QTc Interval and B-Type Natriuretic Peptide Levels Predict Death in Patients With Advanced Heart Failure
A prolonged QTc interval in the presence of high B-type natriuretic peptide levels strongly predicts a negative outcome for patients with heart failure, according to the researchers led by Bojan Vrtovec, MD, PhD, of the Cardiopulmonary Transplantation Service at Texas Heart Institute at St Luke’s Episcopal Hospital in Houston, Tex. The report of their research appears in this week’s issue of Circulation (Circulation. 2003;107:1764–1769).
In this study, researchers measured QTc levels in 241 heart failure patients who arrived at the hospital with B-natriuretic peptide levels that were greater than 400 pg/mL. The QTc interval was prolonged in 122 patients and normal in 119. The B-natriuretic peptide levels were not significantly different between the members of the groups. During follow-up, 46 patients died, 9 underwent transplantation, and 17 received implantation of a left ventricular assist device. Deaths were attributed to pump failure in 24 patients, sudden cardiac death in 18, and non–heart-related causes in 4.
The researchers reported that Kaplan-Meier survival curves were 3 times higher in patients with normal QTc intervals than in those with prolonged intervals. The researchers wrote: “It may be of particular significance in identifying those at risk who are already known to have pressure or volume overload of the left ventricle. Further studies are needed to determine its pathophysiological significance and whether it can be used with other markers to develop a multivariate risk stratification protocol that could aid in determining the need for advanced therapies.
Statins Before Percutaneous Coronary Intervention in Patients With High Levels of Inflammation
Statin therapy given before percutaneous coronary intervention was associated with a reduction in death rate among patients with high levels of C-reactive protein in a prospective study of patients who underwent such procedures at the Cleveland Clinic in the year 2000, according to researchers led by Albert W. Chan, MD, MSc, Associate Director of the Catheterization Laboratory at the Ochsner Clinic Foundation in New Orleans, La. Their findings are reported in the journal Circulation (Circulation. 2003;107:1750–1756).
According to the researchers, the 39.6% of the patients who received statins before the procedure had lower C-reactive protein levels and fewer periprocedural myocardial infarctions. At 1 year, statin therapy was positively associated with survival.
However, the researchers noted, the prognostic value of C-reactive protein levels was relevant only in patients who did not receive statin therapy.
Late-Breaking Trials From the 52nd Scientific Sessions of the American College of Cardiology (Chicago, Ill; March 30– April 2, 2003)
Stents First Revascularization Choice
CHICAGO—Stents remain the first choice in revascularization, even compared to off-pump, coronary artery bypass grafting, said Peter de Jagere, MD, of Utrecht, the Netherlands, during the first presentation of data from the OctoStent arm of the Octopus study at the first session of late-breaking clinical trials at the 52nd Scientific Sessions of the American College of Cardiology meeting here March 30 through April 2, 2003.
In the study, 138 patients were assigned to stenting and 142 to coronary artery bypass grafting, said Dr de Jagere. Although most of the patients had single-vessel disease, a small percentage in each arm of the study had double- and even triple-vessel disease, he said.
Results from the two arms of the study were similar. Mortality rates were 0.9% in the stent group and 1.4% in the surgery group; cardiac death rates were 0.9% in the stent group and 2.8% in the surgery group; and acute myocardial infarction rates were 4.4% in the stent group and 4.9% in the surgery group.
At 1 year, 96% of patients who received a stent had survived free of stroke or acute myocardial infarction. Rates of stroke- and acute myocardial infarction–free survival with no need for revascularization were 91.5% for the off-pump surgery group and 85.5% for the stent group. Safety data were the same, said de Jagere. Length of stay, as would be expected, was longer for the surgery group—5.7 days versus 1.4 days for the stent group.
