doi: 10.1161/01.CIR.0000029759.28581.E2
(Circulation. 2002;106:e24.)
© 2002 American Heart Association, Inc.
Meeting Highlights
Highlights of the 51st Annual Scientific Sessions of the American College of Cardiology
From the St Luke’s Episcopal Hospital, Texas Heart Institute, Baylor College of Medicine, the University of Texas Health Science Center at Houston.
Correspondence to James J. Ferguson, MD, Cardiology Research, MC 1-191, Texas Heart Institute, PO Box 20345, Houston, TX 77225-0345. E-mail jferguson{at}heart.thi.tmc.edu
The following studies were presented at the 51st Annual Scientific Sessions of the American College of Cardiology in Atlanta, Ga, March 17–20, 2002.
Hypertension
LIFE (Losartan Intervention For Endpoint Reduction in Hypertension Study)
The Presenter:
Björn Dahlöf, MD, Göteborg University, Sweden
The Study:
A randomized, double-blind, parallel group study of losartan (a selective angiotensin I receptor blocker)–based versus atenolol-based therapy in 9193 patients with essential hypertension and ECG evidence of left ventricular hypertrophy (LVH).1 To base therapy (both up to a maximum of 100 mg), diuretics and other antihypertensive agents (excluding angiotensin-converting enzyme inhibitors, other angiotensin receptor blockers, or ß-blockers) could be added. Study therapy was continued for 
4 years; the primary end point was the composite of cardiovascular mortality, stroke, and myocardial infarction.
The Results:
The degree of blood pressure control was similar between groups. There were significantly fewer cardiovascular events in the losartan group (11% versus 13%, P=0.021), and the primary difference was a reduction in the number of strokes (5% versus 7%, P=0.001). Regression of LVH on the ECG was also significantly more frequent with losartan. Intriguingly, with losartan, there was a 25% reduction in the number of patients who developed diabetes, and in the subgroup of patients with diabetes, total mortality was reduced by 39%.
Summary:
In hypertensive patients with ECG evidence of LVH, outcomes with losartan are significantly better than with atenolol. This benefit is particularly manifested in patients with diabetes. It is also worth noting that the likelihood of developing diabetes was also reduced with losartan.
4E (Epleronone, Enalapril, and Eplerenone/Enalapril Combination Therapy in Patients With Left Ventricular Hypertrophy)
The Presenter:
Bertram Pitt, MD, University of Michigan, Ann Arbor
The Study:
A double-blind, randomized parallel group trial comparing eplerenone (a selective aldosterone blocker, 200 mg/d), enalapril (an angiotensin-converting enzyme inhibitor, 40 mg/d), and eplerenone (200 mg/d) plus enalapril (10 mg/d) in 202 patients with essential hypertension and left ventricular hypertrophy on ECG. Additional add-on antihypertensive therapy with hydrochlorothiazide and/or amlodipine was permitted. Study drug therapy was continued for 9 months. The primary end point was left ventricular mass, as measured by MRI. The study was designed as a noninferiority study to show that left ventricular mass would not differ between groups by >15 g.
The Results:
The mean change in left ventricular mass was -14.5 g in the eplerenone group, -19.7 g in the enalapril group, and -27.2 g in the eplerenone/enalapril group. Blood pressure was reduced in all 3 groups, with a trend toward greater reduction with combination therapy. Microalbuminuria and the change in urinary albumin/creatinine ratio were significantly improved with combination therapy.
Summary:
The selective aldosterone antagonist eplerenone alone appears to be as good as enalapril alone, and their combination may be better than either alone in reducing some end-organ sequelae of hypertension.
