Carvedilol Adds to ACE Inhibitor Benefits in Patients After Acute Myocardial Infarction
The β-blocker carvedilol appeared to improve and even reverse left ventricular remodeling that occurred in patients who had had an acute myocardial infarction and were treated with ACE inhibitors in a study appearing in this week’s issue of the journal Circulation (Circulation. 2004;109:201–206OpenUrl).
In this echocardiogram substudy of the massive CAPRICORN (CArvedilol Post infaRction survIval COntRol in left ventricular dysfunctioN) study, 127 patients were recruited to receive an echocardiogram after 1, 3, and 6 months of treatment with carvedilol or a placebo. Left ventricular volumes, ejection fractions, and wall motion score indexes were determined in a blinded fashion. After 6 months, patients who had received carvedilol had a left ventricular end-systolic volume that was 9.2 mL less than that of patients in the placebo group. The ejection fraction in the carvedilol group was 3.9% higher than that of the placebo group. The other measurements were not statistically different, according to the investigators, who were led by Robert N. Doughty, MD, of the University of Auckland, New Zealand.
The researchers wrote: “The results support the complementary effects of combination therapy with ACE inhibitors and carvedilol initiated early after acute MI [myocardial infarction] in patients with LV [left ventricular] dysfunction.”
Sirolimus-Eluting Stents Work in Real World, Too
The sirolimus- or rapamycin-eluting stent, when used outside the tightly confined environs of clinical trials, appears to be both safe and effective in reducing restenosis (and the repeat revascularization it requires) as well as major adverse cardiac events, said researchers from the Netherlands in a report in this week’s issue of the journal Circulation (Circulation. 2004;109:190–195OpenUrl).
One major concern about studies with the revolutionary sirolimus-eluting stents has been the tightly controlled patient populations in which the stents have been used. Many experts have questioned whether the stents will be as effective in the real world, where patients often have several health problems that might complicate the use of the drug-eluting devices.
In this registry, researchers from the Rotterdam Cardiology Hospital compared the results of the drug-eluting stents to those of bare-metal stents in unselected patients. The RESEARCH (Rapamycin-Eluting Stent Evaluated At Rotterdam Cardiology Hospital) Registry enrolled 508 patients who received only the sirolimus-eluting stents and compared their results to those of 450 patients who had received bare-metal stents in the period before the drug-eluting stents came into use.
In general, patients who received the drug-eluting stents had more complicated disease than those in the bare-metal stent group. After 1 year, patients who had died, suffered a heart attack, or needed revascularization in the lesion that was originally treated constituted 9.7% of the sirolimus group and 14.8% of the bare-metal stent group. After 12 months, the risk for needed revascularization in the target lesion was 3.7% for the sirolimus-eluting stent group and 10.9% for the bare-metal stent group.
The researchers argued for the authenticity of their results, noting, “The present study is a single-center experience from a tertiary referral center and lacks the obvious advantages of a multicenter, multinational randomized study. Furthermore, it is unlikely that a randomized study will be conducted in the context in which this study was performed, with virtually no exclusion criteria.”
Paclitaxel-Eluting Stent Effective as Well
Nine months after it was deployed, the slow-release, polymer-based, paclitaxel-eluting stent appeared to be safe and reduced the rate of restenosis in 662 patients who received it when compared with 652 patients who received bare-metal stents, said researchers in a report in the January 15, 2004, issue of The New England Journal of Medicine (N Engl J Med. 2004;350:221–231OpenUrlCrossRefPubMed).
The study, carried out at 73 US centers, enrolled patients who were slated to receive a stent to treat a single, primary stenosis of a coronary artery. In patients who received the bare-metal stent, 11.3% required revascularization in the target lesion by 9 months. In comparison, only 3% of patients who received the paclitaxel-eluting stent required such revascularization. Rates of death from cardiac causes or heart attack were similar in both groups, as was occurrence of thrombosis in the stent.
The researchers wrote, “Appropriately powered, head-to-head randomized trials comparing different drug-eluting stent systems are required to evaluate their relative safety and efficacy.” To date, paclitaxel and rapamycin are the most commonly evaluated compounds in drug-eluting stents.
Abciximab Not Needed?
