Study Locates Cholesterol Genes; Finds Surprises About Good, Bad Cholesterol
ScienceDaily (Jan. 17, 2008) — An international study of 20,000 people found seven new genes that influence blood cholesterol levels, a major factor in heart disease, and confirmed 11 other genes previously thought to influence cholesterol.
full story
Showing posts with label Cholesterol. Show all posts
Showing posts with label Cholesterol. Show all posts
Saturday, January 19, 2008
Monday, January 14, 2008
ENHANCE - Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone
Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE)
Trial Summary
Title:
Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE)
Trial Sponsor: Merck/Schering-PloughYear
Presented: 2008
Description
The following information was derived from a Merck/Schering-Plough press release from January 14, 2008; full data are to be presented at the 2008 ACC Scientific Session.
Hypothesis
The goal of this trial was to compare the mean change in the intima-media thickness (IMT) measured at three sites in the carotid arteries between patients with Heterozygous Familial Hypercholesterolemia (HeFH) treated with ezetimibe/simvastatin 10/80 mg versus patients treated with high-dose simvastatin 80 mg alone over a two-year period.
Principal Findings
A total of 720 patients with HeFH were randomized in this multinational, randomized, double-blind, active comparator trial: 357 to the ezetimibe/simvastatin arm and 363 to the high-dose simvastatin arm. Images were obtained from the right and left carotid arteries at three sites at baseline, 6, 12, 18, and 24 months. The baseline low-density lipoprotein (LDL) cholesterol levels between the two arms were comparable (319 vs. 318 mg/dl; p=non-significant [NS]). Approximately 80% of patients enrolled in the trial had been on statins previously. The baseline mean carotid IMT measurements were similar between the two arms.
There was no statistically significant difference between the two arms with respect to the primary endpoint, the mean change in carotid IMT. The change from baseline for the ezetimibe/simvastatin arm was 0.0111 mm, compared with 0.0058 mm for the high-dose simvastatin arm (p=0.29).There was no difference in the incidence of cardiovascular clinical events: cardiovascular deaths (0.6 vs. 0.3%), non-fatal myocardial infarction (0.8% vs. 0.6%), non-fatal stroke (0.3% vs. 0.3%), and need for revascularization (1.7% vs. 1.4%) [p=NS for all].
There was, however, a significant reduction in LDL lowering noted in the ezetimibe/simvastatin arm compared with the simvastatin arm (58% vs. 41%; p<0.01).The overall incidence of treatment-related adverse events was similar between the two groups: consecutive elevations of serum transaminases ≥ 3X ULN (2.8% vs. 2.2%), elevated CPK ≥ 10 X ULN (1.1% vs. 2.2%), and elevated CPK ≥ 10X ULN with muscle symptoms (0.6% vs. 0.3%) [p=NS for all]. There were no cases of rhabdomyolysis reported in either arm.
Interpretation
The results of the multicenter, randomized ENHANCE trial seem to suggest that in patients with very high baseline LDL levels, such as those with heterozygous familial hypercholesterolemia, the combination of ezetimibe/simvastatin 10/80 mg does not result in significant changes in the mean carotid IMT at 2 years when compared with high-dose simvastatin 80 mg alone. There was also no difference in the incidence of cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, or need for revascularization, although this study was not powered to study clinical outcomes. The LDL-lowering effect of ezetimibe/simvastatin was greater than that achieved with high-dose simvastatin alone.
Although this was a negative study, it will be interesting to see if larger ongoing trials will be able to demonstrate any relative superiority of the combination of ezetimibe/simvastatin in improving cardiovascular outcomes in high-risk patients as compared with simvastatin alone.
Study DesignRandomized. Blinded. Parallel.
Patients Enrolled: 720
Mean Follow-Up: 24 months
Trial Summary
Title:
Effect of Combination Ezetimibe and High-Dose Simvastatin vs. Simvastatin Alone on the Atherosclerotic Process in Patients With Heterozygous Familial Hypercholesterolemia (ENHANCE)
Trial Sponsor: Merck/Schering-PloughYear
Presented: 2008
Description
The following information was derived from a Merck/Schering-Plough press release from January 14, 2008; full data are to be presented at the 2008 ACC Scientific Session.
Hypothesis
The goal of this trial was to compare the mean change in the intima-media thickness (IMT) measured at three sites in the carotid arteries between patients with Heterozygous Familial Hypercholesterolemia (HeFH) treated with ezetimibe/simvastatin 10/80 mg versus patients treated with high-dose simvastatin 80 mg alone over a two-year period.
Principal Findings
A total of 720 patients with HeFH were randomized in this multinational, randomized, double-blind, active comparator trial: 357 to the ezetimibe/simvastatin arm and 363 to the high-dose simvastatin arm. Images were obtained from the right and left carotid arteries at three sites at baseline, 6, 12, 18, and 24 months. The baseline low-density lipoprotein (LDL) cholesterol levels between the two arms were comparable (319 vs. 318 mg/dl; p=non-significant [NS]). Approximately 80% of patients enrolled in the trial had been on statins previously. The baseline mean carotid IMT measurements were similar between the two arms.
There was no statistically significant difference between the two arms with respect to the primary endpoint, the mean change in carotid IMT. The change from baseline for the ezetimibe/simvastatin arm was 0.0111 mm, compared with 0.0058 mm for the high-dose simvastatin arm (p=0.29).There was no difference in the incidence of cardiovascular clinical events: cardiovascular deaths (0.6 vs. 0.3%), non-fatal myocardial infarction (0.8% vs. 0.6%), non-fatal stroke (0.3% vs. 0.3%), and need for revascularization (1.7% vs. 1.4%) [p=NS for all].
There was, however, a significant reduction in LDL lowering noted in the ezetimibe/simvastatin arm compared with the simvastatin arm (58% vs. 41%; p<0.01).The overall incidence of treatment-related adverse events was similar between the two groups: consecutive elevations of serum transaminases ≥ 3X ULN (2.8% vs. 2.2%), elevated CPK ≥ 10 X ULN (1.1% vs. 2.2%), and elevated CPK ≥ 10X ULN with muscle symptoms (0.6% vs. 0.3%) [p=NS for all]. There were no cases of rhabdomyolysis reported in either arm.
Interpretation
The results of the multicenter, randomized ENHANCE trial seem to suggest that in patients with very high baseline LDL levels, such as those with heterozygous familial hypercholesterolemia, the combination of ezetimibe/simvastatin 10/80 mg does not result in significant changes in the mean carotid IMT at 2 years when compared with high-dose simvastatin 80 mg alone. There was also no difference in the incidence of cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, or need for revascularization, although this study was not powered to study clinical outcomes. The LDL-lowering effect of ezetimibe/simvastatin was greater than that achieved with high-dose simvastatin alone.
Although this was a negative study, it will be interesting to see if larger ongoing trials will be able to demonstrate any relative superiority of the combination of ezetimibe/simvastatin in improving cardiovascular outcomes in high-risk patients as compared with simvastatin alone.
Study DesignRandomized. Blinded. Parallel.