Acute Coronary Syndromes
DANAMI II (DANish multicenter randomized study on thrombolytic therapy versus acute coronary angioplasty in Acute Myocardial Infarction 2)
The Presenter:
Henning Rud Andersen, MD, PhD, Skejby University Hospital, Aarhus, Denmark
The Study:
A randomized trial comparing 2 management strategies for acute myocardial infarction: on-site treatment with fibrinolytic therapy (100 mg front-loaded tissue plasminogen activator) versus transfer of patients to a tertiary facility for primary PCI. There was no upper age limit for inclusion in the study. The study was conducted in Denmark and involved 5 PCI centers and 24 referring hospitals. The mean transfer distance was 
35 miles, up to a maximum of 95 miles. At the time the study was initiated, only 2 of the 5 centers were actively performing primary PCI procedures (during the daytime) for acute myocardial infarction. The primary end point was a composite of death, reinfarction, or disabling stroke at 30 days. Enrollment in the study was halted prematurely by the Data Safety Monitoring Board because of clear benefit in one of the arms. At the time the study was halted, there were 782 patients in the fibrinolytic arm and 790 in the transfer/PCI arm.
The Results:
Composite events were significantly reduced in the transfer/PCI arm (8.0% versus 13.7% with fibrinolysis). This benefit was present at both referring centers (8.5% versus 14.2%) and invasive centers (6.7% versus 12.3%). Overall, there appeared to be no significant difference in the time from symptom onset to fibrinolysis (160 min) or in the time from symptom onset to balloon inflation (220 min) at referring versus invasive centers. The overall time difference in time to balloon inflation for referral versus invasive centers was only 10 minutes. The incidence of adverse events during transfer was very low, with no deaths and no emergent intubations. Mortality (30-day) was 7.6% in the fibrinolysis group and 6.6% in the transfer/PCI group (P=NS). The overall incidence of disabling stroke was low (2.0% with fibrinolysis, 1.1% with transfer/PCI, P=NS).
Summary:
In Danish patients with acute myocardial infarction, a strategy of transfer to a tertiary PCI facility was superior to on-site initiation of fibrinolytic therapy. The benefits were primarily in a reduction of reinfarction. Caution should be employed before generalizing beyond the logistical constraints with the present study design.
AMISTAD II (Acute Myocardial Infarction STudy of ADenosine II)
The Presenter:
Allan Ross, MD, George Washington University, Washington, DC
The Study:
A randomized, placebo-controlled trial of adenosine in patients with acute myocardial infarction. The rationale for using adenosine was the hope that its potential effect of replenishing high-energy phosphates, reducing platelet aggregation, and facilitating preconditioning (by reducing free radical generation and neutrophil activation) might translate into clinical benefit. A total of 2118 patients with acute myocardial infarction undergoing fibrinolytic therapy (the vast majority of patients) or primary PCI were randomized to receive either low-dose (50 µg · kg-1 · min-1x3 hours) or high dose (70 µg · kg-1 · min-1x3 hours) adenosine. The primary end point was the composite of death, in-hospital congestive heart failure, or readmission for congestive heart failure in the pooled adenosine groups. Infarct size (sestamibi) was also measured in 234 patients. Midway through the study, the Data Safety Monitoring Board met and advised stopping the 50-mg dose group for lack of efficacy. The Food and Drug Administration would not allow the trial to then be upsized or the primary analysis modified.
The Results:
Primary events occurred in 18% of the placebo group and in 16% of the pooled adenosine group (P=NS). There was no benefit of adenosine noted when reperfusion therapy was unsuccessful. There were trends that suggested a differential effect with regard to how soon reperfusion therapy was initiated, with a trend toward the most benefit evident within 2 hours of pain. Infarct size tended to be slightly, but not significantly, lower with adenosine, more so in the high-dose group. Infarct size was strongly correlated with subsequent adverse events. There were no significant adverse side effects noted with adenosine.
Summary:
Low-dose adenosine is not effective in reducing adverse clinical events. Higher-dose adenosine may be beneficial in reducing adverse clinical events and infarct size, but these results need to be confirmed. Adenosine does not appear beneficial when reperfusion therapy fails or with delays of >2 to 4 hours after the onset of symptoms.
