From This Week’s Issue of Circulation: Breast-Feeding May Reduce Later Blood Pressure
Mothers who breast-feed their babies today may be lowering their children’s blood pressure later, said researchers in a report in this week’s issue of the journal Circulation (Circulation. 2004;109:1259–1266OpenUrl).
Richard M. Martin, MSc, MFPH, and colleagues from the Division of Child Health at the University of Bristol in Britain examined 7276 singleton 71/2-year-old children born at term in 1991 and 1992. Complete data were available for 4763 of the children. The blood pressures of the children who had been breast-fed were, on average, 1.2 mm Hg lower than those of children who had never been breast-fed. The differences decreased but remained statistically significant in models that controlled for social, economic, maternal, and physical characteristics. The differences were the same whether the breast-feeding was done part-time or exclusively. The researchers found that for every 3 months of breast-feeding, the children had a 0.2-mm Hg reduction in systolic blood pressure.
“Even this small reduction may have important population-health implications, because an increased mortality risk is observed across the blood pressure distribution and not just above threshold levels. A 1% reduction in population systolic blood pressure levels is associated with an 1.5% reduction in all-cause mortality, equivalent to a lessening in premature mortality of 8000 and 2000 deaths per year in the United States and United Kingdom, respectively . . . the wider promotion of breast-feeding is a potential component of the public health strategy to reduce population levels of blood pressure,” the researchers wrote.
From the 2004 Scientific Sessions of the American College of Cardiology
NEW ORLEANS, La—Red dresses, the First Lady, and a look at everything from stents to surgery to the latest in drugs headlined the 2004 Scientific Sessions of the American College of Cardiology (ACC), March 7–10, 2004, in the Big Easy.
First Lady Laura Bush made an appearance during the Presidential Plenary on March 8, 2004, amid heightened security. Most of the 4-day conference, however, was dedicated to the latest in cardiology, and in particular, the late-breaking clinical trials, which generated considerable interest.
A Direct Approach
Direct stenting with the sirolimus-eluting stent was as good as and, in some cases, better than dilating the artery with a balloon first and then deploying the drug-eluting stent, said Jeffrey Moses, MD, of Lenox Hill Heart and Vascular Institute in New York City.
Previously, direct stenting had been discouraged because of fears that the polymer coating on the stent would be disrupted, resulting in drug loss, he said during the Late-Breaking Clinical Trials in Interventional Cardiology session on March 7, 2004.
In this study, he and his colleagues in the multicenter trial attempted to place the stent directly in 225 patients and compared their results with those of 412 patients (historical controls) who underwent pre-stent dilatation by angioplasty and then received the drug-eluting stent. The restenosis rate was the same in both groups, said Dr Moses.
“This shows us that direct stenting can further improve outcomes with this revolutionary technology,” said Dr Moses. “Direct stenting was not inferior at all endpoints assessed, when compared to predilatation strategy.”
John Hodgson, MD, of Cleveland, who was the session chair, noted the greater stent-to-lesion length in the trial led by Moses and suggested that it may have had an effect. Dr Moses said that because data were still being analyzed, that information cannot be determined as yet.
An Answer to Small Coronary Arteries
Sirolimus-eluting stents reduce restenosis and major adverse cardiac events in very small coronary arteries occluded with atherosclerotic lesions, said Diego Ardissino, MD, of the Università Degli Studi di Parma, in Parma, Italy, during the Late-Breaking Clinical Trials in Interventional Cardiology session March 7, 2004, at ACC Scientific Sessions 2004. “They represent a means to revascularize small coronary arteries effectively.”
In the SES-SMART study (Sirolimus-Eluting Stents in Small Arteries), investigators enrolled 129 patients in the drug-eluting stent arm of the study and 128 in the arm of the study that included a bare metal stent of the same architecture. All patients had documented non–ST-segment–elevation acute coronary syndrome or silent myocardial ischemia and a de novo lesion in the coronary vessels of less than 2.5 mm.
At 8 months, the binary restenosis rate was 53.1% in the bare stent group and 9.8% in the drug-eluting stent group. Clinical events were lower in the drug-eluting stent group than in the bare metal stent group.
Czech It Out—Patency Same After On-Pump and Off-Pump Coronary Artery Bypass Surgery
After one year, coronary artery grafts using the left internal mammary artery were the same, whether the surgery had been performed off-pump or on-pump, said Petr Widimsky, MD, of the Cardiocenter Vinhorady in Prague, Czechoslovakia. Grafts using saphenous veins had lower patency, but they were similar, with a trend toward higher patency in on-pump patients, he said.
