Literature DB >> 9228438

Cholesterol lowering with statin drugs, risk of stroke, and total mortality. An overview of randomized trials.

P R Hebert1, J M Gaziano, K S Chan, C H Hennekens.   

Abstract

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 SYNTHESIS: 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.

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Year:  1997        PMID: 9228438

Source DB:  PubMed          Journal:  JAMA        ISSN: 0098-7484            Impact factor:   56.272


  136 in total

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Review 2.  Geriatric medicine.

Authors:  S E Straus
Journal:  BMJ       Date:  2001-01-13

3.  Cholesterol and strokes. Cholesterol lowering is indicated for strokes due to carotid atheroma.

Authors:  M F Oliver
Journal:  BMJ       Date:  2000-02-19

Review 4.  Prevention of ischaemic stroke.

Authors:  G Gubitz; P Sandercock
Journal:  BMJ       Date:  2000-12-09

5.  Statins: underused by those who would benefit.

Authors:  S B Hulley; D Grady; W S Browner
Journal:  BMJ       Date:  2000-10-21

Review 6.  The relationship between cholesterol and stroke: implications for antihyperlipidaemic therapy in older patients.

Authors:  C Sarti; M Kaarisalo; J Tuomilehto
Journal:  Drugs Aging       Date:  2000-07       Impact factor: 3.923

7.  HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein.

Authors:  E Wang; C N Casciano; R P Clement; W W Johnson
Journal:  Pharm Res       Date:  2001-06       Impact factor: 4.200

8.  Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I.

Authors:  G Martin; H Duez; C Blanquart; V Berezowski; P Poulain; J C Fruchart; J Najib-Fruchart; C Glineur; B Staels
Journal:  J Clin Invest       Date:  2001-06       Impact factor: 14.808

Review 9.  Evidence based cardiology: Prevention of ischaemic stroke.

Authors:  H J Barnett; M Eliasziw; H E Meldrum
Journal:  BMJ       Date:  1999-06-05

Review 10.  New and emerging data from clinical trials of statins.

Authors:  John C LaRosa
Journal:  Curr Atheroscler Rep       Date:  2004-01       Impact factor: 5.113

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