INTERACT (The INTegrelin and Enoxaparin Randomized assessment of Acute Coronary syndrome treatment Trial)
The Presenter:
Shaun Goodman, MD, St Michael’s Hospital, Toronto, Ontario, Canada
The Study:
A randomized, open-label trial conducted in Canada comparing the low-molecular-weight heparin enoxaparin (1 mg/kg subcutaneously, twice daily) with unfractionated heparin (UFH) (70 u/kg bolus, 15 u/kg/h, titrated to activated partial thromboplastin time 1.5 to 2xcontrol, per American College of Cardiology/American Heart Association guidelines) in 746 patients with acute coronary syndromes treated with aspirin and the glycoprotein IIb/IIIa antagonist eptifibatide. To qualify, patients had to have documented ST-segment changes (23%) and/or (+) biomarkers (80+%). The primary end point was safety assessed by major bleeding events (with the use of 2 separate classification criteria) at 96 hours. Secondary end points included ischemic events (by ST-segment monitoring) and clinical outcomes.
The Results:
Major bleeding (by use of a fall of 
3 g/dL hemoglobin) was significantly reduced with enoxaparin (1.8% versus 4.6% with UFH). With the use of a fall of 5 g/dL, the 2 groups were similar (0.27 with enoxaparin versus 0.79 with UFH). Minor bleeding events (including ecchymosis) were increased with enoxaparin. The mean time to angiography (performed in approximately two thirds of the patients) was 100 hours. PCI was performed in 27% to 30% of patients and CABG in 12% to 13%. The incidence of ischemic episodes with ECG monitoring was significantly reduced with enoxaparin, both within the initial 48 hours and from 48 to 96 hours. Clinical end points of death/myocardial infarction were also significantly reduced with enoxaparin (5% versus 9% with UFH).
Summary:
Enoxaparin seems superior to UFH in higher-risk patients with acute coronary syndromes treated with a glycoprotein IIb/IIIa antagonist and managed with a somewhat less-than-aggressive invasive management strategy. Major bleeding events are lower, ischemic episodes are fewer, and clinical outcomes are better.
WIZARD (Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders)
The Presenter:
Chris O’Connor, MD, Duke University, Durham, NC
The Study:
A randomized, placebo-controlled trial of azithromycin (600 mg daily for 3 days, then 600 mg a week for 11 weeks) in 7747 patients who were postmyocardial infarction (MI) with elevated titers to C pneumoniae. Patients who had undergone a revascularization procedure within the past 6 months were excluded. The primary end point was the composite of all-cause mortality, recurrent MI, revascularization, and hospitalization for angina. Patients were monitored for 2 years.
The Results:
There was no significant effect of azithromycin therapy on the primary outcome end points and no relationship between baseline C pneumoniae titers and outcome events. There were nonsignificant trends favoring azithromycin in men, patients with diabetes, and smokers. Despite a suggestion of possible early benefit, these differences were not sustained over the entire 2-year follow-up.
Summary:
Eleven weeks of azithromycin therapy does not affect clinical outcomes to 2 years in patients who were post-MI with elevated titers to C pneumoniae.
AZACS (AZithromycin in Acute Coronary Syndromes)
The Presenter:
Bojan Cercek, MD, Cedars Sinai Medical Center, Los Angeles, Calif
The Study:
A randomized, placebo-controlled trial of azithromycin (500 mg daily for 1 day, then 250 mg daily for 4 days) in 1400 patients with unstable angina or acute myocardial infarction (MI). There was no requirement at baseline for elevated C pneumoniae titers. The primary end point was the composite (at 6 months) of all-cause mortality, nonfatal MI, or recurrent ischemia requiring revascularization. Secondary end points included worsening ischemia requiring hospitalization, new congestive heart failure, or worsening congestive heart failure requiring hospitalization.
The Results:
There were no significant differences between groups in the primary end point or any of the secondary end points. There were also no differences between groups in subanalysis of patients with acute MI, or patients with elevated C pneumoniae titers.
Summary:
Short-term treatment with azithromycin in patients with unstable angina or acute MI did not improve clinical outcomes.