There was also no difference in deaths, myocardial infarctions, stroke, or the need for new revascularization, said Dr Widimsky.
In this single-center trial, 192 consecutive patients were randomly assigned to the on-pump group and 208 patients to off-pump surgery. A total of 184 patients in the on-pump group underwent surgery, and 204 in the off-pump group had an operation; 203 received on-pump surgery, and 185 received off-pump surgery.
One-year follow-up by coronary angiography in 132 on-pump patients and 123 off-pump patients demonstrated graft patency of 91% of left internal mammary artery grafts in both off-pump and on-pump patients. Patency at one year was 59% in the on-pump patients and 49% in the off-pump patients who received a saphenous vein graft.
The “beating-heart” technique was applicable in 84% of the consecutive patients who were assigned to that group, said Dr Widimsky.
ARCHeR Takes Aim at Carotid Artery Disease
In a series of 3 clinical trials called ARCHeR (ACCULINK for Revascularization of Carotids in High-Risk Patients), the use of a carotid stent (ACCULINK) and a device designed to trap clots and other debris from atherosclerotic plaque (ACCUNET and RX ACCUNET) that might be dislodged during the procedure appeared to be an effective treatment for high-risk patients for whom carotid endarterectomy was not possible. (ACCULINK, ACCUNET, and RX ACCUNET are made by Guidant Corp.)
“I think for high-risk patients, when these devices are approved, we should see a rapid transition to stenting,” said William Gray, MD, of Swedish Medical Center in Seattle, Washington. He said he expected that adoption of the technique in low-risk patients will be slower, although patients will choose the nonsurgical technique if given the option.
Researchers enrolled 158 patients in ARCHeR 1, 278 in ARCHeR 2, and 145 in ARCHeR 3. ARCHeR 1 involved delivery of the stent alone. ARCHeR 2 involved stent delivery with the capture device. ARCHeR 3 researchers used the RX ACCUNET, an improved trapping device. Results were compared to historical controls.
Thirty-day event rates were virtually the same in ARCHeR 1 and 2. Mortality rates were 2.5% in ARCHeR 1 and 2.2% in ARCHeR 2. Stroke rates were 4.4% and 5.8% in ARCHeR 1 and ARCHeR 2, respectively; myocardial infarction rates were 2.5% and 2.9%. The composite end point of death, stroke, or myocardial infarction was 8.6% in ARCHeR 2 and 8.3% in ARCHeR 3. The need for target-vessel revascularization was 2.2% in ARCHeR 1 and 2.8% in ARCHeR, demonstrating that the treatment was durable, said Dr Gray.
However, the use of the trapping device did not appear to make a difference, said Dr Gray. Minor strokes that occurred had no clinical significance at 1 year. Carotid stenting with embolic protection appeared to have success rates comparable with carotid endarterectomy, he said.
When Dr Hodgson asked why the strokes continued to occur, Dr Gray said, “We are still in the early phase of evolution of these devices. In 4% to 5% of patients, we could not get the filters delivered. That may make a difference.”
Transplanting Myocytes Without Surgery
Building on prior experience with transplanting myocytes during coronary artery bypass grafting, Tomasz Siminiak, MD, of the University School of Medical Sciences, the Institute of Human Genetics, Polish Academy of Sciences in Poznan, Poland, is now implanting the cells percutaneously.
“Since the previous studies were done with the bypass, it was not possible to distinguish the effects from the revascularization,” said Dr Siminiak. “Therefore, we started this phase I clinical trial to evaluate the efficacy and safety of myoblast transplant by the percutaneous approach.”
Ten patients with post–myocardial infarction heart failure were enrolled in the trial, which used a catheter system and intravenous ultrasound to find the proper spot and perform the injections into the myocardium. The procedure was completed in 9 of the patients.
Two to four intramyocardial channels that were 1.5 to 4.5 cm deep were used to implant the cells. As many as 107 cells were delivered to the site. Nine patients were on amiodarone and did not experience arrhythmia, said Dr Siminiak. An instance of ventricular tachycardia appeared in the 1 patient not on amiodarone who had an implanted defibrillator.
