The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Meta-Analysis of Cardiovascular Outcomes Trials Comparing Intensive Versus Moderate Statin Therapy
Open accessAbstract
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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In the citing paper
“Such small changes in LDL-C levels do not seem to affect cardiovascular outcomes and serum lipid profiles with statin administration, which can reduce the LDL-C level by approximately 50 mg/dL (40).”
From Saturated Fat Restriction for Cardiovascular Disease Prevention: A Systematic Review and Meta-analysis of Randomized Controlled Trials (2025) · cites this paper as [40]
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In the citing paper
“Such small changes in LDL-C levels do not seem to affect cardiovascular outcomes and serum lipid profiles with statin administration, which can reduce the LDL-C level by approximately 50 mg/dL (40).”
From Saturated Fat Restriction for Cardiovascular Disease Prevention: A Systematic Review and Meta-analysis of Randomized Controlled Trials (2025) · cites this paper as [40]
Experimental — accuracy not yet measuredIn the citing paper
“Importantly, DM confers excess mortality risk following ACS despite modern therapies”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [409]
In the citing paper
“No increases in new-incidence cancer or non-CVD deaths were observed, which reconfirms the safety of long-term LDL-C-lowering therapy using statins.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [629]
In the citing paper
“The long-term follow-up of large clinical trials of statins that were conducted in the 1990s, such as the West of Scotland Coronary Prevention Study (WOSCOPS) and the Heart Protection Study (HPS)628, 629) confirmed that early initiation of LDLC-lowering therapy regardless of the plasma LDL-C level was useful for the long-term prevention of cardiovascular events and all-cause mortality in high-risk”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [629]
In the citing paper
“Large clinical trials investigating the effects of intensive LDL lowering with statins have demonstrated a substantial benefit over standard-dose statin therapy for preventing non-fatal cardiovascular events74.”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [74]
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Cites
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944
Expert Panel on Detection, E. (2001) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.285.19.2486 · Cited by 26,011
Collaboration, A. T. (2002) · BMJ · doi:10.1136/bmj.324.7329.71 · Cited by 6,943
Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Circulation · doi:10.1161/01.cir.0000133317.49796.0e · Cited by 6,902
Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Cannon, C. P., Braunwald, E., McCabe, C. H., Rader, D. J., Rouleau, J. L., Belder, R., Joyal, S. V., Hill, K. A., Pfeffer, M. A., & Skene, A. M. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040583 · Cited by 4,938
Self-citationSever, P., Dahlöf, B., Poulter, N. R., Wedel, H., Beevers, G., Caulfield, M. J., Collins, R., Kjeldsen, S. E., Kristinsson, A., McInnes, G. T., et al. (2003) · The Lancet · doi:10.1016/s0140-6736(03)12948-0 · Cited by 3,790
Colhoun, H. M., Betteridge, D. J., Durrington, P. N., Hitman, G. A., W Neil, H. A., Livingstone, S. J., Thomason, M. J., Mackness, M. I., Charlton-Menys, V., & Fuller, J. H. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16895-5 · Cited by 3,755
Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease
LaRosa, J. C., Grundy, S. M., Waters, D. D., Shear, C., Barter, P., Fruchart, J.-C., Gotto, A. M., Greten, H., Kastelein, J. J. P., Shepherd, J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050461 · Cited by 3,489
Shepherd, J., Blauw, G. J., Murphy, M. B., Bollen, E. L., Buckley, B. M., Cobbe, S. M., Ford, I., Gaw, A., Hyland, M., Jukema, J. W., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)11600-x · Cited by 3,378
Diener, H.-C., Bogousslavsky, J., Brass, L. M., Cimminiello, C., Csiba, L., Kaste, M., Leys, D., Matias-Guiu, J., & Rupprecht, H.-J. (2004) · The Lancet · doi:10.1016/s0140-6736(04)16721-4 · Cited by 2,275
Effect of Statin Therapy on C-Reactive Protein Levels
Albert, M. A., Danielson, E., Rifai, N., Ridker, P. M., & for the PRINCE Investigators (2001) · JAMA · doi:10.1001/jama.286.1.64 · Cited by 1,644
Pedersen, T. R. (2005) · JAMA · doi:10.1001/jama.294.19.2437 · Cited by 1,548