Revised Guidelines for Management of Patients With Non–ST-Segment Elevation Acute Coronary Syndromes
At the American College of Cardiology (ACC) meeting, the latest revisions of the ACC/American Heart Association (AHA) guidelines were announced (they can be found on the ACC and AHA web sites at http://www.acc.org or http://www.amheart.org). It has only been 18 months since the last iteration of these guidelines was published in September 2000; these, in turn, were the first revisions since 1994. Since September 2000, we have seen the results of GUSTO IV-ACS (Global Utilization of Streptokinase and TPA for Occluded arteries in Acute Coronary Syndromes), TACTICS/TIMI 18 (Treat angina with Aggrastat and determine Costs of Therapy with Invasive or Conservative Strategies), CURE (Clopidogrel in Unstable angina to prevent Recurrent ischemic Events), MIRACL (Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering), and other studies, and we need to adjust our "standards" accordingly.
The important changes in the new guidelines primarily relate to the initial medical management section of the document:
- Clopidogrel, largely on the basis of the results of the CURE trial, has a much more prominent role:
- in the initial medical therapy of conservatively managed patients (a Class I–level of evidence B recommendation in addition to aspirin).
- in those patients in whom a PCI is planned (again, a Class I–level of evidence B recommendation, though the exact timing of when it should be initiated is not addressed).
- in patients taking clopidogrel, in whom CABG is planned, the drug should be withheld for 5 to 7 days (a Class I–level of evidence B recommendation).
- The importance of glycoprotein (GP) IIb/IIIa inhibition in patients with non–ST-segment elevation acute coronary syndromes (ACS) has been modified:
- There is still a strong recommendation (Class I–level of evidence A) in patients with ACS in whom catheterization and PCI are planned, though the new guidelines now state that a GP IIb/IIIa antagonist may be administered in these patients just before PCI.
- In patients who have ongoing ischemia and are high risk but are not going to be treated with an early invasive strategy, the use of GP IIb/IIIa inhibitors has been downgraded:
Eptifibatide and tirofiban now carry a Class IIa–level of evidence A recommendation.
- Abciximab (on the basis of GUSTO IV) carries a Class III–level of evidence A recommendation (may be harmful).
- In patients without continuing ischemia and no other high-risk features in whom PCI is not planned:
- Eptifibatide and tirofiban carry a Class IIb–level of evidence A recommendation.
- Abciximab (again on the basis of GUSTO IV) carries a Class III–level of evidence A recommendation (may be harmful).
- The low-molecular-weight heparins have also been upgraded:
- Anticoagulation with subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin (in addition to aspirin and/or clopidogrel) carries a Class I–level of evidence A recommendation.
- Enoxaparin (specifically) is felt to be preferable to unfractionated heparin unless CABG is planned within 24 hours (a Class IIa–level of evidence A recommendation).
- The superiority of an early invasive management strategy (on the basis of TACTICS/TIMI 18) is emphasized in the management of higher-risk patients, now also including ST-segment depression and/or (+) biomarkers in addition to recurrent ischemia and other previously noted risk stratifiers (upgraded to a Class I–level of evidence A recommendation).
- With regard to longer-term therapy:
- Clopidogrel 75 mg/d upgraded as the alternative to aspirin in people who do not tolerate it (a Class I–level of evidence A recommendation).
- Combination therapy with aspirin/clopidogrel for 9 months after an ACS episode (a Class I–level of evidence B recommendation).
- An HMG-CoA reductase inhibitor and diet for LDL >100 mg/dL/L, begun 24 to 96 hours after admission, and continued at hospital discharge (a Class IIa–level of evidence B recommendation).
Electrophysiology
MADIT II (Multicenter Autonomic Defibrillator Implantation Trial II)
The Presenter:
Arthur Moss, MD, University of Rochester Medical Center, Rochester, NY
The Study:
A randomized, multicenter trial comparing implantable defibrillators (n=742) with conventional medical therapy (n=490) in patients with a history of prior myocardial infarction and a left ventricular ejection fraction 30%.2 Invasive electrophysiological testing was not required to qualify for the study. Patients were monitored for 4 years. The primary end point was all-cause mortality.
