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Cholesterol Lowering With Statin Drugs, Risk Of Stroke, And Total Mortality. An Overview Of Randomized Trials.

P. Hebert
Published 1997 · Medicine

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Objective. —To examine whether cholesterol lowering with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statin drugs) reduces the risks of stroke and total mortality. Data Sources. —We conducted a computerized literature search from 1985 through 1995 to identify all published trials testing statin drugs. The Cholesterol and Recurrent Events (CARE) data were added after the report was published in October 1996. Our search was limited to English-language articles and included published overviews containing relevant individual trials. Trial Selection. —Criteria for inclusion of randomized trials in the overview were (1) statin drugs alone used to reduce lipid levels rather than multifactorial interventions including another type of cholesterol-lowering drug and (2) inclusion of data on deaths and/or strokes. Data Extraction. —Data were extracted by 2 researchers, and only minor discrepancies, which were easily resolved by discussion, occurred. Principal investigators of the trials and their funding agencies were also contacted to secure any relevant data not included in the published reports. Data Ssynthesis. —A total of 16 individual trials including approximately 29 000 subjects treated and followed up an average of 3.3 years were included in the overview. The average reductions in total and low-density lipoprotein cholesterol achieved were large—22% and 30%, respectively. A total of 454 strokes (fatal plus nonfatal) and 1175 deaths occurred. Those assigned to statin drugs experienced significant reductions in risks of stroke of 29% (95% confidence interval [CI], 14%-41%) as well as total mortality of 22% (95% CI, 12%-31%), which was attributable to a significant reduction in cardiovascular disease (CVD) deaths of 28% (95% CI, 16%-37%). There was no evidence of any increased risk in non-CVD mortality (relative risk [RR], 0.93; 95% CI, 0.75-1.14). There was also no significant increase in risk of cancer (RR, 1.03; 95% CI, 0.90-1.17). Conclusion. —This overview of all published randomized trials of statin drugs demonstrates large reductions in cholesterol and clear evidence of benefit on stroke and total mortality. There was, as expected, a large and significant decrease in CVD mortality, but there was no significant evidence for any increases in either non-CVD deaths or cancer incidence.
This paper references
Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program.
K. Yano (1989)
Prescribed use of cholesterol-lowering drugs in the United States, 1978 through 1988.
D. Wysowski (1990)
Lack of effect of lovastatin on restenosis after coronary angioplasty. Lovastatin Restenosis Trial Study Group.
W. Weintraub (1994)
Cholesterol reduction yields clinical benefit. A new look at old data.
A. L. Gould (1995)
Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials.
M. Muldoon (1990)
Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial.
D. Waters (1994)
Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS)
Maas Investigators (1994)
Beta blockade during and after myocardial infarction: an overview of the randomized trials.
S. Yusuf (1985)
Cholesterol Reduction: Weighing the Benefits and Risks
J. Gaziano (1996)
Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients
F. Sacks (1994)
Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B.
G. Brown (1990)
Prevention of restenosis by lovastatin after successful coronary angioplasty.
R. Sahni (1991)
Treatment of osteoporosis with human parathyroid peptide and observations on effect of sodium fluoride.
J. Reeve (1990)
Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. PLAC I investigation.
B. Pitt (1995)
An overview of trials of cholesterol lowering and risk of stroke.
P. Hebert (1995)
HMG-CoA reductase inhibitors for treatment of hypercholesterolemia.
S. Grundy (1988)
Expanded Clinical Evaluation of Lovastatin (EXCEL) study results. I. Efficacy in modifying plasma lipoproteins and adverse event profile in 8245 patients with moderate hypercholesterolemia.
R. Bradford (1991)
Pravastatin, lipids, and atherosclerosis in the carotid arteries: design features of a clinical trial with carotid atherosclerosis outcome.
J. Crouse (1992)
Effect of cholesterol reduction by simvastatin on progression of coronary atherosclerosis: Design, baseline characteristics, and progress of the Multicenter Anti-Atheroma Study (MAAS).
J. M. Dumont (1993)
Pravastatin, Lipids, and Atherosclerosis in the Carotid Arteries (PLAC-II)
J. Crouse (1995)
Cholesterol Reduction and the Risk for Stroke in Men
David C. Atkins (1993)
Expanded clinical evaluation of lovastatin (EXCEL) study: design and patient characteristics of a double-blind, placebo-controlled study in patients with moderate hypercholesterolemia.
R. Bradford (1990)
Expanded Clinical Evaluation of Lovastatin (EXCEL) Study Results: Effect of Patient Characteristics on Lovastatin‐Induced Changes in Plasma Concentrations of Lipids and Lipoproteins
C. Shear (1992)
Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia
J. Shepherd (1995)
By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease?
M. Law (1994)
Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the multiple risk factor intervention trial.
H. Iso (1989)
Cholesterol reduction and its impact on coronary artery disease and total mortality.
I. Holme (1995)
Lipid-lowering interventions in angiographic trials.
J. Rossouw (1995)
Might treatment of hypercholesterolaemia increase non-cardiac mortality?
M. Oliver (1991)
Carcinogenicity of lipid-lowering drugs.
T. Newman (1996)
The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators.
F. Sacks (1996)
Should there be a moratorium on the use of cholesterol lowering drugs?
G. Davey Smith (1992)
Coronary Angiographic Changes with Lovastatin Therapy: The Monitored Atherosclerosis Regression Study (MARS)
D. Blankenhorn (1993)
Reduction in cardiovascular events during pravastatin therapy. Pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program.
R. Byington (1995)
Pravastatin, lipids, and major coronary events.
C. Furberg (1994)
Current status of risk factors for stroke.
P. Wolf (1983)
Cholesterol, diastolic blood pressure and stroke: 13.000 strokes in 450.000 people in 45 prospective cohorts.
D. Kromhout (1995)
Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS).
J. Jukema (1995)
Design features of a controlled clinical trial to assess the effect of an HMG CoA reductase inhibitor on the progression of coronary artery disease. Canadian Coronary Atherosclerosis Intervention Trial Investigators Montreal, Ottawa, and Toronto, Canada.
D. Waters (1993)
The value of lowering cholesterol after myocardial infarction.
J. Rossouw (1990)
Statistical aspects of the analysis of data from retrospective studies of disease.
N. Mantel (1959)
An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence.
I. Holme (1990)
Kuopio Atherosclerosis Prevention Study (KAPS). A population-based primary preventive trial of the effect of LDL lowering on atherosclerotic progression in carotid and femoral arteries.
R. Salonen (1995)
Does lowering cholesterol cause cancer?
J. Dalen (1996)
The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion.
T. Anderson (1995)
Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group.
C. Furberg (1994)
Once‐daily pravastatin in patients with primary hypercholesterolemia: A dose‐response study
P. H. Jones (1991)

