Highlights of the XXIII Congress of the European Society of Cardiology
The following studies (Table) were presented at the XXIII Congress of the European Society of Cardiology, which was held in Stockholm, Sweden, on September 1 through 5, 2001.
Presenter: Marie-Claude Maurice, MD, Hospitalier Jacque Cartier, Massy, France
The study: A randomized, double-blind, parallel-group trial comparing a stent coated with sirolimus (an immunosuppressive macrolide antibiotic; n=120) with a similar uncoated stent (BX Velocity; n=118) in patients undergoing stent implantation. Qualifying patients had to have de novo single-vessel disease in a native coronary artery that was <18 mm in length and 2.5 to 3.5 mm in diameter. The primary end point was in-stent lumen diameter loss measured at 6-month follow-up angiography.
The results: Mean reference vessel size was 2.6 mm; mean lesion length was 9.6 mm. Late loss in the control uncoated stent was 0.80±0.53 mm; late loss with the sirolimus-coated stent was 0.01±0.33 mm (P<0.001). The binary restenosis rate was 2.6% with the uncoated stents and 0% with the coated stents. Preliminary long-term clinical follow-up (to 210 days) showed a target lesion revascularization rate of 26% in the uncoated stent group versus 0% in the coated stent group (P<0.0001). Survival free from major adverse cardiovascular events was 73% in the uncoated stent group and 97% in the coated stent group (P<0.001) when used for the treatment of discrete lesions.
Summary: Sirolimus-coated stents seem to have virtually no restenosis (at 6 months) in native vessels that are 2.5 to 3 mm in diameter. These exciting data will need to be confirmed in larger trials, in other lesion types, and with longer-term follow-up.
Presenter: Christian W. Hamm, MD, Kerckhoff Heart Center, Bad Nauheim, Germany
The study: A multicenter, randomized trial evaluating a silicon carbide stent for revascularization of patients with acute coronary syndromes. A total of 485 patients (314 in Braunwald class IIb and 171 in class IIIb) were randomized to receive either a conventional stent (n=247) or a silicon carbide stent. The primary end point was the composite of death, myocardial infarction, or ischemia-driven target lesion revascularization at 6 months.
The results: Percutaneous coronary intervention was performed 0.4±1.1 days after admission; 76% of interventions were performed on the first day. Procedural success, clinical success, primary composite outcome events, and restenosis were all similar between groups. Overall, 6-month clinical event rates were low (≈10%). At longer-term follow-up (to 274 days), there was still no difference between groups. Although there seemed to be some potential advantages at 6 months in patients with class IIIb unstable angina, by 9 months this was no longer significant.
Summary: A silicon carbide stent provided no significant benefit over a conventional stent in patients with acute coronary syndromes undergoing stent implantation. Overall 6-month event rates were low.
Acute Coronary Syndromes
Presenter: Frans J. Van de Werf, MD, Gasthuisberg University Hospital, Leuven, Belgium
The study: An open-label, randomized, multicenter, parallel-group study comparing full dose tenecteplase (TNK; with weight-adjusted unfractionated heparin [UFH] given intravenously for 48 hours, n=2038), full dose TNK (with the low-molecular-weight heparin enoxaparin given subcutaneously for up to 7 days, n=2040), and half-dose TNK plus abciximab (with weight-adjusted, low-dose, UFH given intravenously for 48 hours) in patients with acute myocardial infarction. The primary end point was the composite of 30-day mortality, in-hospital reinfarction, or in-hospital refractory ischemia. The primary safety and efficacy end point was the above composite plus in-hospital intracranial hemorrhage (ICH) or in-hospital major bleeding.