The Results:
At a mean follow-up of 20 months, all-cause mortality was 14.2% in the defibrillator group and 19.8% in the conventional medical therapy group (HR=0.69, 95% CI, 0.51 to 0.93, P=0.016). The benefits of defibrillator therapy were present across most major clinical subgroups stratified by age, sex, ejection fraction, NYHA class, and QRS duration.
Summary:
In patients with a history of prior myocardial infarction and a left ventricular ejection fraction 30%, there is significant survival benefit associated with prophylactic implantation of a defibrillator.
AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management)
The Presenter:
George Wyse, MD, PhD, University of Calgary, Alberta, Canada
The Study:
An National Heart, Lung and Blood Institute–sponsored trial conducted at 213 sites in the United States and Canada comparing rate versus rhythm control in patients with atrial fibrillation. A total of 4060 patients with documented atrial fibrillation (6 hours’, <6 months’ duration, with 1 risk factors for stroke) were randomized to rate control (digitalis, ß-blocker, Ca++ blocker, ablation, and pacing if necessary) or rhythm control (via a variety of pharmacologic agents, primarily amiodarone, sotalol, and propafenone, or nonpharmacological means). The primary end point was mortality.
The Results:
At 5-year follow-up, there were no differences between groups in mortality (rate control 21%; rhythm control 24%; P=0.058) or in composite cardiovascular events. The rate of subsequent hospitalization was slightly higher in the rhythm control group (78% versus 70% with rate control). The incidence of stroke tended to be slightly (but not significantly) higher in the rhythm control group (7.3% versus 5.7% with rate control). In both groups, the majority of strokes occurred after stopping warfarin, or with a subtherapeutic international normalized ratio. There were no differences between groups in functional status, quality of life, change in symptoms, or need for less anticoagulation.
Summary:
Rate control alone does provide acceptable outcomes, comparable with rhythm control. Regardless of treatment assignment, continuous anticoagulation is probably warranted in these patients.
RACE (RAte Control versus Electrical cardioversion for persistent atrial fibrillation)
The Presenters:
Harry Crijns, MD, University Hospital, Maastricht, the Netherlands; and Isabelle Van Gelder, MD, Interventional Cardiology Institute, Utrecht, the Netherlands
The Study:
A randomized, parallel group study comparing rate control with electrical cardioversion in patients with persistent atrial fibrillation. A total of 522 patients with atrial fibrillation >24 hours and <1 year and with 1 to 2 episodes of cardioversion in the past 2 years were randomized to rate control (to a heart rate <100 bpm) or rhythm control with electrical cardioversion and antiarrhythmic therapy. Rate control patients (with the exception of lone atrial fibrillation) were maintained on warfarin at an international normalized ratio 2 to 3.5x control; rhythm control patients were on warfarin for 1 month before and 1 month after cardioversion. Patients were monitored for 3 years. The primary end point was the composite of cardiovascular death, heart failure, thromboembolic complications, severe bleeding, pacemaker implantation, or severe adverse side effects of antiarrhythmic drugs. The study was designed as a noninferiority study with a noninferiority boundary of 10%.
The Results:
Primary outcome events were 17.2% in the rate control group and 22.6% in the rhythm control group; this met criteria for noninferiority. Hypertensive patients were noted to have an excess number of events with rhythm control.
Summary:
In patients with clinical persistent atrial fibrillation, outcomes are at least as good with rate control versus rhythm control therapy and may be superior in patients with hypertension.
InSynch ICD
The Presenter:
James B. Young, MD, Cleveland Clinic, Cleveland, Ohio
The Study:
A randomized, double-blind, controlled trial of biventricular pacing in 362 patients who otherwise required an implantable cardioverter-defibrillator (ICD). All patients had an active ICD implanted and were randomized to control (n=176) or biventricular pacing (n=186). Patients were monitored for 6 months. The primary end points were changes in quality of life (QOL, as documented by questionnaire), 6-minute walk distance, and NYHA class. Secondary end points included peak mVO2, total exercise time, and echocardiographic parameters.
