CLINICAL RESEARCH: CORONARY ARTERY DISEASE
Meta-Analysis of Cardiovascular Outcomes Trials Comparing Intensive Versus Moderate Statin Therapy
Christopher P. Cannon, MD*,
Benjamin A. Steinberg, BA,
Sabina A. Murphy, MPH,
Jessica L. Mega, MD and
Eugene Braunwald, MD
Thrombolysis In Myocardial Infarction Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts.
Manuscript received January 23, 2006;
revised manuscript received March 30, 2006,
accepted April 4, 2006.
* Reprint requests and correspondence: Dr. Christopher P. Cannon, TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115. (Email: cpcannon{at}partners.org).
OBJECTIVES: The purpose of this study was to conduct a meta-analysis that compares the reduction of cardiovascular outcomes with high-dose statin therapy versus standard dosing.
BACKGROUND: Debate exists regarding the merit of more intensive lipid lowering with high-dose statin therapy as compared with standard-dose therapy.
METHODS: We searched PubMed and article references for randomized controlled trials of intensive versus standard-dose statin therapy enrolling more than 1,000 patients with either stable coronary heart disease or acute coronary syndromes. Four trials were identified: the TNT (Treating to New Targets) and the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid-Lowering) trials involved patients with stable cardiovascular disease, and the PROVE IT–TIMI-22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction-22) and A-to-Z (Aggrastat-to-Zocor) trials involved patients with acute coronary syndromes. We carried out a meta-analysis of the relative odds on the basis of a fixed-effects model using the Mantel-Haenszel method for the major outcomes of death and cardiovascular events.
RESULTS: A total of 27,548 patients were enrolled in the 4 large trials. The combined analysis yielded a significant 16% odds reduction in coronary death or myocardial infarction (p < 0.00001), as well as a significant 16% odds reduction of coronary death or any cardiovascular event (p < 0.00001). No difference was observed in total or non-cardiovascular mortality, but a trend toward decreased cardiovascular mortality (odds reduction 12%, p = 0.054) was observed.
CONCLUSIONS: Intensive lipid lowering with high-dose statin therapy provides a significant benefit over standard-dose therapy for preventing predominantly non-fatal cardiovascular events.
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Abbreviations and Acronyms
| | A-to-Z = Aggrastat-to-Zocor trial | | ACS = acute coronary syndrome | | CI = confidence interval | | CTT = Cholesterol Treatment Trialists | | IDEAL = Incremental Decrease in End Points Through Aggressive Lipid-Lowering trial | | LDL = low-density lipoprotein | | MI = myocardial infarction | | NCEP = National Cholesterol Education Program | | OR = odds ratio | | PROVE IT–TIMI-22 = Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis In Myocardial Infarction-22 trial | | TNT = Treating to New Targets trial |
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The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study: Evaluation Using Ultrasmall Superparamagnetic Iron Oxide-Enhanced Magnetic Resonance Imaging in Carotid Disease
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E. J. Schaefer, J. A. Gleason, and M. L. Dansinger
Dietary Fructose and Glucose Differentially Affect Lipid and Glucose Homeostasis
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J. M. Tobis and A. Perlowski
Atheroma Volume by Intravascular Ultrasound as a Surrogate for Clinical End Points
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Heart Protection Study Collaborative Group
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[Abstract]
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D. A. Alter, P. I. Oh, and A. Chong
Relationship between cardiac rehabilitation and survival after acute cardiac hospitalization within a universal health care system
European Journal of Cardiovascular Prevention & Rehabilitation,
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J. G. Robinson, S. Wang, B. J. Smith, and T. A. Jacobson
Meta-Analysis of the Relationship Between Non-High-Density Lipoprotein Cholesterol Reduction and Coronary Heart Disease Risk
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R. R. Giraldez, R. P. Giugliano, S. Mohanavelu, S. A. Murphy, C. H. McCabe, C. P. Cannon, and E. Braunwald
Baseline Low-Density Lipoprotein Cholesterol Is an Important Predictor of the Benefit of Intensive Lipid-Lowering Therapy: A PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) Analysis
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M. Y. Chan, K. W. Mahaffey, L. J. Sun, K. S. Pieper, H. D. White, P. E. Aylward, J. J. Ferguson, R. M. Califf, and M. T. Roe
Prevalence, Predictors, and Impact of Conservative Medical Management for Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Who Have Angiographically Documented Significant Coronary Disease
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A. Barnett, G. Hitman, E. Hughes, and K. Khunti
New Perspectives on the Management of Type 2 Diabetes: Report of symposia at the Royal College of Physicians, London, 16 April 2008 and Hilton Hotel, Coventry, 14 May 2008
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J Armitage
Commentary on NICE technology appraisal guidance on ezetimibe for the treatment of primary (heterozygous-familial and non-familial) hypercholesterolaemia
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E. D. Peterson and T. Y. Wang
The Great Debate of 2008--How Low to Go in Preventive Cardiology?
JAMA,
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K. Josan MD, S. R. Majumdar MD MPH, and F. A. McAlister MD MSc
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S. M. Grundy
Promise of Low-Density Lipoprotein-Lowering Therapy for Primary and Secondary Prevention
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A. S. Wierzbicki
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D. G Hackam
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A. Behfar and A. Terzic
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ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) Developed in Collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine
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N. J. Leeper, R. Ardehali, E. M. deGoma, and P. A. Heidenreich
Statin Use in Patients With Extremely Low Low-Density Lipoprotein Levels Is Associated With Improved Survival
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J. Afilalo, A. A Majdan, and M. J Eisenberg
Intensive statin therapy in acute coronary syndromes and stable coronary heart disease: a comparative meta-analysis of randomised controlled trials
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P. Kaul
Cost-effectiveness of high-dose atorvastatin compared with usual-dose simvastatin: less than IDEAL?
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R. E Anderson, K. Brismar, and T. Ivert
Only a minority of patients referred for elective coronary artery bypass surgery have risk factors diagnosed and treated according to established guidelines
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D. G. Hackam and J. D. Spence
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A. Garg and V. Simha
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J. Sanz, P. R. Moreno, and V. Fuster
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N. V. Deshpande, H. M. Mardikar, and D. Deo
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C. P. Cannon and E. Braunwald
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