The results: The primary composite efficacy end point was significantly reduced in both the enoxaparin group (11.4% versus 15.4% with TNK and UFH; P=0.0002) and the half-dose TNK/abciximab group (11.1% versus 15.4% with TNK and UFH; P<0.0001). The primary composite safety and efficacy end point was also significantly reduced in both the enoxaparin group (13.8% versus 17% with TNK and UFH) and the half-dose TNK/abciximab group (14.2% versus 17% with TNK and UFH). Despite the longer administration period for the enoxaparin, even at 48 hours there was significant efficacy benefit (6.1% with TNK plus enoxaparin and 5.2% with half-dose TNK plus abciximab versus 8.8% with TNK plus UFH) and safety and efficacy benefit (8.1%, 8.2%, and 10.3%, respectively). In terms of the individual efficacy end points, there was no significant difference in 30-day mortality (5.35%, 6.59%, and 5.99%, respectively), but significant reductions in both in-hospital reinfarction (2.6%, 2.2%, and 4.2%, respectively) and in-hospital refractory ischemia (4.6%, 3.2%, and 6.5%, respectively). In terms of the safety end points, there were no significant differences in ICH (0.88%, 0.94%, and 0.93%, respectively) and slight but significant increases in major bleeding events (3.0%, 4.3%, and 2.2%, respectively).
Summary: In patients with acute myocardial infarction, both TNK plus enoxaparin and half-dose TNK plus abciximab (with low-dose weight-adjusted UFH) are significantly superior to TNK and standard UFH. There are slight increases in major bleeding, but the overall rate of major bleeding was low.
Presenter: Elliott Antman, MD, Brigham and Women’s Hospital, Boston, Mass
The study: A randomized, multicenter, dose-ranging trial of enoxaparin as adjunctive antithrombin therapy for pharmacological reperfusion in patients with acute myocardial infarction (MI). Patients with ST-segment elevation MI at 43 international centers were randomized to either standard-dose tenecteplase (TNK) with unfractionated heparin (UFH), standard-dose TNK with enoxaparin (either with or without an initial intravenous bolus), half-dose TNK with abciximab and reduced-dose UFH, or half-dose TNK with reduced-dose enoxaparin (low dose, either with or without intravenous bolus, or medium-dose without a bolus). The primary efficacy end point was TIMI flow grade at 60-minute angiography. The primary safety end point was TIMI major hemorrhage.
The results: Preliminary findings in 456 patients were presented. There were no significant differences between groups in TIMI flow grade at 60 minutes. Major bleeding complications were slightly lower with enoxaparin in patients receiving half-dose TNK (5.6% versus 7.8% with UFH) and similar with the 2 antithrombins in patients receiving full-dose TNK (1.9% with enoxaparin and 1.4% with UFH). Looking at indirect markers of reperfusion, complete ST-segment resolution at 60 minutes was not substantially different between groups (20% for TNK/UFH, 19% for TNK/enoxaparin, 27% for TNK/abciximab/UFH, and 19% for TNK/abciximab/enoxaparin); however, at 180 minutes, more prominent differences emerged (37% for TNK/UFH, 47% for TNK/enoxaparin, 51% for TNK/abciximab/UFH, and 59% for TNK/abciximab/enoxaparin). The clinical composite outcome of death/MI also seemed improved with combination therapy (14.9% for TNK/UFH, 4.4% for TNK/enoxaparin, 6.2% for TNK/abciximab/UFH, and 4.8% for TNK/abciximab/enoxaparin).
Summary: In patients with ST-segment elevation MI at 60 minutes after the onset of therapy, enoxaparin is as effective as UFH with respect to angiographic observations. However, ST-segment resolution at 180 minutes and clinical outcomes (death and MI) seem to be improved with both the addition of abciximab and the use of enoxaparin instead of UFH. These effects seem to be additive. The use of abciximab in a pharmacological reperfusion regimen does seem to increase the risk of major bleeding.
Presenter: Harvey D. White, MD, DSc, Green Lane Hospital, Auckland, New Zealand
The study: An open-label, multicenter, worldwide, randomized, parallel-group study in 17 073 patients with acute myocardial infarction treated with streptokinase comparing adjunctive therapy with unfractionated heparin (UFH; adjusted to an activated partial thromboplastin time [aPTT] of 50 to 75 s) and the direct thrombin antagonist bivalirudin (not adjusted for aPTT; n=8516). The primary end point of the study was 30-day mortality.