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Margaret Perry (2002)
Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions.
R. Collins (2004)
The metabolic syndrome : lifestyle, drugs or both?
A. Cameron (2005)
The role of statins in preventing stroke.
N. Trubelja (2005)
Low-Density Lipoprotein Cholesterol and Coronary Artery Disease
J. Foody (2006)
Pharmacotherapy for patients undergoing carotid stenting.
D. Gopalan (2006)
Statin therapy in stroke prevention: a meta-analysis involving 121,000 patients.
Christopher P. O'regan (2008)
Long-Term Changes in Weight and Plasma Lipids during Maintenance Treatment with Ziprasidone
P. Weiden (2008)
Effect of T'ai chi chuan training on cardiovascular risk factors in dyslipidemic patients.
C. Lan (2008)
The death rates of smokers and their external effects
John Douglas Fordyce Skatun (2010)
Statin–macrolide interaction risk: a population-based study throughout a general practice database
N. Piacentini (2005)
Clinical Outcomes in Statin Treatment Trials
S. Ross (2016)
Platelet inhibition beyond conventional antiplatelet agents: expanding role of angiotensin receptor blockers, statins and selective serotonin reuptake inhibitors
A. Malinin (2006)
Health Promoting Medications in Older People
Jacinta M Guthridge (1999)
The incidence and aetiology of stroke in the Caerphilly and Speedwell Collaborative Studies II: risk factors for ischaemic stroke.
P. Mccarron (2001)
Use of lipid-lowering drugs during 1991-98 in Northern Jutland, Denmark.
S. Riahi (2001)
Statins in the Primary Prevention of Atherosclerosis-Related Events
B. M. Singh (2004)
Inflammation is a crucial feature of atherosclerosis and a potential target to reduce cardiovascular events.
F. Mach (2005)
Plasma exchange in severe hypertriglyceridemia a clinical study.
G. Kadıkoylu (2006)
Psychiatric Adverse Reactions with Statins, Fibrates and Ezetimibe
M. Tatley (2007)
Are soy foods protective against ischemic stroke
W. Liang (2007)
Effect of an estrogen/statin combination on biochemical markers of endothelial function in human coronary artery cell cultures
A. Mueck (2001)
Inverse association of dietary fat with development of ischemic stroke in men.
M. Gillman (1997)
Lack of mutual pharmacokinetic interaction between cerivastatin, a new HMG-CoA reductase inhibitor, and digoxin in healthy normocholesterolemic volunteers.
P. Weber (1999)
Screening for cardiovascular disease. Concepts, conflicts, and consensus.
J. Frolkis (1999)
Is cholesterol a risk factor for stroke?: No.
W. Landau (1999)
Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype.
P. Meroni (2001)
Lowering lipids after a stroke or transient ischaemic attack.
H. McNaughton (2002)
Ataque isquémico transitorio
M. Eimil (2003)
New perspectives on the pharmacotherapy of ischemic stroke.
J. C. Bradberry (2004)
O uso de estatinas no Acidente Vascular Cerebral
José Olímpio Tavares de Souza (2001)
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