From This Week’s Issue of Circulation: Stenosis and the Drug-Eluting Stent
Stenosis, identified through coronary angiography, occurs rarely after implantation of a sirolimus-eluting stent. However, when it does, it most often occurs because of factors relating to the lesion itself or in patients with diabetes, said researcher from The Netherlands in a report in this week’s issue of the journal Circulation (Circulation. 2004;109:1366–1370OpenUrl).
Researchers participating in the RESEARCH (Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital) study evaluated a cohort of patients with complex disease who had been treated with sirolimus-eluting stent(s). A total of 238 patients with 441 lesions were identified and underwent angiographic follow-up 6 months after receiving their stents.
The researchers wrote, “Angiographic restenosis after SES [sirolimus-eluting stent] implantation in complex patients is an infrequent event (7.9% of lesions), occurring mainly in association with local, lesion-based characteristics and diabetes mellitus.”
From the American College of Cardiology’s Scientific Sessions 2004
The Value of ACE Inhibitors in Diabetics PERSUADEd
NEW ORLEANS, La—Diabetics with stable coronary artery disease benefited as much from treatment with the ACE inhibitor perindopril as did their nondiabetic counterparts, said Kim Fox, MD, of The Brompton Hospital in London, during a late-breaking trials session of the American College of Cardiology Scientific Sessions 2004 meeting here March 6–10, 2004.
The diabetics were part of a study called PERSUADE (PERindopril SUbstudy in coronary Artery disease and DiabEtics), a substudy of EUROPA (European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease). The 1502 diabetic patients with stable coronary artery disease were randomly selected to receive 8 mg of perindopril daily or placebo. They were all receiving standard therapy that included aspirin, statins, and β-blockers, when appropriate.
Patients were monitored for approximately 4 years or until they reached one of the primary end points: cardiovascular death, myocardial infarction, or cardiac arrest. All patients underwent a 4-week run-in period with perindopril, during which the drug was titrated from 4 to 8 mg.
“The outcome was as we had expected,” said Dr Fox. “It was far worse than it was in those patients without diabetes. However, there were similar percentage reductions of the primary and secondary end points in favor of the ACE inhibitor perindopril.” The reduction for the combined primary end point of cardiac death, myocardial infarction, or cardiac arrest was 19%, very similar to the 20% reduction seen in EUROPA. The relative risk reduction was 23%, compared with 24% in EUROPA.
“It is quite clear that diabetics are at substantial cardiovascular risk,” said Dr Fox. “Perindopril 8 mg once daily reduces cardiovascular events in patients with coronary artery disease and diabetes. These were patients without apparent heart failure on optimal therapy. That means you can prevent one cardiovascular death or nonfatal myocardial infarction by treating 27 patients over 4 years.”
Ezetimibe Adds to Power of Statins
Adding ezetimibe, a drug that inhibits absorption of cholesterol in the gut, to a statin, which inhibits the liver’s cholesterol production, reduced low-density lipoprotein cholesterol (LDL-C) in the bloodstream by 23% in the EASE (Ezetimibe Add-On to Statin Effectiveness) trial, said Thomas Pearson, MD, of the University of Rochester (NY) School of Medicine and Dentistry, during the American College of Cardiology Scientific Sessions 2004.
“Ezetimibe is from a new class of cholesterol-lowering agents that inhibit cholesterol absorption in the intestine,” said Dr Pearson. “When it is added to the statin, it blocks cholesterol at two points.”
In the EASE trial, 3030 patients with hypercholesterolemia drawn from 299 private practices around the United States were enrolled. “Particular emphasis was put on the practices that saw African-Americans and Hispanics. Two thirds of the patients were randomized to the statin and 10 mg ezetimibe. The others were in the statin-plus-placebo group.”
In the study, 70% of the patients on ezetimibe got to the LDL-C goals suggested in federal guidelines. Overall, the combination of ezetimibe plus statin reduced cholesterol 23%, compared with 3% in the statin-alone group.