The results: The study included a relatively high-risk population, including a high number of women and patients from Eastern Europe and Russia. Mean time to therapy was 3.1 hours. aPTTs were significantly higher in the bivalirudin group. There was no significant difference between groups in risk-adjusted 30-day mortality (bivalirudin, 10.5%; UFH, 10.9%). However, there was a significant reduction in adjudicated reinfarction at 96 hours (bivalirudin, 1.5%; UFH, 2.2%; P=0.002) and a nonsignificant trend toward more severe bleeding, although severe bleeding event rates were low (0.7% versus 0.5%). Moderate (1.4% versus 1.0%) and mild (12.6% versus 8.9%) bleeding rates were significantly increased, although transfusions were not significantly higher in the bivalirudin group (1.4% versus 1.1%, P=0.11). Concomitant stroke rates were slightly but not significantly increased (1.25% versus 0.96%).
Summary: In patients with acute myocardial infarction treated with streptokinase, bivalirudin (in comparison with UFH) did not significantly reduce mortality, but it did reduce the incidence of recurrent infarction.
Presenter: A. Michael Lincoff, MD, Cleveland Clinic, Cleveland, Ohio
The study: An open-label, randomized, parallel-group study of 16 588 patients who presented within 6 hours of ST-segment elevation myocardial infarction (MI). Qualifying patients were randomized to receive thrombolytic therapy with either standard-dose reteplase (n=8260) or half-dose reteplase and abciximab (n=8328). The primary end point was 30-day mortality. Secondary end points included other complications of MI.
The results: At 30 days, mortality was 59% in the reteplase group and 5.6% in the reteplase plus abciximab group (P=NS). The incidence of reinfarction (2.3% versus 3.5% with placebo; P<0.0001) and the need for urgent revascularization within the first 6 hours (5.6% versus 8.6% with placebo; P<0.0001) were significantly lower in the reteplase plus abciximab group. Bleeding events were significantly increased with combination therapy, and although the overall incidence of ICH was not increased in patients ≥75 years, there was a trend toward a substantially higher ICH rate. The data were presented on a subset of patients (n=1173) going on to coronary intervention and a small subset of patients (n=207) who had ST-segment monitoring. In the intervention subset, there was no evidence of augmented mortality benefit at 30 days with combination therapy (6.7% versus 5.4% with placebo; P=NS), although the incidence of recurrent MI at 7 days was lower (2.8% versus 4.8% with placebo), which was similar to results in the overall patient cohort. The time to steady-state ST-segment and the percentage of patients with nonstabilized ST-segments were both significantly lower with combination therapy.
Summary: In patients with acute MI, combination therapy with reteplase and abciximab results is more rapid and more complete ST-segment resolution, less reinfarction, and less early emergent revascularization but no significant mortality benefit at 30 days.
Presenter: Harold Arnesen, MD, Ulleval University Hospital, Oslo, Norway
The study: A randomized, multicenter, parallel-group study comparing aspirin (160 mg/d; n=1206), warfarin (adjusted to an international normalized ratio [INR] of 2.8 to 4.2; n=1216) and aspirin (75 mg) plus warfarin (adjusted to an INR of 20 to 25; n=1205) in patients after myocardial infarction in 20 clinical centers in Norway. Patients were followed for 4 years. The primary end point was death, reinfarction, or thromboembolic cardiovascular accident.
The results: The mean INR in the warfarin group was 2.8; the mean INR in the warfarin plus aspirin group was 2.2. The mean follow-up was 1445 days. The incidence of composite primary outcome events at 4 years was 24.5% with aspirin, 19.4% with warfarin, and 17.4% with warfarin plus aspirin (P=0.00001 versus aspirin, P=0.2 versus warfarin). The incidence of bleeding was 0.15% per year with aspirin, 0.58% per year with warfarin, and 0.52% per year with warfarin plus aspirin. There were no significant differences in the need for interventional procedures between groups.
Summary: In patients after myocardial infarction, warfarin and warfarin plus aspirin are significantly better than aspirin alone in reducing long-term clinical events. There is a slightly increased risk of major bleeding but, overall, major bleeding events were infrequent.