The major difference was in cost, he said. The cost in US dollars for hospitalization was $5013 for those in the stent group versus $7508 for those in the off-pump surgery group. Follow-up costs were $2020 for the stent group versus $2010 for those who received off-pump surgery. The difference in that statistic was attributable to the more frequent need for revascularization in the stent group.
However, he said, stent implantation dominated off-pump surgery in a common economic measurement called quality–of–life-year analysis, even though there was difference in the composite medical end points of death, stroke, acute myocardial infarction, or need for target vessel revascularization between the two.
“Off-pump surgery was associated with less repeat revascularization,” said de Jagere. “What is known is that [with] percutaneous coronary intervention, you can do a minimally invasive approach in an outpatient setting. The drawback is that you have to tell patients that there is a good chance that they will need a repeat in the year.”
However, he noted that there was no difference in quality-of-life measurements, and those who received the stent recovered more quickly. In addition, he said, “Stent implantation was significantly less costly.”
“Stent implantation can be recommended as a first choice in revascularization,” he said.
A Bull’s-Eye for the ARCHeR Trial
CHICAGO—Early results from the ARCHeR (ACCULINK for Revascularization of Carotids in High-Risk Patients) trial show that carotid stenting using a filter can be performed safely in high-risk patients, and that results compare favorably with those of historical controls who received traditional carotid endarterectomy, said Mark H. Wholey, MD, chairman of the Pittsburgh Vascular Institute in Pittsburgh, Pa, at the first session of late-breaking clinical trials at the 52nd Scientific Sessions of the American College of Cardiology meeting here March 30 through April 2, 2003.
In this multicenter trial, Dr Wholey and his colleagues reported that before the procedure, the 437 patients registered with the study received aspirin, clopidogrel, and heparin. After the procedure, they again received aspirin and clopidogrel daily for 2 to 4 weeks.
The mean age of the patients was 70 years, and nearly two thirds were male. Most suffered from hyperlipidemia and hypertension. Approximately 32.2% had suffered a restenosis of the carotid artery after a previous carotid endarterectomy. Their ejection fraction, on average, was less than 30%, and most had 2 or more diseased coronary arteries.
The stent was deployed successfully in 92.7% of patients with visible debris found in the filter baskets.
At 30 days after the procedure, the rate of myocardial infarctions was 2.1%. The rate of stroke and death was 6.6%, and the rate of stroke, death, or myocardial infarction was 7.8%. In those with restenosis, the rate of stroke, acute myocardial infarction, and/or death was 6.4%. In patients with renal failure dependent on dialysis, the rate of stroke, myocardial infarction, and/or death was 28.6%, an important consideration, according to Dr Wholey.
Sirolimus-Eluting Stents Appear Cost-Effective
CHICAGO—Even though he expects sirolimus-eluting stents to be triple the cost of their bare-metal brothers, David J. Cohen, MD, MSc, of Beth Israel Deaconess Hospital in Boston, Mass, anticipates that the drug-eluting stents will be more cost effective because they reduce the need for additional revascularization in the target lesion.
In his cost analysis of the use of sirolimus-eluting stents presented at the second session of late-breaking clinical trials at the 52nd Scientific Sessions of the American College of Cardiology meeting here March 30 through April 2, 2003, Dr Cohen and his colleagues analyzed data from the SIRIUS (Sirolimus-Eluting Stent in Coronary Lesions) trial, in which more than 1000 patients with coronary disease were randomized to receive the drug-eluting stent or a bare-metal stent.
Because he expects the drug-eluting stent (for which a price has yet to be set) to cost $2000 more than stents being used today, he estimated the cost of the procedure to be $7252 versus $4395 for those who received the bare-metal stent. The hospital costs for those who receive the drug-eluting stents were estimated at $11 345 versus $8464 for those who received the common stent.
Costs from discharge to 12 months were $5468 for the drug-eluting stent group and $8040 for the control group. The 12-month total was $16 813 for the drug-eluting stent group versus $16 504 for the control group, resulting in $309 excess cost in the drug-eluting stent group. The difference in cost between the two groups was not statistically significant, meaning that the two numbers were essentially the same.