Dr Siminiak said he saw ejection fraction improvement in 4 of the 6 patients who could be evaluated after 6 months. There was improvement in New York Heart Association class in all cases, he said.
“Percutaneous myoblast transplantation with this novel technique is safe and feasible,” he said. “Phase II and III trials are needed to assess the efficacy” of the treatment.
Although the use of CALDARET made no significant difference in infarct size in the total population of patients with ST-elevation myocardial infarction who underwent primary percutaneous intervention, it did appear to have an effect in patients who had had an anterior infarction, said Dan Tzvoni, MD, of Shaare Zedeck Medical Center in Jerusalem. His presentation took place during the Late-Breaking Clinical Trials on Novel Therapies for Acute Myocardial Infarction session at the annual Scientific Sessions of the ACC on March 7, 2004. He said that US trials using high doses of the drug will demonstrate a large difference in this population.
His study enrolled 387 patients from 5 countries. Patients were randomly assigned to receive CALDARET at 57.5 mg or 172.5 mg or placebo. “All cardiac enzymes were better in patients on high-dose CALDARET,” said Dr Tzvoni.
He noted that the results with the drug are preliminary, but he said the drug could become an integral part of treatment for patients who require emergency reperfusion after acute myocardial infarction.
CAPITALizing on Two Treatments
Using a thrombolytic treatment (tenecteplase) before transferring a patient to the catheter lab appeared to have an advantage over tenecteplase alone, said Michael LeMay, MD, from the University of Ottawa, in a presentation during the Late-Breaking Clinical Trials on Novel Therapies for Acute Myocardial Infarction session on March 7, 2004.
He and his colleagues from 4 Ottawa hospitals enrolled 170 acute myocardial infarction patients into the CAPITAL AMI (Combined Angioplasty Pharmacological Intervention versus Thrombolytics Alone in Acute Myocardial Infarction) study. Of these, 86 received the combined therapy, and 84 received only tenecteplase.
“All patients got TNK-tPA [tenecteplase] full dose with unfractionated heparin in a weight-adjusted infusion,” said Dr LeMay. “There was a significant reduction in favor of the combination treatment in the composite endpoint of mortality, recurrent myocardial infarction, recurrent unstable ischemia, or stroke at 30 days. The endpoint occurred in 21.4% of patients in the drug-only group and 9.3% in the combination treatment group.”
Neither the difference in deaths nor the reinfarction rate was statistically significant. Recurrent unstable ischemia did show a statistically significant difference at 30 days, he said. He said the combination was clearly better in high-risk patients with ST-segment–elevation myocardial infarction.
The Sheen off EMERALD
Distal embolization does not appear to play a major role in preventing revascularization in small blood vessels, said Bruce Brodie, MD, of Moses Cone Heart and Vascular Center, LeBauer Cardiovascular Research Foundation, in Greensboro, NC. He described the EMERALD (Enhanced Myocardial Efficacy and Recovery by Aspiration of Liberalized Debris) trial during a Late-Breaking Clinical Trials on Novel Therapies for Acute Myocardial Infarction session at the annual Scientific Sessions of the ACC.
In an attempt to improve blood flow in small arteries, Dr Brodie and his colleagues enrolled 427 patients with ST-segment–elevation myocardial infarction in the study. Half the patients received percutaneous intervention with a guardwire that prevented clots and other material from going downstream. The guardwire involved inflating the balloon on the wire in an area where there was little blood flow and deploying a stent. Then, an export catheter was used to aspirate the debris. The physician then let the balloon down and removed the guidewire.
There was no difference in the measurements of microcirculation and no difference in infarct size, said Dr Brodie. “We were able to get material out of the arteries in more than 70% of patients. The guardwire can be used in patients with acute myocardial infarction safely, and it can retrieve clot and atheroma debris. It did not alter micro vascular reperfusion,” he said.
“The big question is where to go from here,” he said. Investigators of similar studies will now attempt to determine whether they should continue the study, but “it doesn’t look promising.”
Consider It PROVEd
The message from PROVE-IT 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy—Thrombolysis in Myocardial Infarction 22) is that intensive lipid-lowering substantially benefited patients recently hospitalized with acute coronary syndrome, said Christopher Cannon, MD, of the Brigham and Women’s Hospital in Boston, Mass, speaking on behalf of his fellow investigators at a Late-Breaking Clinical Trials session of the ACC 2004 Scientific Sessions.
