TOURS, France, Feb. 18 -- Statin therapy significantly reduces the risk of atrial fibrillation in patients with a history of the condition and other high-risk groups, a meta-analysis has suggested.
Overall, statins reduced the odds ratio for atrial fibrillation by more than 60% compared with patients who did not receive the drugs, Laurent Fauchier, M.D., Ph.D., of Trousseau University Hospital Center, and colleagues reported in the Feb. 26 issue of the Journal of the American College of Cardiology.
Statins appeared to exert a greater impact in secondary prevention of atrial fibrillation rather than new-onset or postoperative atrial fibrillation.
"These results provide some evidence of the benefit of statins beyond their lipid-lowering activity," the authors concluded. "However, large-scale, prospective, randomized clinical trials are still needed to establish whether statins bring a similar benefit and are an appropriate therapeutic option in all subgroups of patients for the management of atrial fibrillation."
Observational studies have provided evidence of a protective effect of statins against atrial fibrillation. However, data were insufficient to provide a basis for recommending statin therapy to prevent the arrhythmia.
In an attempt to bring the potential atrial fibrillation benefit into sharper focus, Dr. Fauchier and colleagues searched for all randomized controlled trials of statins published from January 1980 through June 2007. They identified six trials involving 3,557 patients given statins versus placebo or a control therapy for treatment or prevention of atrial fibrillation.
Three studies examined the use of statins in patients with a history of paroxysmal atrial fibrillation or who were undergoing cardioversion for persistent atrial fibrillation. The remaining three trials evaluated statins in patients undergoing cardiac surgery or after acute coronary syndrome.
Overall, statin therapy was associated with a 61% decrease in the risk of atrial fibrillation (OR 0.39, 95% CI 0.18 to 0.85, P=0.02). Separate analyses suggested a more marked effect in the setting of secondary prevention (OR 0.33, 95% CI 0.10 to 1.03, P=0.06) than for new-onset or postoperative atrial fibrillation (OR 0.60, 95% CI 0.27 to 1.37, P=0.23).
The authors acknowledged they were unable to evaluate the possible impact of statin dose or the degree of LDL-lowering on arrhythmic events. They also noted that atrial fibrillation might arise from different factors in different patient subgroups, potentially making certain patients more responsive to an intervention compared with others.
Despite those limitations, Dr. Fauchier and colleagues concluded, "Use of statins was significantly associated with a decreased risk of incidence or recurrence of AF inpatients in sinus rhythm with a history of previous AF or undergoing cardiac surgery or after acute coronary syndrome."
The authors reported no disclosures.
Primary source: Journal of the American College of CardiologySource reference:Fauchier L, et al "Antiarrhythmic effect of statin therapy and atrial fibrillation: a meta-analysis of randomized controlled trials" J Am Coll Cardiol 2008; 51: DOI:10.1016/j.jacc.2007.09.063.
Showing posts with label Statin. Show all posts
Showing posts with label Statin. Show all posts
Monday, February 18, 2008
Wednesday, February 13, 2008
Do Statins Dull the Minds of Some Patients?
Wall Street Journal
February 12, 2008, 8:51 am
Posted by Jacob Goldstein
Here’s what the vice chairman of medicine at New York Presbyterian Hospital says about the effects of Lipitor on the cognitive function of some women: “This drug makes women stupid.”
Pfizer, which sells the cholesterol drug, says the pill has been tested in 400 clinical trials and racked up 145 million patient years of experience. The extensive data “do not establish a casual link between Lipitor and memory loss,” Pfizer says
And, as the WSJ’s Melinda Beck notes in today’s Health Journal column, the patient information sheet for the drug does not list cognitive issues such as memory loss or fuzzy thinking among the drug’s possible side effects. But the article also notes that anecdotal reports of a connection between statins and mental problems in some patients have been “rampant for years.”
The problem with anecdotal evidence, of course, is that it could always be coincidence masquerading as causality — the patients might have had memory problems even if they weren’t on the drug. And most cardiologists say the benefits of statins far outweigh any risks.
In any case, a clearer picture may be forthcoming: Researchers at the University of California at San Diego will soon complete a randomized controlled trial examining the effects of statins on thinking, mood, behavior and quality of life.
February 12, 2008, 8:51 am
Posted by Jacob Goldstein
Here’s what the vice chairman of medicine at New York Presbyterian Hospital says about the effects of Lipitor on the cognitive function of some women: “This drug makes women stupid.”
Pfizer, which sells the cholesterol drug, says the pill has been tested in 400 clinical trials and racked up 145 million patient years of experience. The extensive data “do not establish a casual link between Lipitor and memory loss,” Pfizer says
And, as the WSJ’s Melinda Beck notes in today’s Health Journal column, the patient information sheet for the drug does not list cognitive issues such as memory loss or fuzzy thinking among the drug’s possible side effects. But the article also notes that anecdotal reports of a connection between statins and mental problems in some patients have been “rampant for years.”
The problem with anecdotal evidence, of course, is that it could always be coincidence masquerading as causality — the patients might have had memory problems even if they weren’t on the drug. And most cardiologists say the benefits of statins far outweigh any risks.
In any case, a clearer picture may be forthcoming: Researchers at the University of California at San Diego will soon complete a randomized controlled trial examining the effects of statins on thinking, mood, behavior and quality of life.
Saturday, January 12, 2008
Meta-Analysis of Effect of Statin Treatment on Risk of Sudden Death
Meta-Analysis of Effect of Statin Treatment on Risk of Sudden Death
Title: Meta-Analysis of Effect of Statin Treatment on Risk of Sudden Death
Topic: Arrhythmias
Date Posted: 1/11/2008
Author(s): Levatesi G, Scarano M, Marfisi R, et al.
Citation: Am J Cardiol. 2007;100:1644-1650.
Study Question: Do statins prevent sudden death (SD)?
Methods: This was a meta-analysis of 10 randomized, controlled trials in which a statin was compared with placebo or no therapy. There were a total of 22,275 patients, with 11,136 randomly assigned to receive a statin. The mean age was 60 years, 81% were male, and 69% had a history of myocardial infarction. The mean duration of follow-up was 4.4 years.
Results: The incidence of SD was significantly lower in the statin group (3.0%) than in the control group (3.8%). The 19% reduction in relative risk of SD in the statin group was independent of the extent to which the plasma cholesterol level decreased.
Conclusions: Stains reduce the relative risk of SD by approximately 20% over 4 years of follow-up.
Perspective: A reduction in SD by statins is consistent with the results of implantable cardioverter defibrillator trials that have demonstrated a reduction in the risk of appropriate shocks in patients treated with a statin. There are several possible mechanisms by which statins might reduce the risk of malignant ventricular arrhythmias, including prevention of ischemia and indirect channel effects mediated by alterations in the lipid content of cell membranes. Fred Morady, M.D., F.A.C.C.