Presenter: Shamir Mehta, MD, McMaster University Medical Center, Hamilton, Ontario, Canada
The study: As previously reported, the CURE trial4 randomized 12 562 patients with unstable angina/non-ST-segment elevation myocardial infarction (MI) to either aspirin alone (75 to 325 mg/d) or aspirin plus clopidogrel (300 mg oral load, then 75 mg/d). Treatment was continued for 3 to 12 months (mean, 9 months). Patients receiving glycoprotein IIb/IIIa antagonists within the past 3 days were excluded. PCI-CURE involved 2658 patients in the CURE trial who underwent PCI during the course of the study. After PCI, most patients (>80%) received open-label thienopyridine for ≈4 weeks, after which study drug was restarted and continued for a mean of 8 months. The primary end point was a composite of cardiovascular death, MI, or urgent target vessel revascularization within 30 days of PCI.
The results: Patients were pretreated for a median of 6 days before PCI during the initial hospitalization (n=1730) and for a median of 10 days overall. The primary end point was significantly reduced in the combination therapy group (4.5% versus 6.4% with aspirin alone; relative risk, 0.70; 95% confidence interval, 0.50 to 0.97; P=0.03). There was also a significant reduction of events, both before PCI (MI, 3.6% versus 5.1%, P=0.04; MI or refractory ischemia, 12.1% versus 15.3%, P=0.008) and from PCI to the end of follow-up (cardiovascular [CV] death or MI, 6.0% versus 8.0%, P=0.047; CV death, MI, or any revascularization, 18.3% versus 21.7%, P=0.03). Total events (before and after PCI) were also significantly reduced with combination therapy (CV death or MI, 8.8% versus 12.6%, P=0.002). Between 30 days after PCI and long-term followup, there was a significant reduction in CV death, MI, and rehospitalization with clopidogrel compared with placebo (25.3% versus 28.9%, relative risk, 0.86; P=0.046). Major bleeding and life-threatening bleeding were similar between groups, both from PCI to 30 days and from PCI to the end of follow-up, although minor bleeding through follow-up was more frequent with combination therapy.
Summary: In the subset of CURE patients undergoing PCI, a period of pretreatment with clopidogrel plus aspirin followed by long-term therapy for up to one year resulted in better clinical outcomes than aspirin alone, with no significant increase in major or life-threatening bleeding complications.
Presenter: Paul Touboul, MD, Hopital Cardiologique Louis Pradel, Lyon, France
The study: A randomized comparison of angioplasty and prehospital thrombolysis in patients with acute myocardial infarction (MI). The primary end point was the composite of all-cause mortality, recurrent MI, and disabling stroke. The sample size was originally estimated at 1200 patients to detect a reduction in events from 12.2% to 7.2% with 85% power. The study was conducted in 7 cities in France between June 1997 and September 2000. The enrollment showed a definite slowing in the last year, accounting for a less than expected inclusion rate. At the end of the trial, there were 419 patients in the prehospital thrombolysis group and 421 patients in the primary percutaneous coronary intervention (PCI) group.
The results: The incidence of primary composite outcome events was 8.2% in the prehospital thrombolysis group and 6.2% in the primary PCI group (P=0.29, NS). Individual end points of death (3.8% with thrombolysis versus 4.8% with PCI), reinfarction (3.7% versus 1.7%, respectively) and disabling stroke (1.0% versus 0%, respectively) were also not significant between groups. Urgent angioplasty was performed in 33% of the prehospital thrombolysis group.
Summary: In patients with acute MI, this study failed to demonstrate any significant difference in clinical outcomes between prehospital thrombolysis and primary PCI.
Presenter: Uwe Zeymer, MD, Staedtische Kliniken, Kassel, Germany
The study: A 2-part series of double-blind studies investigating the use of the Na/H exchange inhibitor eniparide in patients with acute myocardial infarction who were treated with either thrombolytic therapy or primary percutaneous coronary intervention (PCI). In stage I of the study, 4 doses of eniparide (50, 100, 150, and 200 mg) were compared with placebo in 430 patients, with 2 doses (100 and 150 mg) subsequently chosen for subsequent larger scale testing versus placebo in 969 patients in stage II. The primary end point for both stage I and stage II was enzymatic infarct size.
The results: In stage I, enzymatic infarct sizes in the placebo and 50, 100, 150, and 200 mg of eniparide groups were 44, 45.3, 40.2, 33.9, and 43.9 mm, respectively. On the basis of these findings, stage II compared placebo with 100 and 150 mg of eniparide. In stage II, however, there were no significant differences among groups in infarct size (41.2, 43, and 41.5 mm, respectively). There was no treatment effect noted in either anterior infarcts or in patients undergoing primary PCI. Similarly, there were no differences in clinical events between groups.