“Beginning today, we have evidence that patients going home from the hospital need to be treated early and intensively with lipid-lowering therapy. In this trial, lowering low-density lipoprotein cholesterol (LDL-C) benefited acute coronary syndrome patients, especially those with a higher baseline LDL,” he said. “The guidelines need to be updated for this high-risk group of patients.”
In the study, 4161 patients who had been hospitalized with acute coronary syndrome were randomized within 10 days to receive two different intensities of lipid-lowering. One group received 40 mg of pravastatin and the other 80 mg of atorvastatin. The groups were monitored for 2 years. At the end of the study, 26.3% of patients in the pravastatin group and 22.4% in the atorvastatin group had reached one of the primary end points (death from any cause, myocardial infarction, unstable angina requiring rehospitalization, revascularization 30 days or more after randomization, and stroke). This reflects a 16% reduction in the hazard ratio in favor of atorvastatin, Dr Cannon said.
“The benefit started early on and continued throughout the 21/2-year treatment period. It was the same in all basic subgroups,” Dr Cannon said. The greatest benefit was seen among patients with an LDL-C above 125 mg/dL. The average LDL-C of patients in the intensive statin therapy group was 62 mg/dL. The average for those in standard lipid-lowering therapy group was 95 mg/dL.
A report of the trial was released early online March 8, 2004, by The New England Journal of Medicine at http://content.nejm.org/cgi/content/abstract/NEJMoa040583. It will appear in the print version of the journal April 8, 2004.
Good News About Defibrillators, Bad for Amiodarone
Implantable defibrillators save the lives of patients with common heart failure, said Gust H. Bardy, MD, of the University of Washington Medical Center, as he described the SCD HeFT (Sudden Cardiac Death Heart Failure Trial) in a late-breaker session of the ACC’s 2004 Scientific Sessions.
A total of 2521 patients was enrolled at 148 centers in North America and New Zealand, said Dr Bardy. The trial’s goal was to determine whether amiodarone or a conservatively programmed shock-only implantable cardiac defibrillator would reduce all-cause mortality in patients. The patients had ischemic or nonischemic heart failure, were in New York Heart Association class II or II, and had an ejection fraction equal to or less than 35%.
Patients were on optimal medical therapy, he said. Although the amiodarone group did no better than the group that received placebo, there was a 23% reduction in all-cause mortality in the implantable defibrillator group.
“Implantable defibrillators save lives,” said Dr. Bardy. “If this were a drug therapy, it would be readily embraced, but it’s a machine with an expensive price tag. People tend to be more tentative about embracing it. Look at the numbers. They speak volumes.”
He said the trial was designed to represent the middle segment of people who have heart failure in order to provide important answers about their treatment. “The study was designed to cover large numbers of people and to discuss simple therapies for broad segments of the US population.”
Study Not “DINAMIT” for Defibrillators
Implanting a defibrillator early after a patient has been hospitalized with an acute myocardial infarction does not prevent further cardiac-related deaths, although it does reduce deaths from arrhythmia, said Stefan Hohnloser, MD, of the J.W. Goethe–University College in Frankfurt, Germany, at a late-breaking clinical trials session of the ACC 2004 Scientific Sessions. The trial was called DINAMIT (Defibrillator IN Acute Myocardial Infarction Trial).
A total of 674 patients who had had a myocardial infarction 4 to 40 days previously, were between 18 and 80 years of age, and had an ejection fraction of 35% or less were enrolled in the trial. Of those, 332 patients were in the implanted defibrillator arm of the study, and 342 were in the medical therapy arm. Heart failure in the study was optimal, with patients receiving recommended medications in the vast majority of cases. Patients were monitored, on average, for 30 months.
The primary end point of the study was all-cause mortality, and an important secondary end point was arrhythmic death. “The defibrillator does prevent arrhythmic deaths. That’s what it’s built to do,” said Dr Hohnloser. The relative risk reduction in arrhythmic deaths between the 2 groups was 58%.
“However, the beneficial effect of the defibrillator was offset by an unexpected increase in non-arrhythmic deaths,” said Dr Hohnloser. “The principal mode of death in the non-arrhythmic deaths was still cardiovascular.”
“We could see no benefit in all-cause mortality by selecting patients for the defibrillator therapy in the first 4 weeks after the myocardial infarction,” he said. “I would suggest you have to wait until everything is stabilized.”