Statin therapy in diabetics supported
Statin therapy in diabetics supported
By Caroline Price
11 January 2008
Lancet 2008; 371: 117-125
MedWire News: Meta-analysis findings demonstrate that statin therapy should be considered in all individuals with diabetes if they are deemed at "sufficiently high" risk for vascular events, conclude the Cholesterol Treatment Trialists' (CTT) Collaborators in The Lancet.
An earlier CTT meta-analysis of 14 randomized trials of statin therapy showed that lowering low-density lipoprotein (LDL) cholesterol by 1 mmol/l reduces the risk of vascular events (myocardial infarction or coronary death, stroke, or coronary revascularization) by around one-fifth in a broad range of high-risk individuals, largely irrespective of baseline lipid levels and conditions, including diabetes.
For the current study, the CTT investigators conducted pre-specified analyses of the same 14 trials to determine whether individuals with diabetes derive the same benefits from statins as those without.
Uncertainties remain over the effects of statins in diabetic individuals on major coronary events, stroke, and the need for revascularization, and whether their benefits are worthwhile in those without a history of occlusive vascular disease, the team explains.
The researchers report that there were 3247 major vascular events over a mean follow-up of 4.3 years among the 18,686 participants who had diabetes.
These participants had a 9% reduction in all-cause mortality per mmol/l decrease in LDL cholesterol (relative risk [RR]=0.91, p=0.02). This reduction was similar in magnitude to the 13% RR reduction per mmol/l decrease in LDL cholesterol RR=0.87, p<0.0001) in the remaining 71,370 patients without diabetes, the researchers say.
The reduction in all-cause mortality reflected significant reductions in vascular mortality (0.87, p=0.008) and death due to coronary heart disease (0.88, p=0.03) per mmol/l reduction in LDL cholesterol in the diabetic individuals, with no significant effect on vascular mortality (RR=0.97).
There was a significant 21% reduction in major vascular events per mmol/l decrease in LDL cholesterol in both participants with and without diabetes.
Statin therapy was also associated with significant reductions in MI or coronary death, coronary revascularization, and stroke among the diabetic participants.
Finally, the proportional risk reductions for major vascular events among diabetic individuals were similar irrespective of history of vascular disease, gender, age, treated hypertension, body mass index, systolic or diastolic blood pressure, smoking history, and renal function.
The authors comment that the consistency of the reduction in major vascular events suggests that the benefit is likely to hold true in other populations with diabetes.
"Consequently, the absolute benefits in any specific population of patients may be best estimated by application of a reduction of about a fifth per mmol/l LDL cholesterol reduction to the relevant age-specific and sex-specific rates for that population," they write.
Journal
By Caroline Price
11 January 2008
Lancet 2008; 371: 117-125
MedWire News: Meta-analysis findings demonstrate that statin therapy should be considered in all individuals with diabetes if they are deemed at "sufficiently high" risk for vascular events, conclude the Cholesterol Treatment Trialists' (CTT) Collaborators in The Lancet.
An earlier CTT meta-analysis of 14 randomized trials of statin therapy showed that lowering low-density lipoprotein (LDL) cholesterol by 1 mmol/l reduces the risk of vascular events (myocardial infarction or coronary death, stroke, or coronary revascularization) by around one-fifth in a broad range of high-risk individuals, largely irrespective of baseline lipid levels and conditions, including diabetes.
For the current study, the CTT investigators conducted pre-specified analyses of the same 14 trials to determine whether individuals with diabetes derive the same benefits from statins as those without.
Uncertainties remain over the effects of statins in diabetic individuals on major coronary events, stroke, and the need for revascularization, and whether their benefits are worthwhile in those without a history of occlusive vascular disease, the team explains.
The researchers report that there were 3247 major vascular events over a mean follow-up of 4.3 years among the 18,686 participants who had diabetes.
These participants had a 9% reduction in all-cause mortality per mmol/l decrease in LDL cholesterol (relative risk [RR]=0.91, p=0.02). This reduction was similar in magnitude to the 13% RR reduction per mmol/l decrease in LDL cholesterol RR=0.87, p<0.0001) in the remaining 71,370 patients without diabetes, the researchers say.
The reduction in all-cause mortality reflected significant reductions in vascular mortality (0.87, p=0.008) and death due to coronary heart disease (0.88, p=0.03) per mmol/l reduction in LDL cholesterol in the diabetic individuals, with no significant effect on vascular mortality (RR=0.97).
There was a significant 21% reduction in major vascular events per mmol/l decrease in LDL cholesterol in both participants with and without diabetes.
Statin therapy was also associated with significant reductions in MI or coronary death, coronary revascularization, and stroke among the diabetic participants.
Finally, the proportional risk reductions for major vascular events among diabetic individuals were similar irrespective of history of vascular disease, gender, age, treated hypertension, body mass index, systolic or diastolic blood pressure, smoking history, and renal function.
The authors comment that the consistency of the reduction in major vascular events suggests that the benefit is likely to hold true in other populations with diabetes.
"Consequently, the absolute benefits in any specific population of patients may be best estimated by application of a reduction of about a fifth per mmol/l LDL cholesterol reduction to the relevant age-specific and sex-specific rates for that population," they write.
Journal
Friday, January 4, 2008
Statins for Secondary Prevention in Elderly Patients
Statins for Secondary Prevention in Elderly Patients
A Hierarchical Bayesian Meta-Analysis
Jonathan Afilalo, Gustavo Duque, Russell Steele, J. Wouter Jukema, Anton J.M. de Craen, and Mark J.
J Am Coll Cardiol Volume 51, Issue 1, January 1/8, 2008
Objectives: This study was designed to determine whether statins reduce all-cause mortality in elderly patients with coronary heart disease.
Background: Statins continue to be underutilized in elderly patients because evidence has not consistently shown that they reduce mortality.
Methods: We searched 5 electronic databases, the Internet, and conference proceedings to identify relevant trials. In addition, we obtained unpublished data for the elderly patient subgroups from 4 trials and for the secondary prevention subgroup from the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) trial. Inclusion criteria were randomized allocation to statin or placebo, documented coronary heart disease, 50 elderly patients (defined as age 65 years), and 6 months of follow-up. Data were analyzed with hierarchical Bayesian modeling.
Results: We included 9 trials encompassing 19,569 patients with an age range of 65 to 82 years. Pooled rates of all-cause mortality were 15.6% with statins and 18.7% with placebo. We estimated a relative risk reduction of 22% over 5 years (relative risk [RR] 0.78; 95% credible interval [CI] 0.65 to 0.89). Furthermore, statins reduced coronary heart disease mortality by 30% (RR 0.70; 95% CI 0.53 to 0.83), nonfatal myocardial infarction by 26% (RR 0.74; 95% CI 0.60 to 0.89), need for revascularization by 30% (RR 0.70; 95% CI 0.53 to 0.83), and stroke by 25% (RR 0.75; 95% CI 0.56 to 0.94). The posterior median estimate of the number needed to treat to save 1 life was 28 (95% CI 15 to 56).