Patients Enrolled: 720
Mean Follow-Up: 24 months
Saturday, January 12, 2008
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, November 30, 2007
Cholesterol seen tied to heart disease, not stroke
Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55 000 vascular deaths
The Lancet 2007; 370:1829-1839
Summary
Background
Age, sex, and blood pressure could modify the associations of total cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular mortality. This meta-analysis combined prospective studies of vascular mortality that recorded both blood pressure and total cholesterol at baseline, to determine the joint relevance of these two risk factors.
Methods
Information was obtained from 61 prospective observational studies, mostly in western Europe or North America, consisting of almost 900 000 adults without previous disease and with baseline measurements of total cholesterol and blood pressure. During nearly 12 million person years at risk between the ages of 40 and 89 years, there were more than 55 000 vascular deaths (34 000 ischaemic heart disease [IHD], 12 000 stroke, 10 000 other). Information about HDL cholesterol was available for 150 000 participants, among whom there were 5000 vascular deaths (3000 IHD, 1000 stroke, 1000 other). Reported associations are with usual cholesterol levels (ie, corrected for the regression dilution bias).
Findings
1 mmol/L lower total cholesterol was associated with about a half (hazard ratio 0·44 [95% CI 0·42–0·48]), a third (0·66 [0·65–0·68]), and a sixth (0·83 [0·81–0·85]) lower IHD mortality in both sexes at ages 40–49, 50–69, and 70–89 years, respectively, throughout the main range of cholesterol in most developed countries, with no apparent threshold. The proportional risk reduction decreased with increasing blood pressure, since the absolute effects of cholesterol and blood pressure were approximately additive. Of various simple indices involving HDL cholesterol, the ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40% more informative than non-HDL cholesterol and more than twice as informative as total cholesterol). Total cholesterol was weakly positively related to ischaemic and total stroke mortality in early middle age (40–59 years), but this finding could be largely or wholly accounted for by the association of cholesterol with blood pressure. Moreover, a positive relation was seen only in middle age and only in those with below-average blood pressure; at older ages (70–89 years) and, particularly, for those with systolic blood pressure over about 145 mm Hg, total cholesterol was negatively related to haemorrhagic and total stroke mortality. The results for other vascular mortality were intermediate between those for IHD and stroke.
Interpretation
Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels. The absence of an independent positive association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained, and invites further research. Nevertheless, there is conclusive evidence from randomised trials that statins substantially reduce not only coronary event rates but also total stroke rates in patients with a wide range of ages and blood pressures.
The Lancet 2007; 370:1829-1839
Summary
Background
Age, sex, and blood pressure could modify the associations of total cholesterol (and its main two fractions, HDL and LDL cholesterol) with vascular mortality. This meta-analysis combined prospective studies of vascular mortality that recorded both blood pressure and total cholesterol at baseline, to determine the joint relevance of these two risk factors.
Methods
Information was obtained from 61 prospective observational studies, mostly in western Europe or North America, consisting of almost 900 000 adults without previous disease and with baseline measurements of total cholesterol and blood pressure. During nearly 12 million person years at risk between the ages of 40 and 89 years, there were more than 55 000 vascular deaths (34 000 ischaemic heart disease [IHD], 12 000 stroke, 10 000 other). Information about HDL cholesterol was available for 150 000 participants, among whom there were 5000 vascular deaths (3000 IHD, 1000 stroke, 1000 other). Reported associations are with usual cholesterol levels (ie, corrected for the regression dilution bias).
Findings
1 mmol/L lower total cholesterol was associated with about a half (hazard ratio 0·44 [95% CI 0·42–0·48]), a third (0·66 [0·65–0·68]), and a sixth (0·83 [0·81–0·85]) lower IHD mortality in both sexes at ages 40–49, 50–69, and 70–89 years, respectively, throughout the main range of cholesterol in most developed countries, with no apparent threshold. The proportional risk reduction decreased with increasing blood pressure, since the absolute effects of cholesterol and blood pressure were approximately additive. Of various simple indices involving HDL cholesterol, the ratio total/HDL cholesterol was the strongest predictor of IHD mortality (40% more informative than non-HDL cholesterol and more than twice as informative as total cholesterol). Total cholesterol was weakly positively related to ischaemic and total stroke mortality in early middle age (40–59 years), but this finding could be largely or wholly accounted for by the association of cholesterol with blood pressure. Moreover, a positive relation was seen only in middle age and only in those with below-average blood pressure; at older ages (70–89 years) and, particularly, for those with systolic blood pressure over about 145 mm Hg, total cholesterol was negatively related to haemorrhagic and total stroke mortality. The results for other vascular mortality were intermediate between those for IHD and stroke.
Interpretation
Total cholesterol was positively associated with IHD mortality in both middle and old age and at all blood pressure levels. The absence of an independent positive association of cholesterol with stroke mortality, especially at older ages or higher blood pressures, is unexplained, and invites further research. Nevertheless, there is conclusive evidence from randomised trials that statins substantially reduce not only coronary event rates but also total stroke rates in patients with a wide range of ages and blood pressures.
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.
Monday, October 8, 2007
Adding omega-3 fatty acids to stable statin therapy reduces triglyceride levels, without raising LDL
Adding omega-3 fatty acids to stable statin therapy reduces triglyceride levels, without raising LDL
The Heart.org
New York, NY - The addition of an omega-3 fatty-acid supplement to statin therapy in patients with persistent hypertriglyceridemia significantly reduced triglyceride levels and non-HDL-cholesterol levels, all without a significant increase in LDL-cholesterol levels
Presenting the results of the study at the 16th International Symposium on Drugs Affecting Lipid Metabolism in New York City this weekend, Bays explained that while the Food and Drug Administration has approved the addition of omega-3 fatty-acid supplementation to statin-treated patients with triglyceride levels >500 mg/dL, the addition of the polyunsaturated fatty acid is not currently approved for use in patients with triglyceride levels <500 mg/dL.
Bays acknowledged that the study addresses only the reduction in triglyceride levels and that it is not clear what clinical benefit would arise from further lowering triglycerides in patients with levels between 200 mg/dL and 500 mg/dL.
The Heart.org
New York, NY - The addition of an omega-3 fatty-acid supplement to statin therapy in patients with persistent hypertriglyceridemia significantly reduced triglyceride levels and non-HDL-cholesterol levels, all without a significant increase in LDL-cholesterol levels
Presenting the results of the study at the 16th International Symposium on Drugs Affecting Lipid Metabolism in New York City this weekend, Bays explained that while the Food and Drug Administration has approved the addition of omega-3 fatty-acid supplementation to statin-treated patients with triglyceride levels >500 mg/dL, the addition of the polyunsaturated fatty acid is not currently approved for use in patients with triglyceride levels <500 mg/dL.
Bays acknowledged that the study addresses only the reduction in triglyceride levels and that it is not clear what clinical benefit would arise from further lowering triglycerides in patients with levels between 200 mg/dL and 500 mg/dL.
Thursday, September 27, 2007
HDL Levels Remain Predictive of Heart Risk Even in the Face of Very Low LDL
HDL Levels Remain Predictive of Heart Risk Even in the Face of Very Low LDL
HDL levels retain their prognostic value in patients treated with statins — even among those who achieve very low LDL levels — researchers report in the New England Journal of Medicine.
