Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes

Cannon, Christopher P.; Braunwald, Eugene; McCabe, Carolyn H.; Rader, Daniel J.; Rouleau, Jean L.; Belder, Rene; Joyal, Steven V.; Hill, Karen A.; Pfeffer, Marc A.; Skene, Allan M.

doi:10.1056/nejmoa040583

Cited by 4,938Lipoproteins and Cardiovascular HealthAcute Myocardial Infarction ResearchCancer, Lipids, and Metabolism

Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes

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Cannon, Christopher P., Braunwald, Eugene, McCabe, Carolyn H., Rader, Daniel J., Rouleau, Jean L., Belder, Rene, Joyal, Steven V., Hill, Karen A. +2 more·2004·New England Journal of Medicine

DOI 10.1056/nejmoa040583

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Abstract

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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In the PROVE-IT TIMI 22 trial, atorvastatin 80 mg reduced LDL-C by 51% and TG by 20%, compared with pravastatin 40 mg reductions of 22% and 11%.
“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]
The statistical-analysis passage reports 51% and 22% LDL-C reductions at 30 days, but only among patients who had not previously received statins; the citing sentence omits that qualification. The primary-end-point passage supports greater protection against death or a major cardiovascular event with atorvastatin. Our copy gives baseline triglyceride levels but does not report the claimed 20% and 11% triglyceride reductions. (LLM, conf=0.89)
Experimental — accuracy not yet measured
In PROVE-IT TIMI 22, intensive lipid-lowering with atorvastatin 80 mg was associated with greater protection against death or major cardiovascular events compared with pravastatin.
“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]
Lowering low-density lipoprotein cholesterol via statins in type 2 diabetes is effective in reducing the risk of cardiovascular disease.
“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]
Patients with elevated triglycerides, atherosclerosis, or diabetes receiving statins are at substantial risk for recurrent, potentially fatal ischemic events.
“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]
Cardiovascular event rates are increased in people with diabetes and established ASCVD, and intensive therapy has been shown to be of benefit in multiple large meta-analyses and randomized cardiovascular outcomes trials.
“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]

High-intensity versus moderate-intensity statin therapy reduces cardiovascular event rates in high-risk individuals with established cardiovascular disease in randomized trials.
“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]
In the PACIFIC study, the incidence rate of fatal and nonfatal myocardial infarction was high at 35 per 1,000 person-years despite approximately 80% of subjects being administered statins.
“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]
Compared with 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 chronic kidney disease even when the chronic kidney disease is mild.
“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]
Recent clinical trials in high-risk patients 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.
“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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Self-citation

Effect of pravastatin and atorvastatin on serum C-reactive protein in patients with unstable angina
Jin-zhi, Z. (2006) · Xinxueguan kangfu yixue zazhi
Effect of atorvastatin and pravastatin on serum C-reactive protein
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Atorvastatin is more effective than pravastatin in preventing recurrent cardiac events
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Efficacy and safety of atorvastatin compared to pravastatin in patients with hypercholesterolemia.
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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)
ORCID: Cannon, Christopher P.
Rader, Daniel J.
Rouleau, Jean L.
Pfeffer, Marc A.
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
DOI: 10.1056/nejmoa040583
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 › Surgery › 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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Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes

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