Conclusions: Statins reduce all-cause mortality in elderly patients and the magnitude of this effect is substantially larger than had been previously estimated.
A Hierarchical Bayesian Meta-Analysis
Jonathan Afilalo, Gustavo Duque, Russell Steele, J. Wouter Jukema, Anton J.M. de Craen, and Mark J.
J Am Coll Cardiol Volume 51, Issue 1, January 1/8, 2008
Objectives: This study was designed to determine whether statins reduce all-cause mortality in elderly patients with coronary heart disease.
Background: Statins continue to be underutilized in elderly patients because evidence has not consistently shown that they reduce mortality.
Methods: We searched 5 electronic databases, the Internet, and conference proceedings to identify relevant trials. In addition, we obtained unpublished data for the elderly patient subgroups from 4 trials and for the secondary prevention subgroup from the PROSPER (PROspective Study of Pravastatin in the Elderly at Risk) trial. Inclusion criteria were randomized allocation to statin or placebo, documented coronary heart disease, 50 elderly patients (defined as age 65 years), and 6 months of follow-up. Data were analyzed with hierarchical Bayesian modeling.
Results: We included 9 trials encompassing 19,569 patients with an age range of 65 to 82 years. Pooled rates of all-cause mortality were 15.6% with statins and 18.7% with placebo. We estimated a relative risk reduction of 22% over 5 years (relative risk [RR] 0.78; 95% credible interval [CI] 0.65 to 0.89). Furthermore, statins reduced coronary heart disease mortality by 30% (RR 0.70; 95% CI 0.53 to 0.83), nonfatal myocardial infarction by 26% (RR 0.74; 95% CI 0.60 to 0.89), need for revascularization by 30% (RR 0.70; 95% CI 0.53 to 0.83), and stroke by 25% (RR 0.75; 95% CI 0.56 to 0.94). The posterior median estimate of the number needed to treat to save 1 life was 28 (95% CI 15 to 56).
Conclusions: Statins reduce all-cause mortality in elderly patients and the magnitude of this effect is substantially larger than had been previously estimated.
Monday, November 5, 2007
AHA - 2007: The ILLUMINATE trial, final analysis
Final results presented on cholesterol drug trial stopped in December
Late-Breaking Clinical Trials News Release 10
ORLANDO, Nov. 5 – Final analysis of a cholesterol drug trial that was halted early was presented as a late-breaking clinical trial at the American Heart Association’s Scientific Sessions 2007.
The ILLUMINATE trial was designed to test whether torcetrapib, in combination with atorvastatin, reduces major cardiovascular disease events when compared to atorvastatin alone.
But the trial was terminated in December 2006 because of “an imbalance of mortality and cardiovascular events” associated with the use of the drug. In the terminated trial, a 60 percent increase in deaths was observed among patients taking torcetrapib and atorvastatin versus those taking atorvastatin alone. The results did suggest any question about the safety of atorvastatin, a well-established therapy.
Torcetrapib is a cholesteryl ester transfer protein (CETP) inhibitor. CETP inhibitors are a class of drugs that increase blood levels of the “good” high density lipoprotein cholesterol (HDL-C).
Between August 2004 and December 2005, researchers randomized 15,067 men and women, ages 45-75 years old who were at high risk for cardiovascular disease events and eligible for statin treatment. Patients were considered high risk because of prior coronary heart disease, peripheral vascular disease, symptomatic carotid artery disease, or type 2 diabetes.
The use of torcetrapib in the ILLUMINATE trial was associated with: a predicted substantial (72 percent) increase in HDL-C (“good” cholesterol) and decrease (25 percent) in LDL-C (“bad” cholesterol); increased systolic blood pressure by 5.4 mmHg, decreased serum potassium, and increased serum sodium, bicarbonate and aldosterone (p<0.001 for each). An excess of major cardiovascular disease events (HR 1.25; p=0.001; 95% CI [1.09,1.44]) and deaths (HR=1.58; p=0.006; 95% CI [1.14,2.19]) was observed with torcetrapib use. The excess of deaths included both cardiovascular, and non-cardiovascular causes. Serious adverse events were reported by 16.4% and 15.0%, respectively, of subjects in the trorcetrpib with atorvastatin group and atorvastatin-only group (p=0.02).
“The adverse clinical outcome associated with the use of torcetrapib may have been the consequence of this off-target pharmacology,” said Philip Barter, M.D., Ph.D., lead investigator of the study and professor at The Heart Research Institute in Sydney, Australia. But the possibility of an adverse effect of CETP inhibition cannot be excluded by the results of the randomized trial.
“Post-hoc exploratory analyses are underway in an attempt to inform the design of any future studies aiming to investigate the potential clinical benefit of CETP inhibition,” Barter said.
Support for this study was provided by Pfizer.
Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.
Late-Breaking Clinical Trials News Release 10
ORLANDO, Nov. 5 – Final analysis of a cholesterol drug trial that was halted early was presented as a late-breaking clinical trial at the American Heart Association’s Scientific Sessions 2007.
The ILLUMINATE trial was designed to test whether torcetrapib, in combination with atorvastatin, reduces major cardiovascular disease events when compared to atorvastatin alone.
But the trial was terminated in December 2006 because of “an imbalance of mortality and cardiovascular events” associated with the use of the drug. In the terminated trial, a 60 percent increase in deaths was observed among patients taking torcetrapib and atorvastatin versus those taking atorvastatin alone. The results did suggest any question about the safety of atorvastatin, a well-established therapy.
Torcetrapib is a cholesteryl ester transfer protein (CETP) inhibitor. CETP inhibitors are a class of drugs that increase blood levels of the “good” high density lipoprotein cholesterol (HDL-C).
Between August 2004 and December 2005, researchers randomized 15,067 men and women, ages 45-75 years old who were at high risk for cardiovascular disease events and eligible for statin treatment. Patients were considered high risk because of prior coronary heart disease, peripheral vascular disease, symptomatic carotid artery disease, or type 2 diabetes.
The use of torcetrapib in the ILLUMINATE trial was associated with: a predicted substantial (72 percent) increase in HDL-C (“good” cholesterol) and decrease (25 percent) in LDL-C (“bad” cholesterol); increased systolic blood pressure by 5.4 mmHg, decreased serum potassium, and increased serum sodium, bicarbonate and aldosterone (p<0.001 for each). An excess of major cardiovascular disease events (HR 1.25; p=0.001; 95% CI [1.09,1.44]) and deaths (HR=1.58; p=0.006; 95% CI [1.14,2.19]) was observed with torcetrapib use. The excess of deaths included both cardiovascular, and non-cardiovascular causes. Serious adverse events were reported by 16.4% and 15.0%, respectively, of subjects in the trorcetrpib with atorvastatin group and atorvastatin-only group (p=0.02).
