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Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Open accessAbstract
BACKGROUND: Lipid-lowering therapy with statins reduces the risk of cardiovascular events, but the optimal level of low-density lipoprotein (LDL) cholesterol is unclear. METHODS: We enrolled 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days and compared 40 mg of pravastatin daily (standard therapy) with 80 mg of atorvastatin daily (intensive therapy). The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke. The study was designed to establish the noninferiority of pravastatin as compared with atorvastatin with respect to the time to an end-point event. Follow-up lasted 18 to 36 months (mean, 24). RESULTS: The median LDL cholesterol level achieved during treatment was 95 mg per deciliter (2.46 mmol per liter) in the standard-dose pravastatin group and 62 mg per deciliter (1.60 mmol per liter) in the high-dose atorvastatin group (P<0.001). Kaplan-Meier estimates of the rates of the primary end point at two years were 26.3 percent in the pravastatin group and 22.4 percent in the atorvastatin group, reflecting a 16 percent reduction in the hazard ratio in favor of atorvastatin (P=0.005; 95 percent confidence interval, 5 to 26 percent). The study did not meet the prespecified criterion for equivalence but did identify the superiority of the more intensive regimen. CONCLUSIONS: Among patients who have recently had an acute coronary syndrome, an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL cholesterol to levels substantially below current target levels.
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“Likewise, in the PROVE-IT TIMI 22 trial, intensive lipid-lowering with atorvastatin 80 mg reduced LDL-C by 51% and triglycerides by 20%, compared with 22% and 11% reductions with pravastatin (40 mg/day) and was associated with greater protection against death or major cardiovascular events [72].”
From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [72]
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“Likewise, in the PROVE-IT TIMI 22 trial, intensive lipid-lowering with atorvastatin 80 mg reduced LDL-C by 51% and triglycerides by 20%, compared with 22% and 11% reductions with pravastatin (40 mg/day) and was associated with greater protection against death or major cardiovascular events [72].”
From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [72]
In the citing paper
“Lipid profile has long been considered among the most important risk factors for CVD in T2DM, and several trials have confirmed that lowering low-density lipoprotein cholesterol (LDL-C) via statins in T2DM was effective in reducing the risk of CVD [81, 82].”
From Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007–2017 (2018) · cites this paper as [81]
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“In addition to their initial events, such patients are at substantial risk for recurrent, potentially fatal events.”
From Effects of Icosapent Ethyl on Total Ischemic Events (2019) · cites this paper as [7]
In the citing paper
“Because cardiovascular event rates are increased in people with diabetes and established ASCVD, intensive therapy is indicated and has been shown to be of bene fi t in multiple large meta-analyses and randomized cardiovascular outcomes trials (91,99,105,107,108).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [107]
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“These recommendations are based on the observation that high-intensity versus moderate-intensity statin therapy reduces cardiovascular event rates in high-risk individuals with established cardiovascular disease in randomized trials (95,107).”
From 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes—2023 (2023) · cites this paper as [107]
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“In the PACIFIC study740), which was a multicenter observational registry study on ACS, the incidence rate of fatal and nonfatal myocardial infarction was high, at 35/1,000 person-years, despite approximatively 80% subjects being administered statins.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [740]
In the citing paper
“The results of these studies have found that, compared to patients with normal renal function, the risk for cardiovascular events, including cerebrovascular disease, cardiac death, and total mortality increases by 2–3-fold in those with CKD even when the CKD is mild.”
From Japan Atherosclerosis Society (JAS) guidelines for prevention of atherosclerotic cardiovascular diseases 2017 (2018) · cites this paper as [740]
In the citing paper
“Recent clinical trials in high-risk patients, such as those with acute coronary syndromes or previous cardiovascular events (200–202), have demonstrated that more aggressive therapy with high doses of statins to achieve an LDL cholesterol of <70 mg/dl led to a significant reduction in further events.”
From Standards of Medical Care in Diabetes—2009 (2009) · cites this paper as [200]
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Metadata
- Authors
- 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.
- Affiliations
- Brigham and Women's Hospital (US)
- University of Pennsylvania (US)
- Université de Montréal (CA)
- Bristol-Myers Squibb (United States) (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2004-04-08
- Volume
- 350
- Issue
- 15
- Pages
- 1495-1504
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2159449551
- Cited by
- 4,938
- References
- 32
- Citations by year
- 2026: 87 · 2025: 84 · 2024: 121 · 2023: 117 · 2022: 120 · 2021: 129 · 2020: 147 · 2019: 163 · 2018: 155 · 2017: 215 · 2016: 178 · 2015: 216 · 2014: 213 · 2013: 215 · 2012: 229
- FWCI
- 442.24
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- 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
- acute coronary syndrome, statins, intensive lipid-lowering therapy, LDL cholesterol, pravastatin, atorvastatin, non-inferiority, major adverse cardiovascular events, revascularization, myocardial infarction, stroke, unstable angina
- MeSH terms
- Atorvastatin, Angina, Unstable, Anticholesteremic Agents, Cardiovascular Diseases, Female, Heptanoic Acids, Humans, Cholesterol, HDL, Cholesterol, LDL, Male, Middle Aged, Myocardial Infarction, Pyrroles, Proportional Hazards Models, Pravastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors
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