Intensive lipid lowering with atorvastatin in patients with stable coronary disease

John C. LaRosa, Scott M Grundy, David D. Waters, Charles Shear, Philip Barter, Jean Charles Fruchart, Antonio M. Gotto, Heiner Greten, John J P Kastelein, James Shepherd, Nanette K. Wenger

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). METHODS: A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. RESULTS: The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. CONCLUSIONS: Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.

Original languageEnglish (US)
Pages (from-to)1425-1435
Number of pages11
JournalNew England Journal of Medicine
Volume352
Issue number14
DOIs
StatePublished - Apr 7 2005

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Coronary Disease
Lipids
LDL Cholesterol
Transaminases
Therapeutics
Atorvastatin Calcium
Incidence
Acute Coronary Syndrome
Heart Arrest
Resuscitation
Stroke
Odds Ratio
Myocardial Infarction
Confidence Intervals
Safety
Mortality
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

LaRosa, J. C., Grundy, S. M., Waters, D. D., Shear, C., Barter, P., Fruchart, J. C., ... Wenger, N. K. (2005). Intensive lipid lowering with atorvastatin in patients with stable coronary disease. New England Journal of Medicine, 352(14), 1425-1435. https://doi.org/10.1056/NEJMoa050461

Intensive lipid lowering with atorvastatin in patients with stable coronary disease. / LaRosa, John C.; Grundy, Scott M; Waters, David D.; Shear, Charles; Barter, Philip; Fruchart, Jean Charles; Gotto, Antonio M.; Greten, Heiner; Kastelein, John J P; Shepherd, James; Wenger, Nanette K.

In: New England Journal of Medicine, Vol. 352, No. 14, 07.04.2005, p. 1425-1435.

Research output: Contribution to journalArticle

LaRosa, JC, Grundy, SM, Waters, DD, Shear, C, Barter, P, Fruchart, JC, Gotto, AM, Greten, H, Kastelein, JJP, Shepherd, J & Wenger, NK 2005, 'Intensive lipid lowering with atorvastatin in patients with stable coronary disease', New England Journal of Medicine, vol. 352, no. 14, pp. 1425-1435. https://doi.org/10.1056/NEJMoa050461
LaRosa, John C. ; Grundy, Scott M ; Waters, David D. ; Shear, Charles ; Barter, Philip ; Fruchart, Jean Charles ; Gotto, Antonio M. ; Greten, Heiner ; Kastelein, John J P ; Shepherd, James ; Wenger, Nanette K. / Intensive lipid lowering with atorvastatin in patients with stable coronary disease. In: New England Journal of Medicine. 2005 ; Vol. 352, No. 14. pp. 1425-1435.
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AU - LaRosa, John C.

AU - Grundy, Scott M

AU - Waters, David D.

AU - Shear, Charles

AU - Barter, Philip

AU - Fruchart, Jean Charles

AU - Gotto, Antonio M.

AU - Greten, Heiner

AU - Kastelein, John J P

AU - Shepherd, James

AU - Wenger, Nanette K.

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N2 - BACKGROUND: Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). METHODS: A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. RESULTS: The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. CONCLUSIONS: Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.

AB - BACKGROUND: Previous trials have demonstrated that lowering low-density lipoprotein (LDL) cholesterol levels below currently recommended levels is beneficial in patients with acute coronary syndromes. We prospectively assessed the efficacy and safety of lowering LDL cholesterol levels below 100 mg per deciliter (2.6 mmol per liter) in patients with stable coronary heart disease (CHD). METHODS: A total of 10,001 patients with clinically evident CHD and LDL cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) were randomly assigned to double-blind therapy and received either 10 mg or 80 mg of atorvastatin per day. Patients were followed for a median of 4.9 years. The primary end point was the occurrence of a first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. RESULTS: The mean LDL cholesterol levels were 77 mg per deciliter (2.0 mmol per liter) during treatment with 80 mg of atorvastatin and 101 mg per deciliter (2.6 mmol per liter) during treatment with 10 mg of atorvastatin. The incidence of persistent elevations in liver aminotransferase levels was 0.2 percent in the group given 10 mg of atorvastatin and 1.2 percent in the group given 80 mg of atorvastatin (P<0.001). A primary event occurred in 434 patients (8.7 percent) receiving 80 mg of atorvastatin, as compared with 548 patients (10.9 percent) receiving 10 mg of atorvastatin, representing an absolute reduction in the rate of major cardiovascular events of 2.2 percent and a 22 percent relative reduction in risk (hazard ratio, 0.78; 95 percent confidence interval, 0.69 to 0.89; P<0.001). There was no difference between the two treatment groups in overall mortality. CONCLUSIONS: Intensive lipid-lowering therapy with 80 mg of atorvastatin per day in patients with stable CHD provides significant clinical benefit beyond that afforded by treatment with 10 mg of atorvastatin per day. This occurred with a greater incidence of elevated aminotransferase levels.

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