“The adverse clinical outcome associated with the use of torcetrapib may have been the consequence of this off-target pharmacology,” said Philip Barter, M.D., Ph.D., lead investigator of the study and professor at The Heart Research Institute in Sydney, Australia. But the possibility of an adverse effect of CETP inhibition cannot be excluded by the results of the randomized trial.
“Post-hoc exploratory analyses are underway in an attempt to inform the design of any future studies aiming to investigate the potential clinical benefit of CETP inhibition,” Barter said.
Support for this study was provided by Pfizer.
Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.
AHA - 2007: Researchers examine benefits of statins for heart failure patients
Researchers examine benefits of statins for heart failure patients
Late-Breaking Clinical Trials News Release 9
ORLANDO, Nov. 5 – Results of a clinical trial to determine the efficacy and safety of adding rosuvastatin 10 mg to optimal therapy in patients with ischemic heart disease and systolic heart failure were presented as late-breaking research at the American Heart Association’s Scientific Sessions 2007.
“Because patients with symptomatic heart failure were excluded from past placebo-controlled trials with statins, the benefits and risks of statins in the treatment of heart failure remain uncertain,” said Åke Hjalmarson, an investigator in the Sweden-based Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). CORONA was designed to clarify the role of statin therapy in treating patients with systolic heart failure.
CORONA is a randomized, double-blind, placebo-controlled study of 5,011 men and women with chronic symptomatic systolic heart failure (caused by coronary artery disease). Average patient age was 73 years, 24 percent were women, 37 percent were in New York Heart Association (NYHA) class II heart failure and 62 percent in class III. The average ejection fraction (EF) was 31 percent. Ejection fraction is a measure of how much blood the heart’s left ventricle pumps out with each contraction. The normal EF is 50 percent or greater.
The average total cholesterol among patients was 200 mg/dL. Participants were not already taking cholesterol-lowering drugs. Patient medical histories included 60 percent with a history of heart attack, 63 percent with hypertension and 30 percent with diabetes.
“These patients were well-treated for their heart failure,” Hjalmarson said, with 87 percent on loop or thiazide diuretics, 39 percent on aldosterone antagonists, 91 percent taking an ACE inhibitor or AT-I blocker, 75 percent taking a beta-blocker, and 33 percent taking digitalis. In addition, 51 percent were taking aspirin and 36 percent taking anticoagulants.
Patients were randomized to receive either rosuvastatin (10 mg) or placebo along with all other medications. Average follow-up time was 2.5 years.
The primary objective of CORONA was to determine whether rosuvastatin reduces the number of patients suffering from cardiovascular death, non-fatal heart attack or non-fatal stroke.
Support for this study was provided by AstraZeneca.
Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.
Late-Breaking Clinical Trials News Release 9
ORLANDO, Nov. 5 – Results of a clinical trial to determine the efficacy and safety of adding rosuvastatin 10 mg to optimal therapy in patients with ischemic heart disease and systolic heart failure were presented as late-breaking research at the American Heart Association’s Scientific Sessions 2007.
“Because patients with symptomatic heart failure were excluded from past placebo-controlled trials with statins, the benefits and risks of statins in the treatment of heart failure remain uncertain,” said Åke Hjalmarson, an investigator in the Sweden-based Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). CORONA was designed to clarify the role of statin therapy in treating patients with systolic heart failure.
CORONA is a randomized, double-blind, placebo-controlled study of 5,011 men and women with chronic symptomatic systolic heart failure (caused by coronary artery disease). Average patient age was 73 years, 24 percent were women, 37 percent were in New York Heart Association (NYHA) class II heart failure and 62 percent in class III. The average ejection fraction (EF) was 31 percent. Ejection fraction is a measure of how much blood the heart’s left ventricle pumps out with each contraction. The normal EF is 50 percent or greater.
The average total cholesterol among patients was 200 mg/dL. Participants were not already taking cholesterol-lowering drugs. Patient medical histories included 60 percent with a history of heart attack, 63 percent with hypertension and 30 percent with diabetes.
“These patients were well-treated for their heart failure,” Hjalmarson said, with 87 percent on loop or thiazide diuretics, 39 percent on aldosterone antagonists, 91 percent taking an ACE inhibitor or AT-I blocker, 75 percent taking a beta-blocker, and 33 percent taking digitalis. In addition, 51 percent were taking aspirin and 36 percent taking anticoagulants.
Patients were randomized to receive either rosuvastatin (10 mg) or placebo along with all other medications. Average follow-up time was 2.5 years.
The primary objective of CORONA was to determine whether rosuvastatin reduces the number of patients suffering from cardiovascular death, non-fatal heart attack or non-fatal stroke.
Support for this study was provided by AstraZeneca.
Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.
Friday, October 12, 2007
Long-Term Follow-up of the West of Scotland Coronary Prevention Study
Long-Term Follow-up of the West of Scotland Coronary Prevention Study
Ford I et al. for the West of Scotland Coronary Prevention Study Group. Long-term follow-up of the West of Scotland Coronary Prevention Study.
N Engl J Med 2007 Oct 11; 357:1477.
ABSTRACT
Background The West of Scotland Coronary Prevention Study was a randomized clinical trial comparing pravastatin with placebo in men with hypercholesterolemia who did not have a history of myocardial infarction, with an average follow-up of approximately 5 years. The combined outcome of death from definite coronary heart disease or definite nonfatal myocardial infarction was reduced from 7.9 to 5.5% (P<0.001) in the treatment group. Extended follow-up data were obtained for approximately 10 years after completion of the trial.
Methods For the survivors of the trial, all deaths, hospitalizations and deaths due to coronary events and stroke, and incident cancers and deaths from cancer were tracked with the use of a national computerized record-linkage system. The results were analyzed with time-to-event analyses and use of Cox proportional-hazards models.
Results Five years after the trial ended, 38.7% of the original statin group and 35.2% of the original placebo group were being treated with a statin. In the period approximately 10 years after completion of the trial, the risk of death from coronary heart disease or nonfatal myocardial infarction was 10.3% in the placebo group and 8.6% in the pravastatin group (P=0.02); over the entire follow-up period, the rate was 15.5% in the placebo group and 11.8% in the pravastatin group (P<0.001). Similar percentage reductions were seen in the combined rate of death from coronary heart disease and hospitalization for coronary events for both periods. The rate of death from cardiovascular causes was reduced (P=0.01), as was the rate of death from any cause (P=0.03), over the entire follow-up period. There were no excess deaths from noncardiovascular causes or excess fatal or incident cancers.
Conclusions In this analysis, 5 years of treatment with pravastatin was associated with a significant reduction in coronary events for a subsequent 10 years in men with hypercholesterolemia who did not have a history of myocardial infarction.
The West of Scotland Coronary Prevention Study: Long-Term Results
Published in Journal Watch Cardiology October 10, 2007
The benefits of statins for primary prevention of coronary heart disease stand the test of time.