The Results:
The biventricular pacing group had significant improvement in QOL score, NYHA class, and exercise time; peak mVO2 and maximal exercise time increased and echocardiographic LV volume decreased; 6-minute walk distance was not significantly improved. No adverse interactions were noted between biventricular pacing and ICD function.
Summary:
In patients who otherwise qualify for ICD implantation, the addition of biventricular pacing is associated with some improvement in clinical status and QOL, as well as improvement in peak mVO2 maximal exercise time and left ventricular volume, although 6-minute walk distance is not significantly improved.
Congestive Heart Failure
OVERTURE (Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events)
The Presenter:
Milton Packer, MD, Columbia-Presbyterian Medical Center, New York, NY
The Study:
A randomized, controlled trial comparing the vasopeptidase angiotensin-converting enzyme/neutral endopeptidase inhibitor omapatrilat (target dose 40 mg/d) with the angiotensin-converting enzyme inhibitor enalapril (target dose 20 mg/d) in 5780 patients with NYHA Class II through IV congestive heart failure (CHF) and ejection fractions 30% who had been hospitalized in the past year and were on diuretics. The primary end point of the study was the composite of all-cause mortality and hospitalization for CHF; 2 primary hypotheses (noninferiority versus enalapril and superiority versus enalapril) were tested.
The Results:
The incidence of primary outcome events was 33.7% in the enalapril group and 31.7% in the omapatrilat group (P=NS for superiority; significant for noninferiority). Similarly, all-cause mortality was not different between groups (17.6% with enalapril, 16.5% with omapatrilat). All major subgroups showed similar trends; there were no groups with particular benefit or harm. There was some benefit noted in the secondary composite end point of cardiovascular death and recurrent hospitalization (42.6% with enalapril, 40.8% with omapatrilat, P=0.024). The incidence of angioedema with omapatrilat was very low (0.8%).
Summary:
Omapatrilat (up to 20 mg/d), although well tolerated in a CHF population, does not provide significant benefit over enalapril (up to 40 mg/d) in terms of all-cause mortality and repeat hospitalization for CHF.
ENABLE 1 and 2 (ENdothelin Antagonist Bosentan for Lowering cardiac Events in heart failure)
The Presenter:
Milton Packer, MD, Columbia Presbyterian Medical Center, New York, NY
The Study:
An investigational program consisting of 2 studies: ENABLE 1 (conducted in Europe and Australia) and ENABLE 2 (conducted in North America). A total of 1613 patients with severe congestive heart failure (NYHA Class III or IV) were randomized to either bosentan (an endothelin antagonist; 62.5 mg twice daily for 4 weeks, then 125 mg twice daily) or placebo, in addition to diuretics, angiotensin-converting enzyme inhibitors, ß-blockers, and other standard therapies. Approximately two thirds of the patients had ischemic cardiomyopathy. The primary end point was the combined incidence of death or congestive heart failure hospitalization.
The Results:
There were no significant differences between groups in primary outcome events (321 of 808 with placebo versus 312 of 805 with bosentan) or all-cause mortality (173 of 808 with placebo versus 160 of 805 with bosentan). There appeared to be an early (within the first 2 to 4 weeks) hazard for repeat hospitalization in the bosentan group. Patients on bosentan were also noted to have more fluid retention (as manifested by increases in weight and peripheral edema and decreases in hemoglobin).
Summary:
In patients with severe congestive heart failure, bosentan (62.5 mg twice daily for 4 weeks, then 125 mg twice daily) was associated with more fluid retention and no improvement in clinical outcomes or all-cause mortality.
BNP (Breathing Not Properly)
The Presenter:
Alan S. Maisel, MD, San Diego VA Healthcare Center and University of California at San Diego, San Diego, Calif
The Study:
A prospective blinded study of a bedside brain natriuretic peptide (BNP) test in patients presenting to the emergency room with dyspnea. Qualifying patients had BNP levels checked and were examined by physicians blinded to the BNP results. A total of 744 patients were ultimately given the diagnosis of heart failure and 770 had a non–heart failure diagnosis made.