“While the difference of $309 was not statistically significant, even a difference of $309 could be a significant amount, considering the numbers of patients who undergo percutaneous coronary intervention in the United States,” said Dr Cohen.
If longer stents were available, the difference in the 1-year cost would be even closer—$136. If longer stents were available and clopidogrel became the standard of care for all stent implantations (eliminating that difference in costs between the two groups), the difference becomes $96 in favor of the drug-eluting stent, said Dr Cohen. That would make the sirolimus-eluting stent the dominant form of care because it would improve both outcomes and costs in the long term.
The sirolimus-eluting stent could be said to be effective only for single-stent lesions from this analysis. Speculating on the cost-effectiveness of the drug-eluting stent in patients with multivessel disease, Dr Cohen noted that it would depend on the treatment with which the stent was being compared.
“If we compare it to patients currently treated with bypass, even if we used 3 to 4 stents, it would result in lower costs and better outcomes,” he said. “The clinical issue is paramount here.”
TAXUS II: After One Year
CHICAGO—Paclitaxel-coated stents appear to prevent rather than delay in-stent restenosis, said Antonio Colombo, MD, of Columbus Hospital in Milan, Italy, during his presentation of 12-month data from the TAXUS II trial (named for the drug-eluting stent involved in the study). He spoke during a late-breaking clinical trial meeting at the 52nd Scientific Sessions of the American College of Cardiology meeting here March 30 through April 2, 2003.
The study evaluated the efficacy of the paclitaxel-coated stent in a slow- and moderate-release formulation versus treatment with a bare-metal stent. The amount of paclitaxel on the slow-release and moderate-release stents is the same, said Dr Colombo.
This study evaluates the effect of the stent 6 months after patients finished their half-year stint of taking clopidogrel.
There were 131 subjects in the slow-release group and 134 in the moderate-release group. There were 270 patients in the combined control groups. The primary end point was determined by ultrasound.
Dr Colombo reported no stent thrombosis in the control group, 1 in the slow-release group, and 1 in the moderate-release group. After 12 months, major adverse coronary events such as death, myocardial infarction, overall target vessel revascularization, target lesion revascularization, and coronary artery bypass grafting was 21.7% for the control group, 10.9% for the slow-release group, and 9.9% for the moderate-release group. There were 2 deaths in the control group and none in the group of patients receiving the paclitaxel stents.
“The bare-metal stent group continues to have excellent 12-month MACE [meaning a low level of major adverse cardiac events] and target lesion revascularization outcomes,” said Dr Colombo. “The beneficial effect of the TAXUS stent on MACE, restenosis, and target lesion revascularization after termination of clopidogrel is sustained over time. The MACE-free survival from 6 months to 12 months suggests that TAXUS prevents rather than delays restenosis.”
Abciximab Makes “No Difference”
CHICAGO—Abciximab made “no difference” in patients who underwent coronary stenting after pretreatment with a high loading dose of clopidogrel, said Adnan Kastrati, MD, of the Deutsches Herzzentrum in Munich, Germany, in describing the ISAR REACT trial (Intracoronary Stenting And Anti-Thrombotic Regimen And Rapid Early Action For Coronary Treatment) at a late-breaking clinical trial session at the 52nd Scientific Sessions of the American College of Cardiology meeting here March 30 through April 2, 2003.
This multicenter, double-blind, placebo-controlled trial had participating centers in Germany, the Netherlands, and the United States, said Dr Kastrati.
In order to speed up the effect of clopidogrel, the trial planners decided to give a higher loading dose of the drug (600 mg) in order to achieve a maximum effect within 2 to 4 hours. The potent antiplatelet drug abciximab was added to the treatment with clopidogrel to determine if it would increase protection against adverse events.
