This paper is only available as a PDF. To read, Please Download here.
Abstract
Background: In 2005, the Cholesterol Treatment Trialists' Collaboration (CTTC) quantified the
relationship between reduction in low-density lipoprotein cholesterol (LDL-C) achieved
by statin treatment and reduction in cardiovascular risk. Since this publication,
several large statin trials have been reported.
Objective: The objective of our analysis was to extend the CTTC results by including active-controlled
trials and other trials published since 2005.
Methods: A literature search in English (1966–December 2008) was undertaken of MEDLINE, EMBASE,
Derwent drug file databases, and the Cochrane library using standard MESH terms (cardiovascular disease, death, fatal outcome, pravastatin, simvastatin, atorvastatin,
rosuvastatin, fluvastatin, lovastatin, and hydroxymethylglutaryl coenzyme A reductase inhibitors) to identify randomized trials of statins (placebo controlled, active controlled,
or usual care) that reported clinical outcomes, enrolled >1000 subjects, and followed
them up for ≥1 year. Random effects meta-regression was used to analyze the relationship
between absolute changes in LDL-C and risk for cardiovascular events.
Results: Twenty-five trials were included in a primary analysis involving 155,613 subjects,
6321 vascular deaths, 23,791 major vascular events, 11,357 major coronary events,
and 4717 strokes. For every 25-mg/dL (0.65-mmol/L) reduction in LDL-C, the relative
risk (95% CI) for various cardiovascular outcomes was as follows: vascular mortality,
0.89 (0.87–0.92); major vascular events, 0.86 (0.84–0.88); major coronary events,
0.84 (0.82–0.86); and stroke, 0.90 (0.86–0.94).
Conclusions: Based on meta-regression analysis of these trials, there was a significant positive
relationship between reduction in LDL-C and reduction in the risk for major cardiovascular
events. These results support and extend the findings of the CTTC.
Key words:
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical TherapeuticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian Simvastatin Survival Study (4S).Lancet. 1994; 344: 1383-1389
- MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: A randomised placebo-controlled trial.Lancet. 2002; 360: 7-22
- Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): Multicentre randomised placebo-controlled trial.Lancet. 2004; 364: 685-696
- Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: Systematic review and metaanalysis.BMJ. 2003; 326: 1423
- Efficacy and safety of cholesterol-lowering treatment: Prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins [published corrections appear in Lancet. 2005;366:1358 and Lancet. 2008;371:2084].Lancet. 2005; 366: 1267-1278
- Explaining heterogeneity in metaanalysis: A comparison of methods.Stat Med. 1999; 18: 2693-2708
- Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: Results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.JAMA. 1998; 279: 1615-1622
- Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal Transplant (ALERT) trial.Kidney Int. 2004; 66: 1549-1555
- Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT).JAMA. 2002; 288: 2998-3007
- Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid-lowering disease management clinics: The ALLIANCE study.J Am Coll Cardiol. 2004; 44: 1772-1779
- Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): A multicentre randomised controlled trial.Lancet. 2003; 361: 1149-1158
- Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in subjects with type 2 diabetes: The Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in Non-Insulin-Dependent Diabetes Mellitus (ASPEN).Diabetes Care. 2006; 29: 1478-1485
- Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: Phase Z of the A to Z trial.JAMA. 2004; 292: 1307-1316
- Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol And Recurrent Events (CARE) trial.Ann Intern Med. 1998; 129: 681-689
- Rosuvastatin in older patients with systolic heart failure.N Engl J Med. 2007; 357: 2248-2261
- Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis [published correction appears in N Engl J Med. 2005;353:1640].N Engl J Med. 2005; 353: 238-248
- Results of the low-dose (20 mg) pravastatin GISSI prevenzione trial in 4271 patients with recent myocardial infarction: Do stopped trials contribute to overall knowledge?.Ital Heart J. 2000; 1: 810-820
- Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study.Curr Med Res Opin. 2002; 18: 220-228
- High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: The IDEAL study: A randomized controlled trial [published correction appears in JAMA. 2005;294:3092].JAMA. 2005; 294: 2437-2445
- Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.N Engl J Med. 2008; 359: 2195-2207
- Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels.N Engl J Med. 1998; 339: 1349-1357
- Fluvastatin for prevention of cardiac events following successful first percutaneous coronary intervention: A randomized controlled trial.JAMA. 2002; 288: 2998-3007
- Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): A prospective randomised controlled trial.Lancet. 2006; 368: 1155-1163
- Effect of an aggressive lipid-lowering strategy on progression of atherosclerosis in the left main coronary artery from patients in the post coronary artery bypass graft trial.Circulation. 2001; 104: 2660-2665
- Pravastatin in elderly individuals at risk of vascular disease (PROSPER): A randomised controlled trial.Lancet. 2002; 360: 1623-1630
- Intensive versus moderate lipid lowering with statins after acute coronary syndromes [published correction appears in N Engl J Med. 2006;354:778].N Engl J Med. 2004; 350: 1495-1504
- High-dose atorvastatin after stroke or transient ischemic attack.N Engl J Med. 2006; 355: 549-559
- Treating to New Targets (TNT) Study: Does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit?.Am J Cardiol. 2004; 93: 154-158
- Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia.N Engl J Med. 1995; 333: 1301-1307
- Assessing the quality of reports of randomized clinical trials: Is blinding necessary?.Controlled Clin Trials. 1996; 17: 1-2
Article info
Publication history
Accepted:
November 14,
2008
Identification
Copyright
© 2009 Excerpta Medica Inc. All rights reserved. Published by Elsevier Inc.