The glycoprotein IIb/IIIa inhibitor abciximab appeared to offer no additional benefit in low- to intermediate-risk patients who underwent percutaneous coronary intervention after receiving a high loading dose of clopidogrel, said European researchers in the January 15, 2004, issue of The New England Journal of Medicine (N Engl J Med. 2004;350:232–238OpenUrlCrossRefPubMed.) The trial was led by Adnan Kastrati, MD, of Deutsches Herzzentrum, Munich, Germany.
In this prospective, randomized, double-blind trial, 2159 patients with coronary artery disease undergoing percutaneous intervention were enrolled in the study. Of these, 1079 received abciximab and 1080 placebo. All patients received 600 mg of clopidogrel at least 2 hours before undergoing the intervention.
There appeared to be no difference between the groups when the primary end points of death, myocardial infarction, and urgent target-vessel revascularization were compared 30 days after the randomization. Four percent of patients in the abciximab group and 4 percent in the placebo group reached one of the primary end points. However, the researchers noted, “The lack of benefit of abciximab after a high loading dose of clopidogrel should not be applied to patients at higher risk than those enrolled in this trial.”
CABG and Hospital Volume
In a study that goes against conventional wisdom, researchers from the Duke Clinical Research Institute in Durham, NC, found that the volume of coronary artery bypass graft (CABG) procedures performed at an institution may not be an adequate indicator of quality. In a report in the January 14, 2004, issue of The Journal of the American Medical Association (JAMA. 2004;291:195–201), Eric D. Peterson, MD, MPH, of the Duke Clinical Research Institute, and his colleagues examined the association between the number of CABG procedures in institutions and their outcomes, using data from the Society of Thoracic Surgeons’ National Cardiac Database. The analysis included 267 089 procedures performed at 439 US hospitals between January 1, 2000, and December 31, 2001.
Overall, the mortality rate attributed to the surgery was 2.66%. Eighty-two percent of the hospitals performed fewer than 500 procedures per year. Adjusting for patient risk and clustering, operative mortality rates dropped 0.07% for every 100 additional CABG procedures performed at an institution. However, said Dr Peterson, the association was not observed in patients under the age of 65 years or in those who had a lower risk going into the operation. The results were also clouded by the numbers of procedures performed annually by surgeons.
The authors wrote, “Hospital volume had generally poor predictive accuracy as a means of identifying hospitals with significantly better or worse CABG mortality rates. In this national study we found that hospital procedural volume was only modestly associated with risk-adjusted CABG mortality rates; however, there were many low-volume hospitals with low mortality rates and some high-volume centers with rates higher than expected. This study suggests that hospital CABG surgery volume is best considered as a surrogate for quality in a setting where other more direct process and outcome assessments are not available.”
Ephedra Danger Confirmed
Long QTc interval and higher systolic blood pressure occurred in individuals who received a dietary supplement containing ephedra and caffeine in a study that appeared in the January 14, 2004, issue of The Journal of the American Medical Association (JAMA. 2004;291:216–221OpenUrlCrossRefPubMed). The information appeared after the US Food and Drug Administration announced that it planned to ban the use of ephedra in such supplements because of reported adverse events.
In the JAMA study, Brian F. McBride, PharmD, from the University of Connecticut School of Pharmacy, and his colleague evaluated the effect of Metabolife 356 in 15 health volunteers whose ages averaged about 27 years. Individuals were randomized to receive either the dietary supplement or a placebo as their first treatment. A week later, the volunteers received the other treatment. Their heart rates and blood pressures were monitored before taking the supplement or placebo and 1, 3, and 5 hours afterwards. Those who received the supplement with ephedra and caffeine had a longer QTc interval (419.4 versus 396.1 ms in the placebo group) and a higher systolic blood pressure (123.5 versus 118.93 mm Hg in the placebo group).
The authors noted that more than half of the subjects had QTc interval increases of at least 30 seconds while taking the supplement, an increase that is recognized by the European Center for Proprietary Medicinal Products as having the potential for causing torsade de pointes, a potentially fatal complication. The authors wrote, “The ephedra- and caffeine-containing dietary supplement Metabolife 356 increased the mean maximal QTc interval and systolic blood pressure. Since the actual ingredient or ingredients in Metabolife 356 responsible for these findings are not known, patients should be instructed to avoid this and similar dietary supplements until more information is known about their safety.”