All patients received the maximal dose of clopidogrel within 2 to 4 hours of the procedure. They received aspirin, and abciximab in a bolus. The placebo group received an extra amount of heparin and a placebo infusion for 12 hours. Oral clopidogrel was given after the procedure twice a day and then once a day orally after discharge.
The primary end point in the study of 1079 patients who received abciximab and 1080 who received placebo was a composite of death, major myocardial infarction, or urgent target vessel revascularization in the first 30 days after the procedure.
All patients received percutaneous coronary intervention and were followed up for 30 days. The primary end points affected 4.2% of patients in the abciximab group and 4% of patients in the placebo group, said Dr Kastrati. There was no difference in any of the various end points, he said.
“In patients like these who undergo elective percutaneous coronary intervention with a high loading dose of clopidogrel, allowing enough time for maximal inhibition of aggregation to be achieved, abciximab was associated with no clinical value in the first 30 days,” said Dr Kastrati. He pointed out that his patient population represented a low-risk cohort, which might have affected the outcome.
EPHESUS Proves Value of Aldosterone Blockade
CHICAGO—One life will be saved for every 50 patients with severe left ventricular dysfunction after acute myocardial infarction who are treated with the aldosterone blocker eplerenone in addition to maximal medical therapy, said Bertram Pitt, MD, of the University of Michigan at Ann Arbor School of Medicine, while describing the EPHESUS (Eplerenone Post-AMI Heart failure Efficacy and Survival Study) trial during the 52nd Scientific Sessions of the American College of Cardiology, March 30 through April 2, 2003.
The findings “have important implications not only for patients with acute myocardial infarction and heart failure but also for a variety of cardiovascular diseases currently treated with an ACE inhibitor and β-blockers,” said Dr Pitt.
A total of 3319 patients were randomized to 25 mg of eplerenone per day (initially titrated to a maximum dose of 50 mg) and 3302 to placebo. Those in the treatment group received a mean dose of 43 mg of eplerenone in addition to optimal medical therapy. Primary end points of the study were death from any cause and death from cardiovascular causes or hospitalization for acute myocardial infarction, stroke, or ventricular arrhythmia.
During a follow-up period of 1 year and 4 months, 478 subjects in the treated group and 554 in the placebo group died. Of these deaths, 407 in the treated group and 483 in the placebo group were from cardiovascular causes, said Dr Pitt. Deaths from cardiovascular causes or hospitalization for a variety of cardiovascular events were reduced by eplerenone.
In addition, he said, the rate of sudden death was reduced in the treatment group by 21%, he said. Patients who received eplerenone had a significantly lower rise in blood pressure during follow-up. There was a small but significant rise in potassium and creatinine over the year, he said.
There was a significant 15% reduction in all-cause mortality in the group that received the aldosterone blocker and a 17% reduction in cardiovascular mortality. Patients on recommended therapy had a 27% reduction in all-cause mortality, and those on maximal therapy including ACE inhibitors, β-blockers, aspirin, stains, and appropriate reperfusion therapy had a 26% reduction in all-cause mortality.
Total mortality and total hospitalization were reduced by 8% in the treatment group, he said. Treatment with eplerenone was associated with fewer side effects than those seen with spirolactone, said Dr Pitt. There was no evidence of increased menstrual disorders, gynecomastia, or impotence, he said. There was a 1.6% increase in serious hyperkalemia as well as a 4.7% absolute decrease in hypokalemia.
Dr Pitt said the fact that greater effects were seen in patients who received the most treatment demonstrated that “on top of what we have today, we can do better.” The report of the study was released online at http://content.nejm.org/ after the presentation on March 31, 2003 (N Engl J Med. 2003;348:1309–1321).