“It works with all the currently used statins,” said Dr Pearson. “Ezetimibe may be better than doubling the statin, which results in only a 6% to 8% reduction in the levels of LDL-C. The tolerability was excellent.”
Moderate Lipid Lowering Equals Intensive Treatment in Preventing Ischemia
Moderate lipid lowering was as effective as intensive treatment in reducing ischemic attacks, said Peter Stone, MD, of The Brigham and Women’s Hospital in Boston, Mass, during the American College of Cardiology’s Scientific Sessions 2004.
“The hypothesis was that ischemia during activities could be improved by intensive or moderate lowering of LDL-C,” he said.
In the study, approximately 300 patients were randomized to 3 treatment groups. One group received atorvastatin in dosages that allowed reduction of LDL-C to 80 mg/dL or 80 mg of drug. A second received the same dosages of atorvastatin along with vitamins C and E. The third group was put on a lipid-lowering diet combined with lovastatin to achieve an LDL-C of 130 mg/dL or less.
At 6 months, LDL in the atorvastatin groups was 85 mg/dL. In the control group, it was 121 mg/dL. Those levels were maintained for a year, said Dr Stone.
At the beginning of the study, each patient had between 4.5 and 5 ischemic events every 2 days. These decreased to 2.5 to 3 every 48 hours in each of the 3 groups. The periods of ischemia lasted, on average, 90 minutes at the beginning of the study but were only 55 to 60 minutes at the end of the study in each of the groups. There was no change in heart rate activity.
When the study started, patients could exercise 5 to 6 minutes before the onset of an ischemic events. That period increased about 1 minute in each of the 3 groups at 6 and 12 months.
“The benefits of cholesterol-lowering were similar,” said Stone. “It did not depend on the statin use, on the antioxidant vitamins, or diet.” Moderate reduction of LDL-C is sufficient to reduce ischemia, he said. Lowering the levels further would not appear to have an effect on this end point, he said.
“For a harder end point like preventing progression of atherosclerosis, lower cholesterol is obviously better,” he said.
Imaging Technique INSPIREs Heart Attack Treatment
Patients who have had an acute myocardial infarction and who were found to be at low risk by a stress myocardial perfusion scintigraphy test do not need coronary angiography, said John Mahmarian, MD, Professor of Medicine at Baylor College of Medicine, during a late-breaking clinical trials session of the American College of Cardiology Scientific Sessions 2004.
“Up until now, there have been no trials using state of the art myocardial imaging studies in these patients,” he said. “We used adenosine as a pharmacologic stress tester.” That allowed use of the testing technique within days of the attack. The INSPIRE (AdenosINe Tc99m Sestamibi spect Post-InfaRction Evaluation) trial enrolled 728 patients at multiple centers around the nation.
The test allowed physicians to determine the size of the perfusion abnormality left after the heart attack in each patient. Patients with small defects were considered at low risk; those with intermediate-sized defects were at intermediate risk, etc.
Patients classified as low risk by the scan had a less than 3% rate of death and myocardial infarction at 1 year and a death rate of less than 1% after the initial imaging study. Eighty percent of patients in the high-risk group who received either revascularization or intensive medical therapy had at least a 9% decrease in ischemic perfusion defect size in the year.
“It was highly unlikely that someone characterized low risk by nuclear imaging would benefit from coronary artery bypass grafting or percutaneous intervention,” said Dr Mahmarian. “The high-risk population (by scan) could be targeted for more intensive anti-ischemic procedures.”
“It appears that not only can nuclear imaging assess risk effectively, it can also track perfusion over time in both patients at high and low risk,” he said. “Perfusion imaging can accurately assess risk in patients who don’t need invasive techniques and in those who are at high risk and who would benefit from anti-ischemic therapies. It improves risk stratification. By using sequential perfusion imaging, one can monitor the effects of different therapies on myocardial perfusion. This means better triage from the beginning.”