Results published in 1995 from the West of Scotland Coronary Prevention Study (WOSCOPS), a randomized, double-blind, placebo-controlled clinical trial of pravastatin in middle-aged men without a history of MI, demonstrated a significant benefit after approximately 5 years of treatment (Journal Watch Cardiology Dec 1 1995). Now, the WOSCOPS investigators report outcomes over the subsequent 10 years.
About one third of the study subjects took statins during the post-trial period; the percentages were slightly higher in those who were originally randomized to pravastatin. During follow-up (mean, 13.2 years for cancer and 14.7 years for other outcomes), 18.8% of the participants originally assigned to pravastatin died, compared with 20.5% of those originally assigned to placebo. During the entire 15-year study period, the original pravastatin group had significant reductions in death from all causes (hazard ratio, 0.88), death from cardiovascular causes (HR, 0.81), and the composite of death from coronary heart disease and nonfatal MI (HR, 0.73), compared with the original placebo group. The greatest benefits with pravastatin occurred during the trial period — e.g., the reduction in death from cardiovascular causes was 34% during the trial and 14% in the post-trial period. Pravastatin treatment was not associated with an increase in cancer rates.
Comment: This study extends the findings of a classic statin trial: The benefits manifested during the trial were maintained — and perhaps expanded — through 10 years of follow-up. These results add to an already large literature supporting the value of statins for secondary prevention of coronary heart disease.
Ford I et al. for the West of Scotland Coronary Prevention Study Group. Long-term follow-up of the West of Scotland Coronary Prevention Study.
N Engl J Med 2007 Oct 11; 357:1477.
ABSTRACT
Background The West of Scotland Coronary Prevention Study was a randomized clinical trial comparing pravastatin with placebo in men with hypercholesterolemia who did not have a history of myocardial infarction, with an average follow-up of approximately 5 years. The combined outcome of death from definite coronary heart disease or definite nonfatal myocardial infarction was reduced from 7.9 to 5.5% (P<0.001) in the treatment group. Extended follow-up data were obtained for approximately 10 years after completion of the trial.
Methods For the survivors of the trial, all deaths, hospitalizations and deaths due to coronary events and stroke, and incident cancers and deaths from cancer were tracked with the use of a national computerized record-linkage system. The results were analyzed with time-to-event analyses and use of Cox proportional-hazards models.
Results Five years after the trial ended, 38.7% of the original statin group and 35.2% of the original placebo group were being treated with a statin. In the period approximately 10 years after completion of the trial, the risk of death from coronary heart disease or nonfatal myocardial infarction was 10.3% in the placebo group and 8.6% in the pravastatin group (P=0.02); over the entire follow-up period, the rate was 15.5% in the placebo group and 11.8% in the pravastatin group (P<0.001). Similar percentage reductions were seen in the combined rate of death from coronary heart disease and hospitalization for coronary events for both periods. The rate of death from cardiovascular causes was reduced (P=0.01), as was the rate of death from any cause (P=0.03), over the entire follow-up period. There were no excess deaths from noncardiovascular causes or excess fatal or incident cancers.
Conclusions In this analysis, 5 years of treatment with pravastatin was associated with a significant reduction in coronary events for a subsequent 10 years in men with hypercholesterolemia who did not have a history of myocardial infarction.
The West of Scotland Coronary Prevention Study: Long-Term Results
Published in Journal Watch Cardiology October 10, 2007
The benefits of statins for primary prevention of coronary heart disease stand the test of time.
Results published in 1995 from the West of Scotland Coronary Prevention Study (WOSCOPS), a randomized, double-blind, placebo-controlled clinical trial of pravastatin in middle-aged men without a history of MI, demonstrated a significant benefit after approximately 5 years of treatment (Journal Watch Cardiology Dec 1 1995). Now, the WOSCOPS investigators report outcomes over the subsequent 10 years.
About one third of the study subjects took statins during the post-trial period; the percentages were slightly higher in those who were originally randomized to pravastatin. During follow-up (mean, 13.2 years for cancer and 14.7 years for other outcomes), 18.8% of the participants originally assigned to pravastatin died, compared with 20.5% of those originally assigned to placebo. During the entire 15-year study period, the original pravastatin group had significant reductions in death from all causes (hazard ratio, 0.88), death from cardiovascular causes (HR, 0.81), and the composite of death from coronary heart disease and nonfatal MI (HR, 0.73), compared with the original placebo group. The greatest benefits with pravastatin occurred during the trial period — e.g., the reduction in death from cardiovascular causes was 34% during the trial and 14% in the post-trial period. Pravastatin treatment was not associated with an increase in cancer rates.
Comment: This study extends the findings of a classic statin trial: The benefits manifested during the trial were maintained — and perhaps expanded — through 10 years of follow-up. These results add to an already large literature supporting the value of statins for secondary prevention of coronary heart disease.
Tuesday, October 9, 2007
The Case for Early Statin Therapy After AMI
The Case for Early Statin Therapy After AMI
A Japanese study suggests that initiating standard statin therapy immediately after patients suffer an acute myocardial infarction (AMI) appears to decrease long-term mortality and subsequent cardiac events. Among AMI patients, the researchers found that male patients older than 60 and patients with high LDL cholesterol levels (155 mg/dL or greater) appeared to benefit most from early statin therapy. Early statin therapy strongly correlated with a lower risk of cardiovascular death, less recurrence of AMI, and less heart failure. “The hazard ratio for statin therapy was 0.64 throughout the study.” The study was published in the June 1, 2007 American Journal of Cardiology.
An abstract of the study is available at www.sciencedirect.com/
A Japanese study suggests that initiating standard statin therapy immediately after patients suffer an acute myocardial infarction (AMI) appears to decrease long-term mortality and subsequent cardiac events. Among AMI patients, the researchers found that male patients older than 60 and patients with high LDL cholesterol levels (155 mg/dL or greater) appeared to benefit most from early statin therapy. Early statin therapy strongly correlated with a lower risk of cardiovascular death, less recurrence of AMI, and less heart failure. “The hazard ratio for statin therapy was 0.64 throughout the study.” The study was published in the June 1, 2007 American Journal of Cardiology.
An abstract of the study is available at www.sciencedirect.com/
Thursday, August 30, 2007
Statin treatment withdrawal in ischemic stroke: a controlled randomized study
Statin treatment withdrawal in ischemic stroke: a controlled randomized study.
Neurology. 2007 Aug 28;69(9):904-10.
Blanco M, Nombela F, Castellanos M, Rodriguez-Yáñez M, García-Gil M, Leira R, Lizasoain I, Serena J, Vivancos J, Moro MA, Dávalos A, Castillo J.
Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
BACKGROUND: Pretreatment with statins has been shown to reduce brain injury in cerebral ischemia. In this controlled randomized study, we investigated the influence of statin pretreatment and its withdrawal on the outcome of acute ischemic stroke patients.