The Results:
A BNP cutoff of <100 pg/mL had a sensitivity of 90%, a specificity of 74%, and a diagnostic accuracy of 81% for identifying the presence of heart failure. In comparison, blinded clinical assessment yielded a diagnostic accuracy of 74%, but evaluating physicians indicated they were unsure 43% of the time. The level of BNP was also correlated with NYHA functional class.
Summary:
In patients presenting with dyspnea, the use of a bedside BNP measurement significantly improves the diagnostic certainty of identifying patients with congestive heart failure, beyond that of symptoms, baseline characteristics, and clinical history.
HARDBALL (Heart Allograft Rejection: Detection with Breath Alkanes in Low Levels)
The Presenter:
Michael Phillips, MD, Menssana Research Inc, Fort Lee, NJ; and NY Medical College, Valhalla, NY
The Study:
An evaluation of a breath collection analyzer that measures the presence of volatile organic compounds (VOCs) such as pentane in exhaled gases expressed as the breath methylated alkane contour (BMAC). It was hypothesized that conditions causing myocardial oxidative stress, such as transplant rejection, will alter the BMAC. The test was evaluated in 539 heart transplant recipients and 32 healthy volunteers.
The Results:
Different patterns of VOCs were detected in normal volunteers and in patients with class 0 to 2B rejection (confirmed by biopsy). Patients with class 3A+ rejection were more similar to normals, perhaps because high levels of alkanes in the breath may induce their own metabolism. Although the positive predictive value of BCA was low (5.7% versus 37% with biopsy), the negative predictive value was very good (97.3% versus 97.5% with biopsy). The authors noted that the BMAC could also be affected by other conditions causing oxidative stress, such as infection.
Summary:
The BMAC test is an interesting potential screening test for evaluating the presence of acute severe rejection; it appears to be as sensitive as endomyocardial biopsy in excluding the presence of severe rejection. How it may be integrated into standard practices will require further study.
Interventional Cardiology
LIPS (Lescol Intervention Prevention Study)
The Presenter:
Patrick Serruys, MD, PhD, Thoraxcentrum, Rotterdam, the Netherlands
The Study:
A randomized, blinded, placebo-controlled trial of the HMG CoA reductase inhibitor fluvastatin in 1677 patients undergoing first-time PCI of a native vessel who were randomized to either fluvastatin (40 mg twice daily) or placebo, with the first dose given an average of 2.7 days after successful PCI of one or more lesions and continued for 3 to 4 years. The primary end point was the composite incidence of cardiac deaths (deaths were assumed to be cardiac unless specifically otherwise noted), myocardial infarction, or repeat revascularization (PCI or CABG). Patients on prior lipid-lowering therapy were excluded, and patients had to have total cholesterol of 135 to 270 mg/dL to qualify for the study.
The Results:
The mean baseline LDL was 132 mg/dL. The incidence of primary adverse events was significantly reduced in the fluvastatin group, with a 22% relative reduction (from 26.7% to 21.4%) in events over the follow-up period, with similar trends in all of the individual major adverse cardiac event components. Particular benefit was noted in the subgroup of patients with diabetes (from 37.8% to 21.7%) and patients with multivessel disease (from 33.9% to 23.0%). Fluvastatin was very well tolerated, with no episodes of rhabdomyolysis.
Summary:
The use of fluvastatin significantly decreases the incidence of major adverse clinical events over 3 to 4 years after PCI. There is particular benefit in patients with diabetes and/or multivessel disease.