Summary: In acute myocardial infarction, patients undergoing reperfusion with either thrombolytic therapy or primary PCI, the Na/H exchange inhibitor eniparide was no better than placebo. There were no differences in infarct size or clinical outcomes between groups.
Congestive Heart Failure
Presenter: James A. Coman, Jr, MD, Oklahoma Heart Institute, Tulsa, Okla
The study: A randomized trial evaluating cardiac resynchronization therapy (CRT; biventricular pacing using the Contak-CD device) in patients with congestive heart failure (CHF) who already have an implantable defibrillator. A total of 581 patients with class II to IV CHF or an ejection fraction <35%, a QRS complex ≥120 ms, normal sinus node function, and indications for defibrillator therapy were enrolled; 490 were ultimately randomized. The study included patients from a crossover design trial, a parallel group trial, and from the phase II investigational experience. Analysis were stratified on the basis of all patients and more symptomatic (class III/IV) patients.
The results: Approximately one-third of patients were class II, 69% had an ischemic cause of CHF. The mean ejection fraction was 21%. There were no significant differences on clinical outcome events or in 6-minute walk performed between groups. Overall event rates were somewhat lower than prestudy predictions. Over time, there was improvement in peak V̇o2 in the resynchronization patients. There was an indication of functional improvement (higher 6-minute walk scores) in more symptomatic patients.
Summary: In patients with class II to IV CHF, there was no clinical benefit of CRT when added to baseline defibrillator therapy; there was some benefit in peak V̇o2. There was a suggestion that CRT may provide some functional benefit in more symptomatic patients, but this needs to be confirmed in additional studies.
Presenter: John R. Teerlink, MD, San Francisco Veterans Administration Medical Center/University of California at San Francisco, San Francisco, Calif
The study: A multicenter, double-blind, placebo-controlled trial of tezosentan (a parenteral dual endothelin receptor A/B antagonist) in patients with congestive heart failure. A total of 669 symptomatic, hospitalized, acute heart failure patients were randomized to an infusion of tezosentan (25 mg/h for1 hour, then 50 mg/h for 23 to 72 hours; n=331) or placebo (n=338). The primary end point was the patient-reported dyspnea assessment.
The results: There were no significant differences between groups in patient-reported dyspnea, dyspnea score, and clinical end points of time to worsening heart failure or death. There was a higher incidence of hypotension with tezosentan; there was no difference in mortality between groups.
Summary: This study, in contrast to prior studies of tezosentan, showed no improvement in the symptoms of dyspnea in hospitalized patients with acute heart failure.
Neuropsychological Outcomes in SOS
Presenter: Peter Wahrborg, MD, Gotheborg, Sweden
The study: The original SOS study compared stenting to bypass surgery in 988 patients with multivessel coronary artery disease. The present study is a subset of 153 patients in whom detailed neuropsychological testing was performed to assess the impact of revascularization strategy or cognitive function. Testing was done at baseline, at 6 months, and at 12 months to assess changes over time.
The results: In contrast to prior studies, there was no difference in neurocognitive function at baseline, 6 months, or 12 months. Depression scores were also similar between groups.
Summary: In contrast to prior studies suggesting that bypass surgery may be associated with significant neurocognitive impairment, this study showed no difference between stenting and surgery. These results need to be corroborated in additional studies.
Presenter: John Chambers, Institute for International Health, Sydney, Australia
The study: A randomized, placebo-controlled trial of blood pressure-lowering therapy in patients with a history of prior stroke. After a 4-week placebo run-in phase, a total of 6105 patients with prior stroke were randomized to perindopril (an ACE inhibitor, 4 mg) plus indapamide (a diuretic, 2.5 mg) or to placebo and followed for 4 to 5 years. The primary end point was the incidence of total recurrent stroke.
