 to 4.0 mm, and have undergone a successful PTCA procedure. The primary end point of the study was the MLD at the treatment site (including the edges) at follow-up angiography (obtained in 154 of 181 patients, or 85%).
The results: At follow-up angiography, the MLD was 1.68, 1.82, 1.82, and 2.09 mm in the 9-, 12-, 15-, and 18-Gy groups, respectively. The corresponding binary restenosis rates (>50% diameter stenosis) were 27.5%, 15.8%, 17.5%, and 8.3%, respectively. The restenosis rates in nonstented arteries (72% of the patients) were 28.1%, 16.7%, 16.7%, and 4.2%, respectively.
Summary: Intracoronary β-radiation delivery is safe and feasible. A dose of 18 Gy is associated with the highest MLD (2.09 mm) and the lowest binary restenosis rate (8.3%) of the doses tested.
PRAGUE (Primary Angioplasty in Patients Transferred From General Community Hospitals to Specialized PTCA Units With or Without Emergency Thrombolysis)
Presenter: Petr Widimsky, Charles University, Prague, Czech Republic.
The study: A multicenter, collaborative, randomized, parallel-group trial evaluating the feasibility, safety, and efficacy of a strategy of transferring patients with acute MI to centralized interventional facilities. Qualifying patients (acute MI <6 hours, documented ST-segment elevation, presenting to an outside community hospital without a catheterization laboratory; 300 were randomized to receive either aspirin and streptokinase with continued management at the community hospital (strategy A, n=99); aspirin and streptokinase with transfer to a nearby interventional center (strategy B, n=100); or aspirin, heparin, and transfer to a nearby interventional center (strategy C, n=101). All patients received postprocedural froxiparin for 3 days and ticlopidine for 1 month. The primary end point of the study was the composite 30-day incidence of death/MI/stroke.
The results: There were no deaths during or within 30 minutes after transport. Transport times averaged 35 to 38 minutes. Two patients developed ventricular fibrillation during transport, and 2 developed worsening heart failure. The incidence of 30-day composite end points was 23% with strategy A, 15% with strategy B, and 8% with strategy C; death alone was 14% with strategy A, 12% with strategy B, and 7% with strategy C; reinfarction was 10% with strategy A, 7% with strategy B, and 1% with strategy C. Somewhat more bleeding was noted with strategy B.
Summary: Transport of acute MI patients from a community hospital to a central interventional facility is feasible, safe, and associated with significantly improved 30-day outcomes. There were more bleeding complications with the combination of streptokinase and intervention; transfer to an interventional center without lytic therapy was not associated with bleeding complications.
Intro-AMI (Integrilin and Reduced Dose of Thrombolytics for Acute Myocardial Infarction)
Presenter: Uwe Zeymer, Medizinische Klinik II, Klinikum Kassel, Germany.
The study: A phase II, multicenter, randomized, dose-ranging trial of thrombolytic therapy plus a GP IIb/IIIa antagonist in patients with acute MI. A total of 342 qualifying patients were randomized to combination therapy with tissue plasminogen activator (tPA) (25- or 50-mg doses) and eptifibatide (single or double dose, varying strength of the second dose, varying postbolus infusion). A total of 8 doses were used. Depending on the dose group, eptifibatide was given either before or after tPA. The primary end point of the study was the incidence of TIMI grade III flow at 60-minute angiography.
The results: At 60 minutes, the incidence of TIMI grade III flow was 45% to 48% with 25 mg tPA and 44% to 65% with 50 mg tPA. More complete lysis was achieved with a double-bolus regimen (180/90 μg/kg) of eptifibatide when the drug was given after the initiation of thrombolytic therapy. There was no significant increase in major bleeding complications or intracranial hemorrhage.
Summary: The combination of eptifibatide and half-dose tPA provides accelerated fibrinolysis, more so with double-bolus administration of the drug. Eptifibatide appears to be more effective in this regard when given after tPA. A subsequent larger-scale dose-confirmation trial is planned.
PIAF (Pharmacological Intervention in Atrial Fibrillation)
Presenter: Stefan H. Hohnloser, JW Goethe University, Frankfurt, Germany.
The study: A multicenter, randomized, parallel-group trial comparing heart rate control versus attempted maintenance of sinus rhythm in patients with persistent atrial fibrillation. A total of 252 eligible patients (atrial fibrillation >7 days and <365 days) were randomized to either rate control (diltiazem, 180 to 360 mg/d) or rhythm control (amiodarone, defibrillation if necessary with additional subsequent amiodarone). The primary end point of the study was improvement in symptom status (palpitations, dyspnea, dizziness).
The results: In the rhythm control group, amiodarone alone resulted in pharmacological conversion in 23% of patients. Sinus rhythm could be maintained in ≈56% of the amiodarone group. The primary outcome of symptom improvement was not significantly different between groups at 3, 12, 24, or 52 weeks. The rhythm control group performed significantly better on a 6-minute walk test, whereas the rate control group had significantly fewer hospitalizations (largely because cardioversion is generally an inpatient procedure in Germany). Amiodarone was somewhat less well tolerated than diltiazem and had to be discontinued more frequently.
Summary: From the perspective of patient-reported symptoms, rate control and rhythm control provide comparable outcomes. Pharmacological cardioversion with amiodarone is successful in ≈25% of patients, and sinus rhythm can be maintained in ≈56%. Exercise performance is significantly better in patients in sinus rhythm. A larger-scale future study, Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM), will explore these issues further.
Reprint requests to James J. Ferguson, MD, Cardiology Research, MC 1-191, Texas Heart Institute, PO Box 20345, Houston, TX 77225.
- Copyright © 1999 by American Heart Association