PAVE-ing the Way for Biventricular Pacing
Biventricular pacing provides sustained benefit to patients with chronic atrial fibrillation who have undergone atrioventricular nodal ablation, said Rahul Doshi, MD, of Sunrise Hospital and Medical Center in Las Vegas, Nevada, during a late-breaking clinical trials session of the ACC Scientific Sessions 2004.
As he described the PAVE (Post AV Nodal Ablation Evaluation) study, Dr Doshi said, “This is a disease of the elderly with a high prevalence. There are now 30 000 patients like this each year, and it is expected to double” within the next decade.
The study leaders randomized patients to biventricular pacing or right ventricle pacing. In the biventricular arm, 102 patients were evaluable; 82 were evaluable in the right ventricle arm.
The patients in the biventricular arm of the study improved their 6-minute walk time by 26 meters, said Dr Doshi. (A 6-minute walk time was the primary end point of the study.) The peak Vo2 measurement stayed the same between measurement at 6 weeks and measurement at 6 months. However, the measurement in the biventricular group increased by 1.02 mL/kg per minute at 6 months.
An interesting measurement was that of left ventricular ejection fraction, said Dr Doshi. At baseline, the ejection fraction was 45% at baseline for both groups. At 6 months, the ejection fraction for the biventricular pacing group had remained the same, but it had deteriorated to approximately 40% in the right-ventricle pacing group.
“We conclude that for our patients with chronic atrial fibrillation who have undergone AV [atrioventricular] nodal ablation, biventricular pacing produces statistically significant improvement in functional capacity over right ventricular pacing,” he said. “It reflects a sustained benefit in the biventricular group.”
ALLIANCE Improves Health
Intensive treatment to reduce low-density lipoprotein cholesterol (LDL-C) levels reduced deaths and other major cardiovascular-related events in a group of patients recruited from managed care and veterans hospitals, said Donald B. Hunninghake, MD, of the University of Minnesota in Minneapolis.
Unlike the PROVE-IT study, his trial compared intensive treatment with atorvastatin to usual treatment, which in some cases included diet, lifestyle changes, or lipid-lowering drugs. The ALLIANCE (Aggressive Lipid-Lowering Initiation Abates New Cardiac Events) trial enrolled 2442 patients with heart disease. Roughly half were randomized to the atorvastatin group and half to usual care. Patients were over the age of 18, with a history of coronary heart disease and an LDL-C greater than 130 mg/dL.
“Usual care is the lipid treatment program prescribed by the patient’s primary physician and could include diet, behavior modification, and antihyperlipidemic medications, including atorvastatin after 1997 (when it was approved),” said Dr Hunninghake.
Patients on the statin began at 10 mg daily and were titrated until they achieved an LDL-C of 80 mg/dL or 80 mg of drug per day, he said. Use of other lipid-lowering drugs was not permitted. At the beginning of the trial, the average LDL-C in both groups was 147 mg/dL. By the end, the atorvastatin group had reached 95 mg/dL and usual-care group 111 mg/dL.
The atorvastatin group achieved a 17% reduction in the combined end point of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and stroke, said Dr Hunninghake. There was a 47% percent reduction in nonfatal heart attacks in the atorvastatin group, he said.
“Part of the rationale for our trial was to show more aggressive control of LDL-C results in more benefit,” said Dr Hunninghake. For that reason, he said, the researchers decided to do the trial in a usual clinical setting.
A New Anti-Fat Drug in the City of Mardi Gras (Fat Tuesday)
An as-yet unapproved drug promises to aid in two of the most critical and difficult lifestyle changes: losing weight and stopping smoking. Two trials described at a late-breaking clinical trials session of the ACC Scientific Sessions 2004 demonstrated that rimonabant (Acomplia) achieves new targets in the ongoing battle against cigarettes and obesity with few side effects.
“Rimonabant, at the 20-mg dose, doubled the chance of quitting smoking,” said Robert Anthenelli, MD, of the University of Cincinnati (Ohio) College of Medicine. It also reduced the weight gain that usually accompanies smoking cessation, he said.
In STRATUS-US (Studies with Rimonabant And Tobacco Use), researchers enrolled 787 smokers in a double-blind placebo-controlled trial conducted at 11 sites in the United States. On average, subjects smoked 23 cigarettes per day. They were randomly assigned to receive 5 mg rimonabant, 20 mg rimonabant, or placebo daily. During the 10-week trial, smoking continued for the first 2 weeks. On day 15, they stopped. They reported whether or not they continued to smoke, and researchers measured exhaled CO and plasma cutinize, the principal nicotine metabolite, to determine whether or not they continued to smoke.