A post hoc analysis from the industry-funded Treating to New Targets study examined the predictive value of HDL levels on nearly 10,000 adults with coronary heart disease after 3 months of atorvastatin treatment.
After multivariate adjustment, the 5-year risk for major cardiovascular events was reduced by 25% among patients in the highest quintile of HDL cholesterol compared with those in the lowest quintile. Even among patients who had achieved LDL levels below 70 mg/dL, risk remained significantly reduced (by 39%) in the highest HDL quintile.
Writing in Journal Watch General Medicine, Allan S. Brett concludes: "Whether patients with both low LDL and low HDL would benefit from additional drug therapies to raise HDL cholesterol is unclear. "
NEJM article (Free abstract; full text requires subscription)
Related Journal Watch link(s):
Previous Physician's First Watch coverage of Treating to New Targets study (Free)
Journal Watch General Medicine summary (Free)
Journal Watch Cardiology summary (Free)
HDL levels retain their prognostic value in patients treated with statins — even among those who achieve very low LDL levels — researchers report in the New England Journal of Medicine.
A post hoc analysis from the industry-funded Treating to New Targets study examined the predictive value of HDL levels on nearly 10,000 adults with coronary heart disease after 3 months of atorvastatin treatment.
After multivariate adjustment, the 5-year risk for major cardiovascular events was reduced by 25% among patients in the highest quintile of HDL cholesterol compared with those in the lowest quintile. Even among patients who had achieved LDL levels below 70 mg/dL, risk remained significantly reduced (by 39%) in the highest HDL quintile.
Writing in Journal Watch General Medicine, Allan S. Brett concludes: "Whether patients with both low LDL and low HDL would benefit from additional drug therapies to raise HDL cholesterol is unclear. "
NEJM article (Free abstract; full text requires subscription)
Related Journal Watch link(s):
Previous Physician's First Watch coverage of Treating to New Targets study (Free)
Journal Watch General Medicine summary (Free)
Journal Watch Cardiology summary (Free)
Monday, September 17, 2007
Most American Women Don't Know Their Cholesterol Level
Most American Women Don't Know Their Cholesterol Level
Medical News today
17 Sep 2007
80 per cent of women in the US between 18 and 44 don't know their cholesterol level, despite the fact that cholesterol is a major risk factor for the biggest killer of American women, heart disease.
Most women don't understand about cholesterol, concluded a recent survey by the Society for Women's Health Research (SWHR), an advocacy organization based in Washington DC.
President and CEO of the SWHR, Phyllis Greenberger, said:
"Heart disease is a serious threat to women. That fact that only one in five women surveyed knew their cholesterol level shows how much work remains to be done."
"You can't wait until mid-life or later to monitor or manage your cholesterol, which is a major risk factor for heart disease in both women and men," she explained.
A spokeswoman for the American Heart Association, Dr Mary Ann Bauman, who is an internal medicine specialist said:
"For the most part, women do not believe that heart disease risk pertains to them."
"They are often aware of the risk factors, but underestimate their own personal risk," she added.
Bauman suggested the reason was women tended to ignore themselves and focused on looking after others.
She added that despite many public health campaigns, women were still more concerned about other diseases such as breast cancer.
"Most women do not have a fear of heart disease, so it is easy to ignore the risks or warning signs," said Bauman.
Over 50 per cent of the women surveyed aged between 18 and 44 were concerned about cholesterol in general but only one in 5 knew what her personal cholesterol count was. 25 per cent did not even know how cholesterol is tested.
High cholesterol raises the risk of angina, stroke, heart disease and heart attack.
About half of American adults have high cholesterol, according to statistics from the National Heart, Lung, and Blood Institute's (NHLBI) National Cholesterol Education Program.
A person's cholesterol count is made up of three things: low density lipoprotein (LDL or "bad" cholesterol), high density lipoproteins (HDL or "good" cholesterol) and triglycerides, a type of blood fat.
According to the American Heart Association, you should aim for a "desirable" total cholesterol count that is under 200 mg per decilitre or less than 5.2 millimoles per litre.
High LDL increases risk of heart disease and stroke because it promotes deposits of plaque that make blood vessels narrower. An optimum LDL count should be no higher than 100.
Low HDL is linked to increased risk of cardiovascular disease, and an optimum level for women says the SWHR is 50 and above.
Some risk factors for heart disease are controllable and some are uncontrollable, like family history, age and being post menopausal.
Apart from cholesterol, the controllable risk factors for heart disease include: smoking, high blood pressure, obesity, diabetes and a sedentary lifestyle.
Bauman said the good news is there are several ways a woman can control cholesterol and reduce her risk of heart disease:
Take regular exercise.
Maintain a healthy weight.
Eat lots of fruit and vegetables.
Keep to a diet low in saturated fats and cholesterol.
Go for regular health screening, and check cholesterol every 5 years say the AHA and the NHLBI.
Giving up smoking and tobacco also reduces heart disease risk.
People with a family history of heart disease or high cholesterol should probably start regular health screening earlier than the recommended age of 20. Bauman said that lifestyle changes at a young age make a difference later in life:
"I think of heart disease as a disease of adolescence which manifests itself in adulthood," said Bauman.
"We must start early!" she urged.
Click here for Society for Women's Health Research (SWHR).
Medical News today
17 Sep 2007
80 per cent of women in the US between 18 and 44 don't know their cholesterol level, despite the fact that cholesterol is a major risk factor for the biggest killer of American women, heart disease.
Most women don't understand about cholesterol, concluded a recent survey by the Society for Women's Health Research (SWHR), an advocacy organization based in Washington DC.
President and CEO of the SWHR, Phyllis Greenberger, said:
"Heart disease is a serious threat to women. That fact that only one in five women surveyed knew their cholesterol level shows how much work remains to be done."
"You can't wait until mid-life or later to monitor or manage your cholesterol, which is a major risk factor for heart disease in both women and men," she explained.
A spokeswoman for the American Heart Association, Dr Mary Ann Bauman, who is an internal medicine specialist said:
"For the most part, women do not believe that heart disease risk pertains to them."
"They are often aware of the risk factors, but underestimate their own personal risk," she added.
Bauman suggested the reason was women tended to ignore themselves and focused on looking after others.
She added that despite many public health campaigns, women were still more concerned about other diseases such as breast cancer.
"Most women do not have a fear of heart disease, so it is easy to ignore the risks or warning signs," said Bauman.
Over 50 per cent of the women surveyed aged between 18 and 44 were concerned about cholesterol in general but only one in 5 knew what her personal cholesterol count was. 25 per cent did not even know how cholesterol is tested.
High cholesterol raises the risk of angina, stroke, heart disease and heart attack.
About half of American adults have high cholesterol, according to statistics from the National Heart, Lung, and Blood Institute's (NHLBI) National Cholesterol Education Program.
A person's cholesterol count is made up of three things: low density lipoprotein (LDL or "bad" cholesterol), high density lipoproteins (HDL or "good" cholesterol) and triglycerides, a type of blood fat.