Benefits of Cardiac Resynchronization Therapy and Cardiac Resynchronization Plus an Implantable Defibrillator in Chronic Heart Failure
The use of cardiac resynchronization therapy with an implantable defibrillator resulted in a 43% reduction in mortality in the first year, said Michael Bristow, MD, PhD, of the University of Colorado Health Sciences Center in describing the COMPANION (Comparison of Medical Therapy, Pacing, and Defibrillation in Chronic Heart Failure) trial along with Arthur M. Feldman, MD, PhD, of Thomas Jefferson Medical College in Philadelphia. They presented their data at a late-breaking clinical trial session at the 52nd Scientific Sessions of the American College of Cardiology meeting here March 30 through April 2, 2003.
A total of 1634 patients at 128 centers in the United States were enrolled in the trial. They were randomized to 1 of 3 arms: optimal pharmacological therapy alone, optional pharmacological therapy plus biventricular cardiac resynchronization therapy, or optional pharmacological therapy with biventricular cardiac resynchronization therapy plus implantable cardiac defibrillator at a ratio of 1 to 2 to 2.
While emphasizing that the data are still preliminary and require additional evaluation, Dr Bristow said he feels that the study proves the value of the therapies. Cardiac resynchronization therapy and cardiac resynchronization therapy plus implanted defibrillator each resulted in a 19% reduction in the primary end point of all-cause mortality and all-cause hospitalization.
“The reduction in the combined end point of all-cause death and hospitalization appears due to cardiac resynchronization therapy since the reductions were the same” with or without implanted defibrillator, said Dr Bristow.
While cardiac resynchronization therapy was associated with a reduction in mortality, it was not statistically significant. However the addition of the defibrillator to the resynchronization therapy reduced mortality by 43% over a year, a figure that was statistically significant, he said.
If this preliminary analysis of the data proves valid, Dr Bristow said cardiac resynchronization therapy and cardiac resynchronization therapy with implantable cardiac defibrillator reduced heart failure hospitalization by more than 30%, meaning that it would be cost-effective in treatment of heart failure. He pointed out that cardiac resynchronization therapy with implantable cardiac defibrillator can lower mortality substantially, even in a population that receives the best of medical management.
In the long run, he said, the decision as to which to use boils down to the analysis of the individual patient. “While cardiac resynchronization therapy alone reduces hospitalization and improves quality of life, cardiac resynchronization therapy with implantable cardiac defibrillator has a greater effect on mortality. Not all patients want to liver longer. Some just want to live better.”
Polish Skeletal Myoblast Treatment for Heart Failure
CHICAGO—Most of the patients who received transplants of skeletal myoblasts into their myocardium during coronary artery bypass have maintained at 1 year the increase in ejection fraction seen at 4 months after the transplantation, said Tomasz Siminiak, MD, of the University School of Medical Sciences in Poznan, Poland, at a late-breaking clinical trial session at the 52nd Scientific Sessions of the American College of Cardiology meeting here March 30 through April 2, 2003.
Dr Siminiak, who presented the data of his experiment at the September European Society of Cardiology meetings in Berlin, noted that one of the 10 patients died 7 days postoperatively, probably in association with myocardial infarction identified at autopsy.
The cells were taken in a biopsy from the vastus lateralis and expanded to 20 million cells in culture. The myoblasts were introduced into the postinfarction scar tissue during coronary artery bypass grafting.
One concern was that ventricular tachycardia seen in the early postoperative period may have resulted from differing rhythms in the heart cells and the skeletal myoblasts. The problem was managed with short-term amiodarone, he said. Another current theory about the cause of the ventricular tachycardia is that an immunologic reaction occurs when some of the transplanted cells die.
“Restoring this missing myocardium is an attractive option that we can continue to pursue,” said Dr Siminiak.
Aggrastat to Zocor—or at Least A
CHICAGO—The “A” phase of the Aggrastat to Zocor trial proved the “noninferiority” of enoxaparin (Lovenox) compared to unfractionated heparin in combination with tirofiban and aspirin in the treatment of patients with non–ST-segment-elevation acute coronary syndrome, said Michael Blazing, MD, Associate Professor at Duke University Heart Failure Center.