ISAR-STEREO 2 (Intracoronary Stenting and Angiographic Results—Strut Thickness Effect on REstenosis Outcome)
The Presenter:
Helmut Schühlen, MD, Deutsches Herzzentrum, Munich, Germany
The Study:
A randomized trial conducted in 4 hospitals in Germany comparing the outcomes of thinner-strut stents (50 µm, Guidant ACS Rx MultiLink) with thicker-strut stents (140 µm, Cordis BX-Velocity) when used for PCI of native coronary vessels 2.8 mm. A total of 611 patients were randomized to receive 1 of the 2 stents; follow-up angiography was performed at 6 months, and clinical follow-up at 1 year. The primary end point was the incidence of >50% stenosis within the stent at follow-up angiography. Secondary end points included clinical restenosis (target vessel revascularization) and the combined incidence of death or myocardial infarction at 1 year.
The Results:
Procedural success was similar between groups; device success was significantly lower in the thin-strut group (87.6% versus 98.7%, P<0.001). Acute angiographic results (minimal lumen diameter) were very similar between groups. At follow-up angiography, the thin-strut group had a significantly greater minimal lumen diameter (1.96 versus 1.70 mm, P=0.006), significantly less late loss (0.93 versus 1.19 mm, P<0.001), significantly lower loss index (0.51 versus 0.65, P<0.001), and a significantly lower incidence of the primary restenosis end point (17.9% versus 31.4, P=0.002) and target vessel revascularization (12.3% versus 21.9%, P=0.002). No difference was noted in the combined rate of death/myocardial infarction at 1 year (4.9% versus 6.3%, P=NS).
Summary:
Stent strut thickness is significantly related to subsequent restenosis; thinner struts are associated with less restenosis. This effect appears to be independent of stent design.
COAST (heparin-COAted STents in small coronary arteries)
The Presenter:
Michael Haude, MD, University of Essen, Essen, Germany
The Study:
A randomized, controlled trial conducted in 21 clinical centers in Europe comparing the use of heparin-coated stents, noncoated stents, and balloon angioplasty in 605 patients undergoing PCI of small (2.0 to 2.6 mm) coronary arteries. The primary end point was the minimal lumen diameter at 6 months.
The Results:
Acute postprocedural lumen gain was greater in 2 stent groups. Procedural success was 73% with balloon angioplasty, 98% with a bare stent, and 98% with a coated stent; 27% of the balloon angioplasty patients crossed over to stent implantation for suboptimal results. Although minimal lumen diameter at 6 months was greater in the 2 stent groups, the incidence of binary restenosis at follow-up angiography was 32% in the balloon angioplasty group (including crossover), 25% in the bare stent group, and 30% in the coated stent group (P=NS). Overall event-free survival was similar between groups.
Summary:
In lesions in small coronary arteries, stenting gives a better angiographic appearance, but restenosis and clinical events are no different from balloon angioplasty alone. Heparin coating on stents did not appear to provide any additional benefit.
AMIGO (Atherectomy before Multilink stenting Improves lumen Gain Outcome)
The Presenter:
Antonio Columbo, MD, Milan, Italy, Lenox Hill Hospital, New York, NY
The Study:
A multicenter, randomized trial comparing prestent atherectomy debulking to stenting alone in patients undergoing coronary intervention. A total of 753 patients at 37 US and 6 European clinical centers undergoing PCI of de novo or restenotic lesions were randomized to stenting alone or directional atherectomy followed by stenting. The primary end point was the incidence of binary restenosis on follow-up angiography at 8 months.
The Results:
Although the initial angiographic results appeared better in the atherectomy plus stent group, the incidence of restenosis at follow-up angiography (performed in 75% of the patients) was 22.1% in the stent alone group and 26.9% in the atherectomy plus stent group (P=NS). "Optimal" atherectomy results were only achieved in 21.5% of patients. In patients who did achieve optimal atherectomy results (n=68), the restenosis rate tended to be somewhat lower (16.2%).
Summary:
A debulking strategy with the use of directional coronary atherectomy before stent implantation did not result in a significant reduction in angiographic restenosis. Optimal atherectomy results were only obtained in one fifth of patients.
References
1. Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002; 359: 995–1003.[CrossRef][Medline] [Order article via Infotrieve]
2. Moss AJ, Zareba W, Hall WJ, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. New Engl J Med. 2002; 346: 877–883.
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