According to the American Heart Association, you should aim for a "desirable" total cholesterol count that is under 200 mg per decilitre or less than 5.2 millimoles per litre.
High LDL increases risk of heart disease and stroke because it promotes deposits of plaque that make blood vessels narrower. An optimum LDL count should be no higher than 100.
Low HDL is linked to increased risk of cardiovascular disease, and an optimum level for women says the SWHR is 50 and above.
Some risk factors for heart disease are controllable and some are uncontrollable, like family history, age and being post menopausal.
Apart from cholesterol, the controllable risk factors for heart disease include: smoking, high blood pressure, obesity, diabetes and a sedentary lifestyle.
Bauman said the good news is there are several ways a woman can control cholesterol and reduce her risk of heart disease:
Take regular exercise.
Maintain a healthy weight.
Eat lots of fruit and vegetables.
Keep to a diet low in saturated fats and cholesterol.
Go for regular health screening, and check cholesterol every 5 years say the AHA and the NHLBI.
Giving up smoking and tobacco also reduces heart disease risk.
People with a family history of heart disease or high cholesterol should probably start regular health screening earlier than the recommended age of 20. Bauman said that lifestyle changes at a young age make a difference later in life:
"I think of heart disease as a disease of adolescence which manifests itself in adulthood," said Bauman.
"We must start early!" she urged.
Click here for Society for Women's Health Research (SWHR).
Tuesday, September 11, 2007
Traditional risk factors fail to explain over half of CHD risk in overweight people
Traditional risk factors fail to explain over half of CHD risk in overweight people
11 September 2007
MedWire News: Blood pressure and cholesterol levels explain less than half of the excess risk for coronary heart disease (CHD) in people who are overweight or obese, results of a meta-analysis suggest.
"This implies that, even under the theoretical scenario that optimal treatment would be available against hypertension and hypercholesterolemia in overweight persons, they still would have an elevated risk of CHD," say the researchers.
Writing in the Archives of Internal Medicine, Rik Bogers (National Institute for Public Health and the Environment, Bilthoven, The Netherlands) and colleagues list several mechanisms that could contribute to the increased CHD risk in overweight people.
These include low-grade inflammation, endothelial dysfunction, a tendency toward coagulation, and left ventricular hypertrophy.
"Obviously, overweight is associated with increased risk of Type 2 diabetes mellitus," they add.
The findings emerge from a collaborative meta-analysis involving investigators from 31 prospective cohort studies, including large studies such as the Nurses' Health Study, the Norwegian Counties Study, and the Whitehall Study.
This provided data on 302,296 people who suffered 18,000 CHD events. CHD risk was assessed in relation to body mass index (BMI) categories for 14 cohorts and in relation to BMI as a continuous variable for 21 cohorts.
Overweight people (BMI 25.0-29.9) had a relative risk for CHD of 1.32, compared with normal-weight people, after accounting for age, gender, physical activity, and smoking status.
The corresponding relative risk in obese people (BMI ≥30.0) was 1.81.
Accounting for blood pressure and cholesterol levels reduced the relative risks for CHD to 1.17 and 1.49 for overweight and obese people, respectively, compared with normal-weight people.
Thus, blood pressure and cholesterol levels accounted for 47% and 40% of the excess CHD risk associated with overweight and obesity, respectively.
Each 5-unit increase in BMI increased CHD risk 1.29 fold before accounting for blood pressure and cholesterol levels, and 1.16 fold after allowing for these risk factors.
"Even moderate overweight is associated with increased risk of CHD," the researchers stress.
"Because high blood pressure and cholesterol levels are plausible intermediary factors in the causal pathways linking overweight and CHD, adjusting for them in epidemiological analyses certainly results in underestimating the total public health impact of overweight."
Arch Intern Med 2007; 167: 1720-1728
11 September 2007
MedWire News: Blood pressure and cholesterol levels explain less than half of the excess risk for coronary heart disease (CHD) in people who are overweight or obese, results of a meta-analysis suggest.
"This implies that, even under the theoretical scenario that optimal treatment would be available against hypertension and hypercholesterolemia in overweight persons, they still would have an elevated risk of CHD," say the researchers.
Writing in the Archives of Internal Medicine, Rik Bogers (National Institute for Public Health and the Environment, Bilthoven, The Netherlands) and colleagues list several mechanisms that could contribute to the increased CHD risk in overweight people.
These include low-grade inflammation, endothelial dysfunction, a tendency toward coagulation, and left ventricular hypertrophy.
"Obviously, overweight is associated with increased risk of Type 2 diabetes mellitus," they add.
The findings emerge from a collaborative meta-analysis involving investigators from 31 prospective cohort studies, including large studies such as the Nurses' Health Study, the Norwegian Counties Study, and the Whitehall Study.
This provided data on 302,296 people who suffered 18,000 CHD events. CHD risk was assessed in relation to body mass index (BMI) categories for 14 cohorts and in relation to BMI as a continuous variable for 21 cohorts.
Overweight people (BMI 25.0-29.9) had a relative risk for CHD of 1.32, compared with normal-weight people, after accounting for age, gender, physical activity, and smoking status.
The corresponding relative risk in obese people (BMI ≥30.0) was 1.81.
Accounting for blood pressure and cholesterol levels reduced the relative risks for CHD to 1.17 and 1.49 for overweight and obese people, respectively, compared with normal-weight people.
Thus, blood pressure and cholesterol levels accounted for 47% and 40% of the excess CHD risk associated with overweight and obesity, respectively.
Each 5-unit increase in BMI increased CHD risk 1.29 fold before accounting for blood pressure and cholesterol levels, and 1.16 fold after allowing for these risk factors.
"Even moderate overweight is associated with increased risk of CHD," the researchers stress.
"Because high blood pressure and cholesterol levels are plausible intermediary factors in the causal pathways linking overweight and CHD, adjusting for them in epidemiological analyses certainly results in underestimating the total public health impact of overweight."
Arch Intern Med 2007; 167: 1720-1728
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.
Researchers At Cleveland Clinic Identify Site Of 'Dysfunction' In HDL, Carrier Of Good Cholesterol
Researchers At Cleveland Clinic Identify Site Of 'Dysfunction' In HDL, Carrier Of Good Cholesterol0l
8 Aug 2007
Researchers at Cleveland Clinic have identified the region within high density lipoprotein (HDL), the major carrier of "good" cholesterol, that can become dysfunctional within the artery wall, inhibiting the body's ability to fight cholesterol buildup.
The work of the researchers led by Stanley Hazen, M.D., Ph.D., Head of the Section of Preventive Cardiology and Rehabilitation at Cleveland Clinic appears online Aug. 5 in the journal Nature Structural & Molecular Biology in a paper entitled "The Refined Structure of Nascent HDL Reveals a Key Functional Domain for Particle Maturation and Dysfunction." It builds upon the researchers' previous work which determined that not all HDL helps protect arteries from becoming clogged with fatty deposits.