The results: There was a 28% relative decrease in the incidence of stroke in the perindopril/indapamide group (8.5% versus 14.4% with placebo). In patients who developed a recurrent stroke, treatment was also associated with a lower incidence of dementia and less cognitive decline. Major vascular events and major coronary events were also significantly decreased. The favorable effects on clinical outcome were present in both hypertensive and nonhypertensive patients. For patients treated for 5 years, there was a reduction of 1 stroke for every 23 treated patients and 1 vascular event for every 11 treated patients.
Summary: In patients with a history of stroke, the combination of perindopril and indapamide provides a significant reduction in recurrent stroke, major coronary events, and major vascular events. These benefits are present in both hypertensive and nonhypertensive patients.
Presenter: Marc A. Pfeffer, MD, PhD, Brigham & Women’s Hospital, Harvard Medical School, Boston, Mass
The study: A randomized, controlled trial of the effects of irbesartan (an angiotensin-II receptor antagonist) on the progression to renal dysfunction in patients with type II diabetes. To qualify for the study, patients had to have type II diabetes, proteinuria (>900 mg/d), elevated creatinine, and hypertension. A total of 1715 qualifying patients from 210 clinical centers were randomized to irbesartan (150 to 300 mg/d, n=572), amlodipine (5 to 10 mg/d, n=565), or an antihypertensive therapy that was not an angiotensin-II receptor blocker or a calcium-channel blocker (control group, n=569). Patients were followed for a mean of 6 years. The primary end point was significant progression of renal disease (doubling of the creatinine or progression to end-stage renal disease/dialysis).
The results: The degree of blood pressure lowering was comparable in all 3 groups. Irbesartan use was associated with a 20% relative reduction in progression to renal failure. The time to an end point clinical event was also prolonged by ≈6 months with irbesartan. There was no significant effect on mortality or overall cardiovascular events, but total hospital admissions were also reduced with irbesartan.
Summary: In these high-risk, type II diabetic patients with proteinuria, hypertension, and elevated creatinine, irbesartan seemed to be somewhat protective for the progression of renal disease but not for mortality or cardiovascular events. This effect was independent of the degree of blood pressure control.
Presenter: Matthias E. Pfisterer, MD, University Hospital, Basel, Switzerland
The study: A multicenter, randomized comparison of revascularization versus medical therapy in elderly (≥75 years) patients with chronic coronary artery disease (CAD). The study was conducted in 14 clinical centers in Switzerland. Elderly patients with symptomatic, chronic CAD (excluding acute myocardial infarction within 10 days) were randomized to an invasive strategy (catheterization plus revascularization as needed; n=153) or medical management (n=148). The primary end point was an assessment of quality of life; clinical events were also recorded. Patients were followed for 6 months.
The results: The mean age was 80 years, and 18% to 19% of subjects had prior revascularization. Revascularization was performed in approximately one-third of the patients randomized to medical therapy; ≈75% of the intensively managed patients were subsequently revascularized. Invasively managed patients had a substantially higher quality of life, greater improvement in symptoms, and required fewer medications. Although mortality tended to be somewhat higher in the invasive group (8.5% versus 4.1% in the medical group), overall event-free survival (freedom from death/myocardial infarction/recurrent hospitalization) was substantially higher in the invasive group (81% versus 51% in the medical group).
Summary: In elderly patients (≥75 years) with chronic CAD, an invasive strategy and medical management both convey benefit, but the quality of life and clinical outcomes seem better with invasive management (with a somewhat higher concomitant mortality risk). Approximately one-third of the medically treated patients needed revascularization; ≈75% of the invasively managed patients were suitable candidates for revascularization.
Presenter: Alberta Zanchelti, MD, University of Milan, Milan, Italy
The study: A randomized, placebo-controlled trial of lacidipine (a third-generation, slow-onset, long-acting, highly lipophilic calcium antagonist) on the progression of carotid atherosclerosis in patients with hypertension. A total of 2334 patients in 7 European countries were recruited from 410 clinical centers and referred to 23 central referral centers for carotid ultrasound studies. After a 1-month placebo run-in phase, patients were randomized to either lacidipine (4 mg) or atenolol (50 mg). The doses were increased and a diuretic was added (if necessary) to achieve blood pressure control. Patients were treated for up to 4 years. The primary end point of the study was an ultrasound assessment of intimal-medial thickness. Clinical events were also documented.