METHODS: From 215 patients admitted within 24 hours of a hemispheric ischemic stroke, 89 patients on chronic statin treatment were randomly assigned either to statin withdrawal for the first 3 days after admission (n = 46) or to immediately receive atorvastatin 20 mg/day (n = 43). The primary outcome event was death or dependency (modified Rankin Scale [mRS] score > 2) at 3 months. Early neurologic deterioration (END) and infarct volume at days 4 to 7 were secondary outcome variables. In a secondary analysis, outcome variables were compared with the nonrandomized patients without previous statin therapy (n = 126).
RESULTS: Patients with statin withdrawal showed a higher frequency of mRS score > 2 at the end of follow-up (60.0% vs 39.0%; p = 0.043), END (65.2% vs 20.9%; p < 0.0001), and greater infarct volume (74 [45, 126] vs 26 [12, 70] mL; p = 0.002) compared with the non-statin-withdrawal group. Statin withdrawal was associated with a 4.66 (1.46 to 14.91)-fold increase in the risk of death or dependency, a 8.67 (3.05 to 24.63)-fold increase in the risk of END, and an increase in mean infarct volume of 37.63 mL (SE 10.01; p < 0.001) after adjusting for age and baseline stroke severity. Compared with patients without previous treatment with statins, statin withdrawal was associated with a 19.01 (1.96 to 184.09)-fold increase in the risk of END and an increase in mean infarct volume of 43.51 mL (SE 21.91; p = 0.048).
CONCLUSION: Statin withdrawal is associated with increased risk of death or dependency at 90 days. Hence, this treatment should be continued in the acute phase of ischemic stroke.
Neurology. 2007 Aug 28;69(9):904-10.
Blanco M, Nombela F, Castellanos M, Rodriguez-Yáñez M, García-Gil M, Leira R, Lizasoain I, Serena J, Vivancos J, Moro MA, Dávalos A, Castillo J.
Department of Neurology, Hospital Clínico Universitario, Universidad de Santiago de Compostela, Santiago de Compostela, Spain.
BACKGROUND: Pretreatment with statins has been shown to reduce brain injury in cerebral ischemia. In this controlled randomized study, we investigated the influence of statin pretreatment and its withdrawal on the outcome of acute ischemic stroke patients.
METHODS: From 215 patients admitted within 24 hours of a hemispheric ischemic stroke, 89 patients on chronic statin treatment were randomly assigned either to statin withdrawal for the first 3 days after admission (n = 46) or to immediately receive atorvastatin 20 mg/day (n = 43). The primary outcome event was death or dependency (modified Rankin Scale [mRS] score > 2) at 3 months. Early neurologic deterioration (END) and infarct volume at days 4 to 7 were secondary outcome variables. In a secondary analysis, outcome variables were compared with the nonrandomized patients without previous statin therapy (n = 126).
RESULTS: Patients with statin withdrawal showed a higher frequency of mRS score > 2 at the end of follow-up (60.0% vs 39.0%; p = 0.043), END (65.2% vs 20.9%; p < 0.0001), and greater infarct volume (74 [45, 126] vs 26 [12, 70] mL; p = 0.002) compared with the non-statin-withdrawal group. Statin withdrawal was associated with a 4.66 (1.46 to 14.91)-fold increase in the risk of death or dependency, a 8.67 (3.05 to 24.63)-fold increase in the risk of END, and an increase in mean infarct volume of 37.63 mL (SE 10.01; p < 0.001) after adjusting for age and baseline stroke severity. Compared with patients without previous treatment with statins, statin withdrawal was associated with a 19.01 (1.96 to 184.09)-fold increase in the risk of END and an increase in mean infarct volume of 43.51 mL (SE 21.91; p = 0.048).
CONCLUSION: Statin withdrawal is associated with increased risk of death or dependency at 90 days. Hence, this treatment should be continued in the acute phase of ischemic stroke.
Monday, August 27, 2007
Statins and Alzheimer's disease
Heart Drug May Hold Off Alzheimer's
By Alice Park
The long goodbye of Alzheimer's disease may become increasingly common as our population ages in coming years, but scientists in Seattle provide reassuring evidence that at least some of the disease's gradual mental decline can be held off with, of all things, cholesterol-lowering drugs.
In a study of 110 elderly volunteers, aged 65 to 79, who donated their brains for research and whose cognitive functions were monitored over several years prior to their death, scientists led by Dr. Eric Larson of the Group Health Center for Health Studies found that those who had taken statin drugs to lower their cholesterol had fewer nerve-damaging plaques and tangles — protein deposits that form in and around neurons — in their brains than those not taking the medications. Buildup of these protein plaques and tangles are the hallmark of Alzheimer's disease; they inexorably disrupt the critical connections between neurons that govern thought processes and sabotage everything from the storage and retrieval of memories to learning and language skills.
The new findings are the latest and most definitive results linking the popular statin drugs to Alzheimer's. Earlier studies had produced conflicting results: some found that statins reduced the risk of the brain disorder, while others found no effect. Larson's study is the first to directly compare the brains, on autopsy, of statin users and non-users (Alzheimer's can be conclusively diagnosed only after death, when pathologists confirm the presence of the plaques and tangles in the brain). "This data does give us some additional hope that statins may turn out to have a useful relationship in slowing Alzheimer's disease," says William Thies, vice president of medical and scientific relations of the Alzheimer's Association.
How do cholesterol-lowering drugs work on the brain? As experts learn more about Alzheimer's, they believe that it's less a disease of the brain than of the vasculature, or blood vessel system. It turns out that many of the risk factors for Alzheimer's are the same ones for heart disease, and that the build up of protein in the brain is not unlike the gradual accumulation of plaque in the heart vessels. "We are learning that Alzheimer's disease isn't just plaques and tangles appearing through a series of biochemical processes, but that vascular stress may play a role in their development," says Larson. "Anything we can do to lower the vascular risk profile could lower the risk of Alzheimer's." Statins, then, could be inhibiting the development of Alzheimer's by keeping the brain's neural highways free of potentially bottlenecking protein plaques. In addition, says Larson, statins may be working on a more molecular level, by actually blocking the formation of the sticky, fibrous tangles that can jam nerve connections.
To learn more about exactly how statins could be thwarting the Alzheimer's disease process, Larson acknowledges that the first step involves having another, independent group replicate his team's findings. In the meantime, he plans to continue his study by adding more volunteers. Within the next year, Thies expects two more trials to produce results and hopefully solidify the effect statins have on the brain.
By Alice Park
The long goodbye of Alzheimer's disease may become increasingly common as our population ages in coming years, but scientists in Seattle provide reassuring evidence that at least some of the disease's gradual mental decline can be held off with, of all things, cholesterol-lowering drugs.