The findings are important because raising HDL levels represents a major target for new treatment strategies of atherosclerosis, the accumulation of harmful plaque in the arteries, by the pharmaceutical industry. Yet it appears that the function as well as the level of the HDL is important. This may also help explain research earlier this year which found that despite raising the level of HDL (good) cholesterol, the drug torcetrapib did not slow the progression of artery disease.
"In this study we describe a refined molecular model of a nascent HDL molecule that is dramatically improved upon its predecessors," Dr. Hazen said. "With our enhanced detail of the HDL molecule structure we are better able to understand the location and mechanics of dysfunction in HDL.
HDL becomes dysfunctional when a specific region on HDL is modified by myeloperoxidase (MPO), an enzyme present in white blood cells and found in atherosclerotic plaque. This inhibits HDL's ability to mature and effectively carry cholesterol cargo from cells of the artery wall. In their paper, the researchers describe the HDL as having a "solar flare" structure.
Zhiping Wu, Ph.D., a research fellow at Cleveland Clinic is the paper's first author. Valentin Gogonea, Ph.D., an Associate Professor in the Department of Chemistry at Cleveland State University collaborated in the research.
Saturday, July 28, 2007
Air Pollution Link To Clogged Arteries
Air Pollution Link To Clogged Arteries
27 Jul 2007
Should we be watching our exposure to airborne pollution as well as our cholesterol levels?
Research now indicates that air pollution has a role to play in atherosclerosis (artery hardening), which can contribute to heart attacks or strokes.
Findings published in the open access journal, Genome Biology, show how the fats that clog arteries work together with air pollution particles, triggering the genes behind inflammation.
A research team drawn from medical and environmental engineering disciplines at the Universities of California, Los Angeles, investigated the relationship between oxidized phospholipids found in the low density lipoprotein (LDL) particles, the 'bad' fats that clog arteries, and diesel exhaust particles. They exposed cells that line human blood vessels (microvascular endothelial cells) to both exhaust particles and oxidised phospholipids, and measured the effect on genes by using microarray expression profiling. This allowed the identification of gene modules containing a high number of co-expressed genes. These modules appear to be activated by a combination of phospholipids and diesel particles and are linked to vascular inflammation pathways. To confirm these findings, the team exposed mice with high cholesterol levels to the pollutant diesel particles, and saw some of the same gene modules upregulated.
The American Cancer Society has reported a six percent increase in cardiopulmonary deaths for every 10 µg/m3 rise in particulates. Exactly how airborne pollutant particles cause cardiovascular injury is poorly understood. But it is known that these particles are generally coated with a number of chemicals such as organic hydrocarbons, transition metals, sulfates and nitrates. Organic hydrocarbons and transition metals inflame airways by generating reactive oxygen species and oxidative stress when combined with oxidised phospholipids in the arteries. This can lead to vascular inflammation, which can in turn lead to increased lesions in the clogged arteries, potentially giving rise to blood clots that trigger heart attack or stroke. These findings bring us closer to understanding the impact our environment has on our health.
"Air pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells"
Ke Wei Gong, Wei Zhao, Ning Li, Berenice Barajas, Michael Kleinman, Constantinos Sioutas, Steve Horvath, Aldons J Lusis, Andre E Nel and Jesus A Araujo
Genome Biology
http://genomebiology.com/
27 Jul 2007
Should we be watching our exposure to airborne pollution as well as our cholesterol levels?
Research now indicates that air pollution has a role to play in atherosclerosis (artery hardening), which can contribute to heart attacks or strokes.
Findings published in the open access journal, Genome Biology, show how the fats that clog arteries work together with air pollution particles, triggering the genes behind inflammation.
A research team drawn from medical and environmental engineering disciplines at the Universities of California, Los Angeles, investigated the relationship between oxidized phospholipids found in the low density lipoprotein (LDL) particles, the 'bad' fats that clog arteries, and diesel exhaust particles. They exposed cells that line human blood vessels (microvascular endothelial cells) to both exhaust particles and oxidised phospholipids, and measured the effect on genes by using microarray expression profiling. This allowed the identification of gene modules containing a high number of co-expressed genes. These modules appear to be activated by a combination of phospholipids and diesel particles and are linked to vascular inflammation pathways. To confirm these findings, the team exposed mice with high cholesterol levels to the pollutant diesel particles, and saw some of the same gene modules upregulated.
The American Cancer Society has reported a six percent increase in cardiopulmonary deaths for every 10 µg/m3 rise in particulates. Exactly how airborne pollutant particles cause cardiovascular injury is poorly understood. But it is known that these particles are generally coated with a number of chemicals such as organic hydrocarbons, transition metals, sulfates and nitrates. Organic hydrocarbons and transition metals inflame airways by generating reactive oxygen species and oxidative stress when combined with oxidised phospholipids in the arteries. This can lead to vascular inflammation, which can in turn lead to increased lesions in the clogged arteries, potentially giving rise to blood clots that trigger heart attack or stroke. These findings bring us closer to understanding the impact our environment has on our health.
"Air pollutant chemicals and oxidized lipids exhibit genome-wide synergistic effects on endothelial cells"
Ke Wei Gong, Wei Zhao, Ning Li, Berenice Barajas, Michael Kleinman, Constantinos Sioutas, Steve Horvath, Aldons J Lusis, Andre E Nel and Jesus A Araujo
Genome Biology
http://genomebiology.com/
Thursday, July 26, 2007
Low LDL cholesterol levels tentatively linked to cancer risk
Cardiovascular News
Low LDL cholesterol levels tentatively linked to cancer risk
26 July 2007
MedWire News: An explorative analysis has found an association between the risk for cancer and achieved level of low-density lipoprotein (LDL) cholesterol in statin trials.
“This analysis doesn’t implicate the statin in increasing the risk of cancer,” stressed study author Richard Karas (Tufts University School of Medicine, Boston, Massachusetts, USA).
“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 investigators included statin-treated participants from 23 trials in their analysis, giving 309,506 person-years of follow-up.
The magnitude of LDL cholesterol reduction achieved by patients was not associated with cancer risk, or with the patients’ risk for elevated liver enzymes or rhabdomyolysis.
Their results are published in the Journal of the American College of Cardiology. In a related comment, journal editors Anthony DeMaria and Ori Ben-Yehuda (University of California at San Diego, USA) observed that over the past 5 years, “no other manuscript has stimulated such intense scrutiny and discussion.”
The only clear treatment-related effect that the researchers detected was an increasing risk for elevated liver enzymes with rising statin dose.
This rate of elevated liver enzymes rose from about 100 per 100,000 person-years with low statin doses to about 250 per 100,000 person-years with high doses. The absolute and percent LDL cholesterol reductions were not associated with the risk for cancer.
But the team found an inverse relationship between achieved LDL cholesterol levels and the risk for cancer, at an R2 of 0.43. In other words, 43% of the variance in cancer incidence could be accounted for by achieved cholesterol levels, although this was not adjusted for confounders.
In their discussion, Karas et al observe that their findings are consistent with epidemiologic studies showing a link between low cholesterol levels and cancer. But they also note that researchers who previously compiled a review of such studies failed to draw any definitive conclusions, and suggested that the proposed association could be due to confounding.