Rimonabant at the 20-mg dose doubled the chance that an individual would quit smoking, the researchers said. As an added benefit, it “has the potential to reverse post-cessation weight gain that’s an obstacle for people who quit smoking,” said Dr Anthenelli. Patients in the placebo group gained an average of 3.7 kg over the period they quit smoking. By contrast, people in the 20-mg rimonabant group gained an average of 0.6 kg, and some even lost weight.
In the companion trial RIO-Lipids (Rimonabant in Obesity), the one third of the 1036 patients in the trial taking 20 mg of drug daily lost an average of 8.6 kg over a year, compared with a loss of only 2.3 kg in the placebo group, said Jean-Pierre Despres, PhD, of Laval University and director of research for cardiology at the Laval Hospital Research Center in Quebec. (Patients in the 5-mg group demonstrated little effect.)
“The results of this trial may indicate that physicians have a new tool to treat obesity,” he said. The study targeted visceral obesity because of its relationship to cardiovascular disease.
Patients in the study had a body mass index (BMI) between 27 and 40 kg/m2, said Dr Despres. More than 72% of patients on the 20-mg dose of rimonabant lost at least 5% of their body weight, compared with 41.8% of the patients in the 5-mg group and 27.6% of patients in the placebo group.
Not only did rimonabant at the 20-mg level decrease weight, it also reduced waist circumference by about 9 cm, increased high-density lipoprotein cholesterol levels by 23%, reduced the size of low-density lipoprotein cholesterol particles, and decreased levels of C-reactive protein. The drug was well tolerated, he said. The most common side effects were gastrointestinal, particularly nausea.
Rimonabant was born out of the observation that people who smoked marijuana invariably developed the “munchies.” Scientists studying the phenomenon identified what they called the endocannabinoid system, believed to play a role in regulating body weight, lipid metabolism, and tobacco dependence. Nicotine in cigarettes gets the system out of balance, as does eating too much and developing loads of fat.
“This is a new drug with a new mechanism of action that targets cardiovascular risk factors,” said Dr Despres. “It is the first medication that could be used to treat tobacco use and overweight and obesity and make major inroads in preventing cardiovascular disease.”
Myocytes to Heart Appear Safe
Clinical trials in which myoblasts are taken from skeletal muscle tissue, expanded in the laboratory, and transplanted into the heart during bypass graft surgery are warranted after the first 22 patients proved the safety of the procedure, said Nabil Dib, MD, of the Arizona Heart Institute in Phoenix, at a late-breaking session of the ACC Scientific Sessions 2004.
The phase-1, open-label, nonrandomized, multicenter clinical trial was initially approved by the US Food and Drug Administration to study 12 subjects, but the agency later expanded the number of patients to 22. In the first group, ejection fraction was less than 30%. The second group could include patients with an ejection fraction of less than 40%.
Patients, who received from 10 million to 300 million cells, were subjected to extensive follow-up for an average of 18 months, said Dr Dib. “These were very sick patients,” he said.
There were some indications that the treatment was effective, he said. Positron emission tomographic scans showed that scar tissue had become viable in many instances within 6 months of the treatment. One patient in the study sustained a blood clot in the graft to the right coronary artery, said Dr Dib. Two patients had transient period of ventricular tachycardia.
“The findings are encouraging enough to proceed with larger clinical trials,” he said.
A trial that was ended prematurely by the Veterans Affairs Administration and that suffered from poor recruitment failed to answer its primary question: Which drug is superior in preventing vascular events—aspirin, clopidogrel, or warfarin? The WATCH (Warfarin and Antiplatelet Trial in Chronic Heart Failure) study leaders changed the end point and had recruited only 40% of the subjects for which they had planned when the Veterans Affairs Administration ended the study early. The results were presented during a late-breaking clinical trials session of the ACC Scientific Sessions 2004.
To increase the study’s power, the researchers decided to focus on warfarin versus aspirin and clopidogrel versus aspirin. A total of 1587 patients had been enrolled, and mean follow-up was 23 months.
Nonfatal myocardial infarction was slightly less frequent in the aspirin group, and nonfatal stroke was considerably lower in the warfarin group. The numbers for aspirin versus clopidogrel were virtually the same. There was no significant difference among end points, said Barry Massie, MD, of the San Francisco Veterans Affairs Medical Center.