In a study of 110 elderly volunteers, aged 65 to 79, who donated their brains for research and whose cognitive functions were monitored over several years prior to their death, scientists led by Dr. Eric Larson of the Group Health Center for Health Studies found that those who had taken statin drugs to lower their cholesterol had fewer nerve-damaging plaques and tangles — protein deposits that form in and around neurons — in their brains than those not taking the medications. Buildup of these protein plaques and tangles are the hallmark of Alzheimer's disease; they inexorably disrupt the critical connections between neurons that govern thought processes and sabotage everything from the storage and retrieval of memories to learning and language skills.
The new findings are the latest and most definitive results linking the popular statin drugs to Alzheimer's. Earlier studies had produced conflicting results: some found that statins reduced the risk of the brain disorder, while others found no effect. Larson's study is the first to directly compare the brains, on autopsy, of statin users and non-users (Alzheimer's can be conclusively diagnosed only after death, when pathologists confirm the presence of the plaques and tangles in the brain). "This data does give us some additional hope that statins may turn out to have a useful relationship in slowing Alzheimer's disease," says William Thies, vice president of medical and scientific relations of the Alzheimer's Association.
How do cholesterol-lowering drugs work on the brain? As experts learn more about Alzheimer's, they believe that it's less a disease of the brain than of the vasculature, or blood vessel system. It turns out that many of the risk factors for Alzheimer's are the same ones for heart disease, and that the build up of protein in the brain is not unlike the gradual accumulation of plaque in the heart vessels. "We are learning that Alzheimer's disease isn't just plaques and tangles appearing through a series of biochemical processes, but that vascular stress may play a role in their development," says Larson. "Anything we can do to lower the vascular risk profile could lower the risk of Alzheimer's." Statins, then, could be inhibiting the development of Alzheimer's by keeping the brain's neural highways free of potentially bottlenecking protein plaques. In addition, says Larson, statins may be working on a more molecular level, by actually blocking the formation of the sticky, fibrous tangles that can jam nerve connections.
To learn more about exactly how statins could be thwarting the Alzheimer's disease process, Larson acknowledges that the first step involves having another, independent group replicate his team's findings. In the meantime, he plans to continue his study by adding more volunteers. Within the next year, Thies expects two more trials to produce results and hopefully solidify the effect statins have on the brain.
Wednesday, August 8, 2007
Statin Treatment in Children With Familial Hypercholesterolemia
Statin Treatment in Children With Familial Hypercholesterolemia
The Younger, the Better
Published online before print July 30, 2007, doi:10.1161/CIRCULATIONAHA.106.671016
Jessica Rodenburg, MD, PhD; Maud N. Vissers, PhD; Albert Wiegman, MD, PhD; A. S. Paul van Trotsenburg, MD, PhD; Anouk van der Graaf, MD; Eric de Groot, MD, PhD; Frits A. Wijburg, MD, PhD; John J.P. Kastelein, MD, PhD; Barbara A. Hutten, PhD
From the Departments of Vascular Medicine (J.R., M.N.V., A.v.d.G., E.d.G., J.J.P.K.), Paediatrics (A.W., A.S.P.v.T., F.A.W.), and Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Background— We previously demonstrated in a randomized placebo-controlled trial that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8- to 18-year-old children with familial hypercholesterolemia. Subsequently, we continued to follow up these children to explore the relation between the age of statin initiation and carotid IMT after follow-up on statin treatment. We also examined safety aspects of statin therapy during this long-term follow-up.
Methods and Results— All 214 children who initially participated in the previous placebo-controlled study were eligible for the follow-up study. After completion of the placebo-controlled study, all children continued treatment with pravastatin 20 or 40 mg, depending on their age. Blood samples were taken on a regular basis for lipids and safety parameters, and a carotid IMT measurement was performed after an average treatment period of 4.5 years. Follow-up data for 186 children were available for the statistical analyses. Multivariate analyses revealed that age at statin initiation was an independent predictor for carotid IMT after follow-up with adjustment for carotid IMT at initiation of statin treatment, sex, and duration of treatment. Early initiation of statin treatment was associated with a subsequently smaller IMT. Furthermore, no serious laboratory adverse events were reported during follow-up, and statin treatment had no untoward effects on sexual maturation.
Conclusions— These data indicate that early initiation of statin treatment delays the progression of carotid IMT in adolescents and young adults. The present study shows for the first time that early initiation of statin therapy in children with familial hypercholesterolemia might be beneficial in the prevention of atherosclerosis in adolescence.
Primary source:
Circulation: Journal of the American Heart AssociationSource reference: Rodenburg J, et al "Statin Treatment in Children With Familial Hypercholesterolemia: The Younger, the Better" Circulation 2007;116: 664-668.
The Younger, the Better
Published online before print July 30, 2007, doi:10.1161/CIRCULATIONAHA.106.671016
Jessica Rodenburg, MD, PhD; Maud N. Vissers, PhD; Albert Wiegman, MD, PhD; A. S. Paul van Trotsenburg, MD, PhD; Anouk van der Graaf, MD; Eric de Groot, MD, PhD; Frits A. Wijburg, MD, PhD; John J.P. Kastelein, MD, PhD; Barbara A. Hutten, PhD
From the Departments of Vascular Medicine (J.R., M.N.V., A.v.d.G., E.d.G., J.J.P.K.), Paediatrics (A.W., A.S.P.v.T., F.A.W.), and Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Background— We previously demonstrated in a randomized placebo-controlled trial that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8- to 18-year-old children with familial hypercholesterolemia. Subsequently, we continued to follow up these children to explore the relation between the age of statin initiation and carotid IMT after follow-up on statin treatment. We also examined safety aspects of statin therapy during this long-term follow-up.
Methods and Results— All 214 children who initially participated in the previous placebo-controlled study were eligible for the follow-up study. After completion of the placebo-controlled study, all children continued treatment with pravastatin 20 or 40 mg, depending on their age. Blood samples were taken on a regular basis for lipids and safety parameters, and a carotid IMT measurement was performed after an average treatment period of 4.5 years. Follow-up data for 186 children were available for the statistical analyses. Multivariate analyses revealed that age at statin initiation was an independent predictor for carotid IMT after follow-up with adjustment for carotid IMT at initiation of statin treatment, sex, and duration of treatment. Early initiation of statin treatment was associated with a subsequently smaller IMT. Furthermore, no serious laboratory adverse events were reported during follow-up, and statin treatment had no untoward effects on sexual maturation.
Conclusions— These data indicate that early initiation of statin treatment delays the progression of carotid IMT in adolescents and young adults. The present study shows for the first time that early initiation of statin therapy in children with familial hypercholesterolemia might be beneficial in the prevention of atherosclerosis in adolescence.
Primary source:
Circulation: Journal of the American Heart AssociationSource reference: Rodenburg J, et al "Statin Treatment in Children With Familial Hypercholesterolemia: The Younger, the Better" Circulation 2007;116: 664-668.