The results: Of the 1157 patients randomized to atenolol and the 1177 patients randomized to lacidipine, 764 and 755, respectively, completed ultrasound follow-up. The mean change overline in ultrasound-assessed intimal-medial thickness was significantly lower with lacidipine (0.039 mm versus 0.048 mm with atenolol). The rate of progression was also significantly lower with lacidipine, despite comparable decreases in systolic and diastolic blood pressure. The atenolol group was noted to have a decrease in HDL cholesterol and an increase in triglycerides. The overall incidence of cardiovascular events was low and not significantly different between groups.
Summary: In patients with hypertension, treatment with lacidipine over a 4 year period results in significantly less progression of carotid atherosclerosis than treatment with atenolol.
Atrial Fibrillation Therapy Study
Presenter: A. John Camm, MD, St. George’s Hospital, London, UK
The study: A prospective, randomized trial investigating the utility of conventional pacing and atrial fibrillation (AF) prevention pacing in reducing the incidence of recurrent AF episodes. A total of 372 patients with drug-refractory AF received an upgradable dual-chamber pacemaker. In the first conventional pacing phase (2 months), patients were randomized to 1 of 5 pacing modes: DDD at 40 beats/min, DDD at 70 beats/min, DDD at 85 beats/min, DDDR at 75 beats/min, and DDDR at 85 beats/min. In the second AF prevention pacing phase (2 months), patients were randomized to DDD 70 beats/min, with or without AF prevention pacing. The primary outcome was AF burden (hours/day in AF).
The results: In the conventional pacing phase, there was no significant effect of conventional pacing on AF burden, AF recurrence, or average duration of sinus rhythm. In contrast, AF prevention pacing significantly reduced AF burden and AF recurrence and prolonged the average duration of sinus rhythm.
Summary: In contrast to conventional pacing (which has no effect), AF prevention pacing significantly reduces AF burden and AF recurrence and prolongs the average duration of sinus rhythm.
Presenter: T. Fetsch, MD, Munich, Germany
The study: A randomized, prospective, placebo-controlled trial in patients with chronic atrial fibrillation undergoing DC cardioversion. A total of 848 qualifying patients were randomized after cardioversion to receive placebo (n=88), sotalol (n=383), or quinidine/verapamil (n=377). The primary end point was the time to first recurrence or death. In the out-of-hospital period, patients were followed with daily transtelephonic ECGs.
The results: Overall, 70% of ECG-documented recurrences were asymptomatic. Active therapy was associated with a 2 to 3-fold decrease in the recurrence rate. Quinidine/verapamil and sotalol were equally efficacious in reducing the incidence of any recurrence; quinidine/verapamil was more effective in reducing the recurrence of chronic atrial fibrillation. The risk of the 2 drugs was comparable, with the exception of torsades de pointes, which was rarely noted with sotalol.
Summary: In light of the fact that most ECG-documented recurrences were asymptomatic, the definition of “recurrent” atrial fibrillation for clinical trials may need to be re-evaluated. In patients with chronic atrial fibrillation, sotalol and quinidine/verapamil are both effective in reducing recurrent episodes of atrial fibrillation after DC cardioversion; quinidine/verapamil may be somewhat superior in reducing chronic recurrences.
Presenter: Roumen Nakuv, MD, International Institute of Thrombosis and Vascular Diseases, Frankfurt, Germany
The study: A randomized, placebo-controlled trial of darusentan (an oral endothelin A receptor antagonist) for the treatment of hypertension. After a 2-week placebo run-in phase, a total of 392 patients with hypertension (diastolic blood pressure, 100 to 109 mm Hg) were randomized to placebo or 1 of 3 doses of darusentan (10, 30, or 100 mg/d). Therapy continued for up to 7 weeks. The primary end point was the effect on blood pressure at follow-up.
The results: There was a significant, dose-dependent decrease in both systolic and diastolic blood pressure with darusentan. Importantly, this fall in blood pressure was not accompanied by an increase in heart rate. There was a higher incidence of patient-reported adverse events (headache and flushing) in the 100-mg group.
Summary: In patients with hypertension, the darusentan produced a dose-dependent decrease in blood pressure that was not associated with an increase in heart rate. The 100-mg group had a higher incidence of patient-reported side effects.