“This trial met its primary end point,” said Dr Blazing as he presented his results in a late-breaking trial session of the 52nd Scientific Sessions of the American College of Cardiology here. “Enoxaparin is not inferior to unfractionated heparin (in this group) for death, myocardial infraction, and refractory ischemia. Based on this and other studies, enoxaparin is an attractive alternative to heparin when either is used with tirofiban and aspirin. It is simple to use, has favorable efficacy trends, a low rate of bleeding and transfusion.”
A total of 3987 patients with non–ST-segment-elevation acute coronary syndrome were enrolled in the study. All patients received tirofiban and aspirin. A total of 2026 were assigned to the enoxaparin group and 1961 to the unfractionated heparin group.
The primary end points were death, myocardial infarction, or refractory ischemia at 7 days, said Dr Blazing. At 7 days, there had been 184 events in the unfractionated heparin group and 169 in the enoxaparin group, he said.
That was not enough to demonstrate superiority of enoxaparin as a treatment, but it did show “noninferiority,” he said. Bleeding and transfusion rates were low in the both groups, and the differences were not statistically significant.
“The trial met its primary end point,” said Dr Blazing. “Enoxaparin was not inferior to unfractionated heparin in treatment for death, MI [myocardial infarction], and refractory ischemia.”
The study did not address patients who receive early invasive therapy, and that was not the point, he said.
The “Z” or second phase of the study compares early aggressive treatment with statins to later treatment.
The Value of the Placebo
CHICAGO—Regional therapy with vascular endothelial growth factor proved no better than placebo in the treatment of peripheral artery disease, said Sanjay Rajagopalan, MD, an Associate Professor of Internal Medicine at the University of Michigan at Ann Arbor, during a late-breaking clinical trials session at the 52nd Scientific Sessions at the American College of Cardiology.
All patients had serious intermittent claudication only in one leg, he said. The study sought to determine whether the gene therapy could improve peak walking time on a treadmill within 12 weeks of therapy. He also sought to determine if the treatment was safe.
A total of 105 patients were randomized to receive placebo, low-dose VEGF122, or high-dose VEGF122. The gene was attached to an inactivated adenovirus and the gene-virus combination was given to the patients by intramuscular injection.
“There was no improvement in the primary end point [of increased walking time on the treadmill] in the treatment groups versus placebo. They all improved,” said Dr Rajagopalan. There was no difference in the ankle-brachial index, a walking impairment questionnaire, or other physical measurements.
“There was no improvement in physical component scores in all 3 groups up to 26 weeks,” he said. “This was the largest placebo-controlled adenovirus gene transfer trial in cardiovascular disease to date. There was a larger than expected placebo response, but there was no evidence of efficacy over placebo in the 26 weeks.”
Asked if he could understand the findings, Dr Rajagopalan said, “That is the $100 000 question. There are several aspects to be examined,” including the adenoviral vector, the transgene that was chosen.
“Peripheral artery disease might take more to be able to detect changes,” he said. He said there is also some evidence that treating skeletal muscle might be different from treating myocardium.
“Overexpression of VEGF [vascular endothelial growth factor] alone might be insufficient,” he said.
Smoke-Free Ordinance Lowers Heart Attacks
In the 6 months that Helena, Montana’s smoke-free ordinance was in effect, there was a 60% reduction in the incidence of acute myocardial infarction, said Richard Sargent, MD, who practices in the small western town.
The decrease was compared to incidence of acute myocardial infarction in the previous 4 years. While the decrease amounted to only 4 fewer myocardial infarctions than seen in the previous years, it demonstrates that “smoke-free ordinances have an immediate and plausible effect on AMIs [acute myocardial infarctions],” said Dr Sargent. The result, which was statistically significant, was also biologically plausible on the basis of studies of the effect of second-hand smoke on platelet aggregation, arrhythmias, and vasospasm.