There was an indication of fewer hospitalizations in the warfarin group, said Dr Massie. That finding is not unexpected, he said. “Some experts don’t think aspirin should be routinely used in heart failure patients,” he said. “You should consider something else in these people.”
He expressed disappointment that the study did not reach the needed power. “It is difficult to make a strong recommendation based on a study with unresolved questions,” he said.
Everest I: Clipping Mitral Valve Regurgitation Down To Size
A percutaneous method of repairing mitral valves appears ready for larger trials, said a lead researcher in EVEREST I (Endovascular Valve Edge-to-Edge Repair Study) at a late-breaking clinical trials session at the ACC Scientific Sessions 2004. Ted Feldman, MD, of Evanston Northwestern Healthcare in Illinois, said the repair technique uses a small clip made of surgical alloys and covered in a polyester material to clip to the valve’s leaflets and create a double orifice to alleviate mitral valve regurgitation.
Twenty patients have been treated with the investigational device so far, said Dr Feldman. Most were older, male, and had a variety of comorbidities. He reported on the outcome in the first 10.
The clip was deployed using a percutaneous method, resulting in substantial reduction of regurgitation in 7 patients. In one patient, the clip detached. The mitral valve regurgitation could not be reduced in 3 patients, and they went on to surgical repair, he said.
In the patients for whom the treatment works, mitral valve regurgitation has been reduced for as long as 6 months and New York Heart Association status has improved or remained unchanged for as long as 30 days.
“The clip is safe during the procedure,” he said, “and surgical options remain unchanged. It clearly warrants further study and ongoing trials.”
Enoxaparin Equal to Unfractionated Heparin in SYNERGY
Enoxaparin and unfractionated heparin were essentially equal when used in the rapid invasive treatment of patients with acute coronary syndrome, said investigators for the SYNERGY (Superior Yield of the New Strategy of Enoxaparin, Revascularization and Glycoprotein IIB/IIIA Inhibitors) in a presentation at a late-breaking clinical trials session of the ACC Scientific Sessions 2004.
The study enrolled more than 10 000 patients, of whom only 25% had received no prior antithrombotic medication. During the baseline hospitalization, 92% of the patients underwent angiography. In the enoxaparin group, 46% of patients underwent percutaneous intervention; in the unfractionated heparin group, it was 47%. Nineteen percent of enoxaparin patients underwent coronary artery bypass graft surgery, and 18% of the unfractionated heparin group underwent the surgery.
The percentage of death and myocardial infarctions was about 14% in both groups. The rate of death was about 3% in each group. The rate of myocardial infarctions was 11.7% in the enoxaparin group and 12.7% in the unfractionated heparin group.
There was significantly more bleeding in the enoxaparin group.
“Enoxaparin was statistically noninferior to unfractionated heparin,” said James Ferguson, MD, of the Texas Heart Institute in Houston.
A problem in the study was that 75% of patients in the study were already on antithrombotic therapy before they were entered into it, he said. “The purest group included the patients with no prior therapy.”
There is also the issue of crossover—patients who were put on non-study drug therapy after randomization—most often in the cath lab, he said. Looking at the numbers, he said, it indicates that such patients were more likely to bleed and may account for the excess bleeding in the enoxaparin group. However, he cautioned that post hoc analysis should not be used for clinical decision-making.
“Prior antithrombotic therapy is an issue we had not previous appreciated,” he said. “Also, postrandomization management appears to matter.”
How Low Should Blood Pressure Go?
Lowering the blood pressure of patients with coronary artery disease can prove detrimental, said a New Orleans–based researcher during a late-breaking session of the ACC Scientific Sessions 2004.
Franz Messerli, MD, of the Ochsner Clinic Foundation in Louisiana, was a leader in INVEST (International Verapamil SR-Trandolapril Study) which enrolled 22 576 high-risk patients with high blood pressure and coronary artery disease. Patients were randomized to receive verapamil SR or trandolapril and were monitored for an average of 2.6 years.
Patients with a diastolic blood pressure above 90 mm Hg or below 70 mm Hg had increased deaths from all causes as well as more nonfatal myocardial infarctions and strokes.
“Patients with occlusive coronary disease are put at risk of coronary events if diastolic pressure is too low,” said Dr Messerli.