“One potential explanation is the possibility that low cholesterol levels are simply the effect of the disease rather than the cause, and is present before clinical manifestation of the cancer,” say Karas and team.
In an accompanying editorial, John LaRosa (State University of New York Downstate Medical Center, USA) noted that the link between LDL cholesterol levels and cancer can be further studied without the need for more trials, as many LDL-lowering studies have not published data on cancer.
“Lowering LDL represents an intervention of long duration, and we must continue to be vigilant in ensuring that its benefit clearly outweighs its risk,” he said.
“On the other hand, we must not allow that vigilance to deny the benefits of LDL lowering to those who need it.”
LINK:
Primary source: Journal of the American College of CardiologySource reference: Alsheikh-Ali AA et al. "Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer." J Am Coll Cardiol 2007;50:409-418.
J Am Coll Cardiol 2007; 50: 409–418
Low LDL cholesterol levels tentatively linked to cancer risk
26 July 2007
MedWire News: An explorative analysis has found an association between the risk for cancer and achieved level of low-density lipoprotein (LDL) cholesterol in statin trials.
“This analysis doesn’t implicate the statin in increasing the risk of cancer,” stressed study author Richard Karas (Tufts University School of Medicine, Boston, Massachusetts, USA).
“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 investigators included statin-treated participants from 23 trials in their analysis, giving 309,506 person-years of follow-up.
The magnitude of LDL cholesterol reduction achieved by patients was not associated with cancer risk, or with the patients’ risk for elevated liver enzymes or rhabdomyolysis.
Their results are published in the Journal of the American College of Cardiology. In a related comment, journal editors Anthony DeMaria and Ori Ben-Yehuda (University of California at San Diego, USA) observed that over the past 5 years, “no other manuscript has stimulated such intense scrutiny and discussion.”
The only clear treatment-related effect that the researchers detected was an increasing risk for elevated liver enzymes with rising statin dose.
This rate of elevated liver enzymes rose from about 100 per 100,000 person-years with low statin doses to about 250 per 100,000 person-years with high doses. The absolute and percent LDL cholesterol reductions were not associated with the risk for cancer.
But the team found an inverse relationship between achieved LDL cholesterol levels and the risk for cancer, at an R2 of 0.43. In other words, 43% of the variance in cancer incidence could be accounted for by achieved cholesterol levels, although this was not adjusted for confounders.
In their discussion, Karas et al observe that their findings are consistent with epidemiologic studies showing a link between low cholesterol levels and cancer. But they also note that researchers who previously compiled a review of such studies failed to draw any definitive conclusions, and suggested that the proposed association could be due to confounding.
“One potential explanation is the possibility that low cholesterol levels are simply the effect of the disease rather than the cause, and is present before clinical manifestation of the cancer,” say Karas and team.
In an accompanying editorial, John LaRosa (State University of New York Downstate Medical Center, USA) noted that the link between LDL cholesterol levels and cancer can be further studied without the need for more trials, as many LDL-lowering studies have not published data on cancer.
“Lowering LDL represents an intervention of long duration, and we must continue to be vigilant in ensuring that its benefit clearly outweighs its risk,” he said.
“On the other hand, we must not allow that vigilance to deny the benefits of LDL lowering to those who need it.”
LINK:
Primary source: Journal of the American College of CardiologySource reference: Alsheikh-Ali AA et al. "Effect of the magnitude of lipid lowering on risk of elevated liver enzymes, rhabdomyolysis, and cancer." J Am Coll Cardiol 2007;50:409-418.
J Am Coll Cardiol 2007; 50: 409–418
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, June 19, 2007
Lipitor or simvastatin? - Lipitor is not superior
Pfizer Backtracks on Lipitor’s Edge Over Rival
Posted by Jacob Goldstein
Earlier this year, Pfizer issued a press release trumpeting an analysis that suggested the company’s cholesterol-lowering drug Lipitor helped patients more than simvastatin, a cheaper generic competitor originally sold by Merck as Zocor.
Today Pfizer filed a two-paragraph statement with the SEC explaining that those results were wrong. By the study’s primary measure of cardiovascular risks, patients who took Lipitor didn’t fare significantly better than those who took simvastatin.
That’s quite a rowback by Pfizer, which is fighting in the medical trenches to keep Lipitor sales humming. The March press release by Pfizer quoted a study author as saying the “analysis is important for physicians, employers and formulary directors at managed care companies who are making real-world treatment decisions for patients” because it “further supports the cardiovascular benefits previously seen with Lipitor.” There was no corrective press release issued today.
Generic simvastatin has been stealing market share from Lipitor since it became available last year.
The flawed study analyzed data from about 80,000 members of a managed care organization who had taken either Lipitor or simvastatin. The primary analysis compared the rate of serious cardiovascular problems, such as heart attacks and strokes, in patients who had been taking either drug for at least three months. The study found that, after adjusting for differences in doses of the medicines, the risk of cardiovascular events was 14% lower in patients who took Lipitor.
But according to the SEC filing today, “a subsequent review by the Company” found that the difference was in fact only 10% — not enough to be considered statistically significant, the standard test of scientific validity, Pfizer said.
The mistake was due to a “programming error” and came to light after the manuscript was submitted for publication in a medical journal, Pfizer spokeswoman Vanessa Aristide told the Health Blog this afternoon. Initial results from the study were presented at an American Heart Association epidemiology and prevention conference in March.
A secondary analysis included in the study looked at the difference between patients on Lipitor and simvastatin starting on the first day they took the drugs. That analysis found that Lipitor reduced cardiovascular risk by 26% more than simvastatin. The revised findings issued today said that difference was also lower than originally reported, but at 22% it was still enough to be statistically significant.
Update: We just got Pfizer senior vice president Michael Berelowitz on the phone. He explained that the mistake occurred because the initial analysis incorrectly included some data from 2005. The study was supposed to be limited to data from between 2002 and 2004.
The error was discovered while researchers were re-analyzing the data at the request of an expert who was reviewing the manuscript, which had been submitted for publication in a journal. Berelowitz declined to name the publication.
So is Lipitor superior to simvastatin or not, we asked? “We have clinical trial data and real-world data that are intriguing, and I think it should be followed up on,” said Berelowitz, citing a previous study, called IDEAL, that directly compared the two drugs. But that study also narrowly failed to show that Lipitor was superior to simvastatin in reducing heart attacks and heart-related deaths among patients who have already had heart attacks.
He wouldn’t say whether Pfizer is funding additional head-to-head studies of the two drugs. But he encouraged those who control the preferred-drug lists known as formularies to make the comparison for themselves. “People who make formulary decisions should look at their data and see how it plays out in their world.”
LINK: http://blogs.wsj.com/health/
Posted by Jacob Goldstein
Earlier this year, Pfizer issued a press release trumpeting an analysis that suggested the company’s cholesterol-lowering drug Lipitor helped patients more than simvastatin, a cheaper generic competitor originally sold by Merck as Zocor.