de Lemos, J. A., Blazing, M. A., Wiviott, S. D., Lewis, E. F., Fox, K. A. A., White, H. D., Rouleau, J.-L., Pedersen, T. R., Gardner, L. H., Mukherjee, R., et al. (2004) · JAMA · doi:10.1001/jama.292.11.1307 · Cited by 1,333
The way I see it: House officers need formal career development
Connor, A. (2002) · BMJ · doi:10.1136/bmj.324.7336.s71 · Cited by 1,138
Mortality Risk Reduction Associated With Smoking Cessation in Patients With Coronary Heart Disease
Critchley, J., & Capewell, S. (2003) · JAMA · doi:10.1001/jama.290.1.86 · Cited by 1,086
Trends in Serum Lipids and Lipoproteins of Adults, 1960-2002
Carroll, M. D. (2005) · JAMA · doi:10.1001/jama.294.14.1773 · Cited by 533
Sever, P., Dahl??f, B., Poulter, N. R., Wedel, H., Beevers, G., Caulfield, M. J., Collins, R., Kjeldsen, S. E., Kristinsson, A., McInnes, G. T., et al. (2004) · Drugs · doi:10.2165/00003495-200464002-00005 · Cited by 525
Use of Lipid-Lowering Medications at Discharge in Patients With Acute Myocardial Infarction
Fonarow, G. C., French, W. J., Parsons, L. S., Sun, H., & Malmgren, J. A. (2001) · Circulation · doi:10.1161/01.cir.103.1.38 · Cited by 227
Intensive Statin Therapy — A Sea Change in Cardiovascular Prevention
Topol, E. J. (2004) · New England Journal of Medicine · doi:10.1056/nejme048061 · Cited by 196
Wiviott, S. D., de Lemos, J. A., Cannon, C. P., Blazing, M. A., Murphy, S. A., McCabe, C. H., Califf, R. M., & Braunwald, E. (2006) · Circulation · doi:10.1161/circulationaha.105.586347 · Cited by 97
Self-citationde Lemos, J. A., Blazing, M. A., & Wiviott, S. D. (2004) · ACC Current Journal Review · doi:10.1016/j.accreview.2004.10.005 · Cited by 79
Mortality Risk Reduction Associated With Smoking Cessation in Patients With Coronary Heart Disease
Critchley, J., & Capewell, S. (2007) · Cited by 50
Pitt, B. (2005) · New England Journal of Medicine · doi:10.1056/nejme058052 · Cited by 47
Efficacy and safety of cholesterol-lowering treatment
Abraha, I., Bonacini, I., & Montedori, A. (2006) · The Lancet · doi:10.1016/s0140-6736(06)68169-5 · Cited by 38
Austin, P. C., & Mamdani, M. (2005) · Circulation · doi:10.1161/circulationaha.104.531582 · Cited by 32
Are Statins Being Underdosed in Clinical Practice?
Steinberg, B. A., Braganza, A. J. M., Eminowicz, G., DiBattiste, P. M., Flaker, G. C., Murphy, S. A., & Cannon, C. P. (2005) · Critical Pathways in Cardiology A Journal of Evidence-Based Medicine · doi:10.1097/01.hpc.0000188384.64039.8f · Cited by 8
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Steinberg, 2006, Statin use and low-density lipoprotein cholesterol goals in 2004, J Am Coll Cardiol, 47, 209A
Cited by
Sorted by citations
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961
Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
Ridker, P. M., Danielson, E., Fonseca, F. A. H., Genest, J., Gotto, A. M., Kastelein, J. J. P., Koenig, W., Libby, P., Lorenzatti, A. J., MacFadyen, J. G., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0807646 · Cited by 6,674
Cholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854
Cosentino, F., Grant, P. J., Aboyans, V., Bailey, C. J., Ceriello, A., Delgado, V., Federici, M., Filippatos, G., Grobbee, D. E., Hansen, T. B., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz486 · Cited by 4,763
Metadata
- Authors
- Cannon, C. P., Steinberg, B. A., Murphy, S. A., Mega, J. L., & Braunwald, E.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Cannon, Christopher P.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 48
- Issue
- 3
- Pages
- 438-445
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2040462758
- Cited by
- 770
- References
- 27
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 20 · 2023: 24 · 2022: 22 · 2021: 23 · 2020: 36 · 2019: 26 · 2018: 30 · 2017: 36 · 2016: 35 · 2015: 28 · 2014: 43 · 2013: 46 · 2012: 48
- FWCI
- 12.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- high-intensity statin therapy, intensive lipid lowering, statin therapy, cardiovascular outcomes, coronary artery disease, acute coronary syndrome, myocardial infarction, coronary death, cardiovascular mortality, TNT trial, IDEAL trial, PROVE IT-TIMI 22, pravastatin, atorvastatin
- MeSH terms
- Cardiovascular Diseases, Coronary Disease, Dose-Response Relationship, Drug, Humans, Syndrome, Randomized Controlled Trials as Topic, Treatment Outcome, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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