Tuesday, July 24, 2007
Low Cholesterol Levels And Cancer
Low Cholesterol Levels And Cancer
Millions of Americans take statins to lower their cholesterol, but how low should you go" A number of scientific studies support the benefits of lowering low-density lipoprotein (LDL) cholesterol, and achieving low LDL cholesterol levels is one of the most important steps in preventing heart disease. New research, however, provides evidence for an association between low LDL levels and cancer risk.
The authors of the study, reported in the July 31, 2007, issue of the Journal of the American College of Cardiology (JACC), set out to understand how and why statins cause side effects, especially damage to the liver and muscle cells. The study findings support taking multiple medications rather than high-dose statins to minimize those side effects. The scientists did not expect to find the increased cancer risk (one additional incident per 1,000 patients) from low LDL levels, and additional studies have already begun to investigate this potential risk further. A key component in future studies will be to confirm the risk and to identify whether the risk may be a side effect of statins or just low LDL.
This analysis doesnt implicate the statin in increasing the risk of cancer, said lead author Richard H. Karas, M.D., F.A.C.C., professor of medicine at Tufts University School of Medicine. The demonstrated benefits of statins in lowering the risk of heart disease remain clear; however, certain aspects of lowering LDL with statins remain controversial and merit further research.
The scientists found one additional incident of cancer per 1,000 patients with low LDL levels when in comparison to patients with higher LDL levels. In their evaluation of randomized controlled statin trials published before November 2005, the scientists looked at 13 therapy arms consisting of 41,173 patients.
Scientists assessed absolute change and percentage of change in LDL reduction and the resulting achieved LDL levels in relation to rates of newly diagnosed cancer in each therapy arm. They also looked at the relationship between low, intermediate and high doses of statins and rates of newly diagnosed cancer. Eventhough they did not find a relationship between percent of change and absolute change in LDL levels, they observed higher rates of newly diagnosed cancer among patients with lower achieved LDL levels. In addition, the new cancers were not of any specific type or location.
Recent data from large-scale statin trials have shown that more intensive LDL lowering can provide significant cardiovascular benefits to higher-risk patients. In response to these findings, recent national guidelines have advocated for lower LDL goals and higher doses of statins to reach them. However, informal observations linking intensive LDL lowering and higher occurence rate of reported health problems, including liver and muscle toxicity and cancer, has introduced some concern over the safety of such therapys.
These concerns in part prompted the current study. However, the current findings are not definitive, as limitations of the study show. Scientists performed their analysis from summary data taken directly from published manuscripts of each trial. An analysis based on data for each individual patient would have yielded more specific and potentially more compelling results, said Dr. Karas.
These current findings provide insufficient evidence that there is any problem with LDL lowering that outweighs its significant benefits on vascular disease, said John C. La Rosa, M.D., who wrote an accompanying editorial in the July 31 issue of JACC. However, we must continue to be vigilant in ensuring that its benefit clearly outweighs its risk.
Eventhough the cancer risk was surprising, the scientists primarily sought to determine how and why statins cause side effects, especially damage to the liver and muscle cells. For this portion of the study, scientists analyzed 23 statin therapy arms that included 75,317 patients with a combined 309,506 years of follow up. A link between LDL lowering and liver or muscle irritation was not found. However, liver toxicity levels increased with higher statin dosage. Based on their findings, the scientists concluded that moderate-dose treatment with multiple medications including statins may prove to be preferable to high-dose treatment with statins alone. Dr. Karas emphasized that patients are advised to continue their statin therapys and, as always, consult their doctor before discontinuing use of any medication.
While these results raise important new questions about statin use, they do not demonstrate a causal relationship between statins and cancer, said James Dove, M.D., F.A.C.C., president of the American College of Cardiology. This study is hypothesis-generating, not hypothesis-proving.
Tuesday, April 17, 2007
ILLUSTRATE - Considerações
Title: Effect of Torcetrapib on the Progression of Coronary AtherosclerosisNissen SE, Tardif JC, Nicholls SJ, et al., on behalf of the ILLUSTRATE Investigators.
Citation: N Engl J Med. 2007;356:1304-1316.
Study Question: Does torcetrapib, a novel cholesteryl ester transfer protein (CETP) inhibitor that raises high-density lipoprotein cholesterol (HDL-C) by more than 50%, impact progression of coronary atherosclerosis?
Methods: A total of 1,188 patients with coronary disease underwent intravascular ultrasonography (IVUS). After treatment with atorvastatin to reduce levels of low-density lipoprotein cholesterol (LDL-C) to <100 mg/dl (2.59 mmol/L), patients were randomly assigned to receive either atorvastatin monotherapy or atorvastatin plus 60 mg of torcetrapib daily. After 24 months, disease progression was measured by repeated IVUS in 910 patients (77%). Each target site for the primary analysis was required to have <50% obstruction throughout a segment of 40 mm or longer.
Results: Mean age was 57 years, 70% were men, and 91% were on a statin at baseline. Baseline mean LDL-C was 84 mg/dl and HDL-C was 45.5 mg/dl, and median LDL-C:HDL-C was 1.89. After 24 months, as compared with atorvastatin monotherapy, the effect of torcetrapib–atorvastatin therapy was an approximate 61% relative increase in HDL-C (43.9 mg/dl vs. 72.1 mg/dl) and a 20% relative decrease in LDL-C, reaching a ratio of LDL-C to HDL-C of <1.0. Torcetrapib was also associated with an increase in systolic blood pressure of 4.6 mm Hg. The percent atheroma volume (the primary efficacy measure) increased by 0.19% in the atorvastatin-only group and by 0.12% in the torcetrapib–atorvastatin group (p = 0.72). A secondary measure, the change in normalized atheroma volume, showed a small favorable effect for torcetrapib (p = 0.02), but there was no significant difference in the change in atheroma volume for the most diseased vessel segment.
Conclusions: The CETP inhibitor torcetrapib was associated with a substantial increase in HDL-C and decrease in LDL-C. It was also associated with an increase in blood pressure, and there was no significant decrease in the progression of coronary atherosclerosis. The lack of efficacy may be related to the mechanism of action of this drug class or to molecule-specific adverse effects.
Perspective: Previous similar IVUS studies have shown that intense lowering of LDL-C by statins decreases the total atheroma volume by as much as 14.7 mm3 at 24 months, and the infusion of A-1 Milano resulted in a 14.1 mm3 reduction in atheroma volume at 1 month. It would appear that increasing HDL particle cholesterol content with a CETP inhibitor does not result in better functioning HDL particles, and there are experimental data that these cholesterol-rich HDL particles may have proinflammatory effects. The clinical morbidity–mortality trial of torcetrapib–atorvastatin was prematurely terminated because of an increase in event rates that might be explained by both the increase in systolic blood pressure and dysfunctional HDL particles. In addition to niacin, several novel drugs/devices are currently being studied in randomized trials to determine their effect on atherosclerosis progression and events. Melvyn Rubenfire, M.D., F.A.C.C.
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