In contrast, he said, there was no change in the incidence of acute myocardial infarction in the area immediately outside of Helena.
In terms of policy change, he said, “You must educate and then legislate. What we need to do first is to get the data published, publicized, and be certain that people understand that not only does second-hand smoke cause cancer, it also has an immediate effect on heart disease.”
Long Lesion, Small Lumen? No Problem in C-Sirius
CHICAGO—Patients with long lesions in small vessels can benefit from a sirolimus-eluting stent, said Eric Schampaert, MD, of the Hôpital Sacre Coeur in Montreal, Quebec, Canada, during the final late-breaking clinical trials session at the 52nd Scientific Sessions of the American College of Cardiology.
The C-SIRIUS (SIRolImUS-Eluting Stent in De Novo Native Coronary Lesions) enrolled 100 patients with single new lesions and randomized them to receive either sirolimus-eluting stent or a bare-metal stent. Patients were followed up angiographically and clinically for at least 8 months, said Dr Schampaert. The average minimal lumen diameter in the control group was 2.62 mm, and it was 2.65 in the sirolimus group. The average lengths were 12.6 mm in the control group and 14.5 mm in the sirolimus group.
All results in the trial were statistically significant in favor of the sirolimus stent, he said. The average minimal lumen diameter in the control group was 1.5 mm and in the sirolimus group 2.45 mm.
Nine patients in the control group and 2 in the sirolimus reached the clinical end points of death, myocardial infarction, emergency coronary artery bypass grafting, or percutaneous coronary intervention. There were no deaths in either group and no Q-wave myocardial infarctions, said Dr Schampaert.
“Findings from previous studies can now be extended to patients with long, smaller lesions,” said Dr Schampaert.
ASCOT Ties It Up
CHICAGO—Lowering lipids in patients with high normal or slightly elevated cholesterol levels resulted in a 36% reduction in the risk of fatal and nonfatal coronary heart disease, said Björn Dahlof, MD, of Sahlgrenska University in Gothenburg, Sweden, in explaining the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) that was terminated early at 3.5 years. He spoke during the last session of late-breaking clinical trials at the 52nd Sessions of the American College of Cardiology.
In addition, he said, there was a 27% reduction in the risk of stroke and a 27% reduction in cardiovascular events and procedures. The difference in total mortality was not statistically significant. There were 111 deaths in the treatment group and 130 in the placebo.
“Risk reductions were unrelated to baseline cholesterol levels,” he said. The average cholesterol level in the patients in the trial was 250 mg/dL, slightly above the maximum level considered normal in US guidelines.
Patients who enrolled in the study were randomized to atorvastatin (Lipitor) (n=5168) and placebo (n=5137). It is part of a larger study that is enrolling 18 000 patients to test strategies for treating hypertension.
However, in September 2002, the data safety monitoring board of the trial found that there was a highly significant lower risk of stroke and coronary disease in one arm of the study and recommended that the study be terminated early.
Blood pressure was substantially reduced in all patients in the lipid-lowering part of the trial, said Dr Dahlof. “The average blood pressure was 138/80 mm Hg.”
He said it is important to note that the benefits of the statins were seen against a background of good blood pressure control. They were also seen in the absence of increased risk, including fatal cancers.
Moderator Bertram Pitt, MD, complimented Dr Dahlof on an important trial. He pointed out that many of the patients who entered the trial had poor blood pressure control and wondered how much blood pressure treatment contributed to the decline in deaths.
“I agree we are doing poorly in the control of blood pressure, but that is not an excuse for excluding giving this effective treatment to patients,” said Dr Dahlof. “Patients with multiple risks need multiple mechanisms of treatment.”
The report of Dr Dahlof’s study appeared on The Lancet web site at http://www.thelancet.com/journal/vol361/iss9364/full/llan.361.9364.original research.25148.1 (Lancet. 2003;361:1149–1158) right after his presentation.