Today Pfizer filed a two-paragraph statement with the SEC explaining that those results were wrong. By the study’s primary measure of cardiovascular risks, patients who took Lipitor didn’t fare significantly better than those who took simvastatin.
That’s quite a rowback by Pfizer, which is fighting in the medical trenches to keep Lipitor sales humming. The March press release by Pfizer quoted a study author as saying the “analysis is important for physicians, employers and formulary directors at managed care companies who are making real-world treatment decisions for patients” because it “further supports the cardiovascular benefits previously seen with Lipitor.” There was no corrective press release issued today.
Generic simvastatin has been stealing market share from Lipitor since it became available last year.
The flawed study analyzed data from about 80,000 members of a managed care organization who had taken either Lipitor or simvastatin. The primary analysis compared the rate of serious cardiovascular problems, such as heart attacks and strokes, in patients who had been taking either drug for at least three months. The study found that, after adjusting for differences in doses of the medicines, the risk of cardiovascular events was 14% lower in patients who took Lipitor.
But according to the SEC filing today, “a subsequent review by the Company” found that the difference was in fact only 10% — not enough to be considered statistically significant, the standard test of scientific validity, Pfizer said.
The mistake was due to a “programming error” and came to light after the manuscript was submitted for publication in a medical journal, Pfizer spokeswoman Vanessa Aristide told the Health Blog this afternoon. Initial results from the study were presented at an American Heart Association epidemiology and prevention conference in March.
A secondary analysis included in the study looked at the difference between patients on Lipitor and simvastatin starting on the first day they took the drugs. That analysis found that Lipitor reduced cardiovascular risk by 26% more than simvastatin. The revised findings issued today said that difference was also lower than originally reported, but at 22% it was still enough to be statistically significant.
Update: We just got Pfizer senior vice president Michael Berelowitz on the phone. He explained that the mistake occurred because the initial analysis incorrectly included some data from 2005. The study was supposed to be limited to data from between 2002 and 2004.
The error was discovered while researchers were re-analyzing the data at the request of an expert who was reviewing the manuscript, which had been submitted for publication in a journal. Berelowitz declined to name the publication.
So is Lipitor superior to simvastatin or not, we asked? “We have clinical trial data and real-world data that are intriguing, and I think it should be followed up on,” said Berelowitz, citing a previous study, called IDEAL, that directly compared the two drugs. But that study also narrowly failed to show that Lipitor was superior to simvastatin in reducing heart attacks and heart-related deaths among patients who have already had heart attacks.
He wouldn’t say whether Pfizer is funding additional head-to-head studies of the two drugs. But he encouraged those who control the preferred-drug lists known as formularies to make the comparison for themselves. “People who make formulary decisions should look at their data and see how it plays out in their world.”
LINK: http://blogs.wsj.com/health/
Sunday, June 10, 2007
Statins added to WHO list of “essential” drugs ??????
Colin Rose said:
Statins added to WHO list of “essential” drugs
June 8th, 2007
Well, it finally happened. The statin peddlers convinced WHO to add statins to the list of essential drugs.
But look at who was behind the initiative, Dr Gotto
Dr. Gotto receives many thousands of dollars from statin peddlers.
Here is a disclosure statement from a recent publication
“Antonio M. Gotto, Jr., MD, DPhil, serves as a consultant forAstraZeneca, Bristol-Myers Squibb, Johnson & Johnson-Merck, KosPharmaceuticals, Kowa, Merck & Co., Inc., Merck-Schering Plough,Novartis, Pfizer Inc, and Reliant Pharmaceuticals.”
Surely this should have been mentioned in the Cornell press release.
Personally, I refuse to take any advice from anyone who receives even one cent from a drug dealer.
I completely agree with Dr Kishore’s statement:
“Increasingly, ‘Western’ high-fat diets, tobacco use and urbanization havehelped make heart disease a bigger killer than ‘The Big Three’—HIV/AIDS,tuberculosis and malaria—combined.”
Indeed, high risk individuals have high risk lifestyles.
But the FIRST thing to do is change the diet and eliminate tobacco BEFORE labeling statins essential drugs. To do otherwise will reduce any incentive to improve lifestyle and make the obesity and diabetes pandemic even worse.
Do you think that the “developing” world is going to be happy with generic simvastatin? Not likely. They are going to start demanding patented Crestor and Vytorin, just like the rich Americans.
Cubans take no statins but live longer than Americans? If statins are not essential in Cuba, why should they be in Africa?
Link: http://panaceia-or-hygeia.com/medicalmyths/?p=12
Statins added to WHO list of “essential” drugs
June 8th, 2007
Well, it finally happened. The statin peddlers convinced WHO to add statins to the list of essential drugs.
But look at who was behind the initiative, Dr Gotto
Dr. Gotto receives many thousands of dollars from statin peddlers.
Here is a disclosure statement from a recent publication
“Antonio M. Gotto, Jr., MD, DPhil, serves as a consultant forAstraZeneca, Bristol-Myers Squibb, Johnson & Johnson-Merck, KosPharmaceuticals, Kowa, Merck & Co., Inc., Merck-Schering Plough,Novartis, Pfizer Inc, and Reliant Pharmaceuticals.”
Surely this should have been mentioned in the Cornell press release.
Personally, I refuse to take any advice from anyone who receives even one cent from a drug dealer.
I completely agree with Dr Kishore’s statement:
“Increasingly, ‘Western’ high-fat diets, tobacco use and urbanization havehelped make heart disease a bigger killer than ‘The Big Three’—HIV/AIDS,tuberculosis and malaria—combined.”
Indeed, high risk individuals have high risk lifestyles.
But the FIRST thing to do is change the diet and eliminate tobacco BEFORE labeling statins essential drugs. To do otherwise will reduce any incentive to improve lifestyle and make the obesity and diabetes pandemic even worse.
Do you think that the “developing” world is going to be happy with generic simvastatin? Not likely. They are going to start demanding patented Crestor and Vytorin, just like the rich Americans.
Cubans take no statins but live longer than Americans? If statins are not essential in Cuba, why should they be in Africa?
Link: http://panaceia-or-hygeia.com/medicalmyths/?p=12
Tuesday, June 5, 2007
Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials
Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials
Thavendiranthan et al have undertaken a study to examine the role of statins in primary prevention of cardiovascular disease (1)
Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. The authors included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model
seven trials with 42,848 patients were included. Note that the analysis also included primary prevention patients from the HPS trial (more than 80% were in secondary prevention) and the patients from the CARDS trial
mean follow-up was 4.3 years
statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = 0.02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively
statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = 0.13)
no significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed
the authors affirm that statin therapy could reduce the absolute risk of coronary events during the next 4.3 years by 0.75% in low-risk patients (NNT= 133), by 1.63% (NNT=61) in moderate-risk patients and by 2.51% (NNT=40) in high-risk patients. They also conclude that it could be cost-effective in patients with an absolute risk over 20% of having a coronary event in the following 10 years. It would not be cost-effective in patients with a risk <10%, and its use would be controversial in the risk-group of 10-20%
the study authors concluded that, in patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality
Reference:
1. Thavendiranathan P et al. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Nov 27;166(21):2307-13.
Thavendiranthan et al have undertaken a study to examine the role of statins in primary prevention of cardiovascular disease (1)
Cochrane Collaboration, and American College of Physicians Journal Club databases were searched for RCTs published between 1966 and June 2005. The authors included RCTs with follow-up of 1 year or longer, more than 100 major CV events, and 80% or more of the population without CV disease. From each trial, demographic data, lipid profile, CV outcomes, mortality, and adverse outcomes were recorded. Summary relative risk (RR) ratios with 95% confidence intervals (CIs) were calculated using a random effects model
seven trials with 42,848 patients were included. Note that the analysis also included primary prevention patients from the HPS trial (more than 80% were in secondary prevention) and the patients from the CARDS trial
mean follow-up was 4.3 years
statin therapy reduced the RR of major coronary events, major cerebrovascular events, and revascularizations by 29.2% (95% CI, 16.7%-39.8%) (P<.001), 14.4% (95% CI, 2.8%-24.6%) (P = 0.02), and 33.8% (95% CI, 19.6%-45.5%) (P<.001), respectively
statins produced a nonsignificant 22.6% RR reduction in coronary heart disease mortality (95% CI, 0.56-1.08) (P = 0.13)
no significant reduction in overall mortality (RR, 0.92 [95% CI, 0.84-1.01]) (P = .09) or increases in cancer or levels of liver enzymes or creatine kinase were observed
the authors affirm that statin therapy could reduce the absolute risk of coronary events during the next 4.3 years by 0.75% in low-risk patients (NNT= 133), by 1.63% (NNT=61) in moderate-risk patients and by 2.51% (NNT=40) in high-risk patients. They also conclude that it could be cost-effective in patients with an absolute risk over 20% of having a coronary event in the following 10 years. It would not be cost-effective in patients with a risk <10%, and its use would be controversial in the risk-group of 10-20%
the study authors concluded that, in patients without CV disease, statin therapy decreases the incidence of major coronary and cerebrovascular events and revascularizations but not coronary heart disease or overall mortality
Reference:
1. Thavendiranathan P et al. Primary prevention of cardiovascular diseases with statin therapy: a meta-analysis of randomized controlled trials. Arch Intern Med. 2006 Nov 27;166(21):2307-13.
Saturday, June 2, 2007
Saturday, May 19, 2007
Statin Therapy Acute Coronary Syndrome: A Systematic Review
Long-Term Benefit of Statin Therapy Initiated during Hospitalization for an Acute Coronary Syndrome: A Systematic Review of Randomized Trials.
American Journal of Cardiovascular Drugs. 7(2):135-141, 2007.
Bavry, Anthony A 1; Mood, Girish R 1; Kumbhani, Dharam J 2; Borek, Peter P 1; Askari, Arman T 1; Bhatt, Deepak L 1
Abstract:
Objective: This study sought to determine if the initiation of statin (HMG-CoA reductase inhibitor) therapy during acute coronary syndromes reduces long-term mortality and other adverse cardiac outcomes.
Background: Initiation of statin therapy during acute coronary syndromes has not been shown to reduce mortality, myocardial infarction or stroke within 4 months of follow-up.
Methods: Clinical trials that randomized patients with acute coronary syndromes to early statin therapy compared with less intensive lipid reduction (placebo/lower-dose statin/usual care), and reported long-term outcomes were included for analysis.
Results: In all, there were seven studies (L-CAD, PTT, FLORIDA, Colivicchi et al., PROVE-IT, ESTABLISH, and A-to-Z) with 9553 patients who started statin therapy within 12 days of hospital presentation. The incidence of all-cause mortality was 3.4% in the statin group versus 4.6% in the less intensive lipid reduction group over a weighted mean follow-up of 22.9 months (relative risk [RR] 0.74; 95% CI 0.61, 0.90; p = 0.003). The number of patients needed to treat to prevent one death was 84 patients. Similarly, the incidence of cardiovascular mortality in the statin versus the less intensive lipid reduction group was 2.4% versus 3.3% (RR 0.74; 95% CI 0.58, 0.93; p = 0.010), unstable angina 4.1% versus 5.0% (RR 0.81; 95% CI 0.68, 0.98; p = 0.027), revascularization 11.2% versus 12.9% (RR 0.86; 95% CI 0.78, 0.96; p = 0.006), stroke 1.1% versus 1.2% (RR 0.90; 95% CI 0.62, 1.30; p = 0.56), and myocardial infarction 6.6% versus 7.0% (RR 0.94; 95% CI 0.81, 1.09; p = 0.41).
Conclusions: The benefit of early initiation of statin therapy during acute coronary syndromes slowly accrues over time so that a survival advantage is seen around 24 months. Relatively few patients need to be treated to prevent one death over this time period. Furthermore, this approach significantly reduces unstable angina and the need for revascularization.
American Journal of Cardiovascular Drugs. 7(2):135-141, 2007.
Bavry, Anthony A 1; Mood, Girish R 1; Kumbhani, Dharam J 2; Borek, Peter P 1; Askari, Arman T 1; Bhatt, Deepak L 1
Abstract:
Objective: This study sought to determine if the initiation of statin (HMG-CoA reductase inhibitor) therapy during acute coronary syndromes reduces long-term mortality and other adverse cardiac outcomes.
Background: Initiation of statin therapy during acute coronary syndromes has not been shown to reduce mortality, myocardial infarction or stroke within 4 months of follow-up.
Methods: Clinical trials that randomized patients with acute coronary syndromes to early statin therapy compared with less intensive lipid reduction (placebo/lower-dose statin/usual care), and reported long-term outcomes were included for analysis.
Results: In all, there were seven studies (L-CAD, PTT, FLORIDA, Colivicchi et al., PROVE-IT, ESTABLISH, and A-to-Z) with 9553 patients who started statin therapy within 12 days of hospital presentation. The incidence of all-cause mortality was 3.4% in the statin group versus 4.6% in the less intensive lipid reduction group over a weighted mean follow-up of 22.9 months (relative risk [RR] 0.74; 95% CI 0.61, 0.90; p = 0.003). The number of patients needed to treat to prevent one death was 84 patients. Similarly, the incidence of cardiovascular mortality in the statin versus the less intensive lipid reduction group was 2.4% versus 3.3% (RR 0.74; 95% CI 0.58, 0.93; p = 0.010), unstable angina 4.1% versus 5.0% (RR 0.81; 95% CI 0.68, 0.98; p = 0.027), revascularization 11.2% versus 12.9% (RR 0.86; 95% CI 0.78, 0.96; p = 0.006), stroke 1.1% versus 1.2% (RR 0.90; 95% CI 0.62, 1.30; p = 0.56), and myocardial infarction 6.6% versus 7.0% (RR 0.94; 95% CI 0.81, 1.09; p = 0.41).
Conclusions: The benefit of early initiation of statin therapy during acute coronary syndromes slowly accrues over time so that a survival advantage is seen around 24 months. Relatively few patients need to be treated to prevent one death over this time period. Furthermore, this approach significantly reduces unstable angina and the need for revascularization.
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