TY - JOUR
T1 - Safety and Efficacy of Atorvastatin-Induced Very Low-Density Lipoprotein Cholesterol Levels in Patients With Coronary Heart Disease (a Post Hoc Analysis of the Treating to New Targets [TNT]
AU - LaRosa, John C.
AU - Grundy, Scott M
AU - Kastelein, John J P
AU - Kostis, John B.
AU - Greten, Heiner
N1 - Funding Information:
The TNT study was funded by Pfizer, Inc. (New York, New York). The steering committee developed the protocol in collaboration with the funding source and took responsibility for the final version. ICON Clinical Research (North Wales, Pennsylvania) managed all data. ICON and Pfizer provided site monitoring throughout the study. The data were analyzed by the funding source according to the statistical analysis plan approved by the steering committee. The steering committee had unrestricted, request-based access to the study data, which were retained by the funding source, and developed the report independently, without constraints from the sponsor. We take responsibility for the integrity of the data. All investigators have read and agree to the report as written.
PY - 2007/9/1
Y1 - 2007/9/1
N2 - Study)††Conflicts of interest: Dr. LaRosa has served as a consultant to Pfizer, Inc., New York, New York; Merck Whitehouse Station, New Jersey; Bristol-Myers Squibb, New York, New York; and AstraZeneca, Wilmington, Delaware; and has received lecture fees from Pfizer. Dr. Grundy has consulted with Abbott, Chicago, Illinois; GlaxoSmithKline, Durham, North Carolina, Pfizer, AstraZeneca, and Sanofi-Aventis, Bridgewater, New Jersey; received lecture fees from Merck Schering Plough, Kenilworth, New Jersey; Kos, Edison, New Jersey, Pfizer, GlaxoSmithKline, Lilly, and Bristol-Myers Squibb; and received research support from Abbott and GlaxoSmithKline. Dr. Kastelein has received consulting fees, lecture fees, and grant support from Pfizer, Merck Schering Plough, Bristol-Myers Squibb, and Sankyo, Munich, Germany; Dr. Kostis has served as a consultant to Pfizer, Schering Plough, Berlex, Montville, New Jersey; Taisho, Tokyo, Japan; Forest Laboratories, New York, New York; and Sankyo; received lecture fees from Pfizer, Merck, Bristol-Myers Squibb, AstraZeneca, Sanofi Aventis, and Otsuka, Rockville, Maryland; and received grant support from Pfizer and Schering Plough. Dr. Greten has received consulting and lecturing fees from Pfizer, Merck, Schering Plough, and Kowa Company, Nagoya, Japan. High-dose statin therapy has been demonstrated to provide incremental benefit when low-density lipoprotein (LDL) cholesterol concentrations are lowered well below recommended target levels. This secondary analysis of the Treating to New Targets (TNT) study was conducted to investigate whether the attainment of very low LDL cholesterol levels was associated with a further reduction in major cardiovascular events compared with higher LDL cholesterol concentrations and whether any incremental benefit was achieved without additional safety risk. Patients with coronary heart disease and LDL cholesterol levels <130 mg/dl (3.4 mmol/L) were randomized to therapy with atorvastatin 10 mg/day (n = 5,006) or 80 mg/day (n = 4,995). The primary end point was the occurrence of a first major cardiovascular event. Clinical outcomes and safety data were compared across on-treatment LDL cholesterol quintiles. There was a highly significant reduction in the rate of major cardiovascular events with descending achieved levels of on-treatment LDL cholesterol (p <0.0001 for trend across LDL cholesterol). Analysis of individual components of the primary end point demonstrated similar results. Death from any cause and from noncardiovascular causes was lowest in patients with the lowest on-treatment LDL cholesterol levels. Cardiovascular deaths were also reduced with lower levels of on-treatment LDL cholesterol. There were no clinically important differences in adverse event rates across quintiles. Specifically, no increase in muscle complaints, suicide, hemorrhagic stroke, or cancer deaths was observed at the lowest LDL cholesterol levels. In conclusion, the present analysis adds support to the concept that for patients with established atherosclerotic cardiovascular disease, a further risk reduction without sacrifice of safety can be achieved by reducing LDL cholesterol to very low levels.
AB - Study)††Conflicts of interest: Dr. LaRosa has served as a consultant to Pfizer, Inc., New York, New York; Merck Whitehouse Station, New Jersey; Bristol-Myers Squibb, New York, New York; and AstraZeneca, Wilmington, Delaware; and has received lecture fees from Pfizer. Dr. Grundy has consulted with Abbott, Chicago, Illinois; GlaxoSmithKline, Durham, North Carolina, Pfizer, AstraZeneca, and Sanofi-Aventis, Bridgewater, New Jersey; received lecture fees from Merck Schering Plough, Kenilworth, New Jersey; Kos, Edison, New Jersey, Pfizer, GlaxoSmithKline, Lilly, and Bristol-Myers Squibb; and received research support from Abbott and GlaxoSmithKline. Dr. Kastelein has received consulting fees, lecture fees, and grant support from Pfizer, Merck Schering Plough, Bristol-Myers Squibb, and Sankyo, Munich, Germany; Dr. Kostis has served as a consultant to Pfizer, Schering Plough, Berlex, Montville, New Jersey; Taisho, Tokyo, Japan; Forest Laboratories, New York, New York; and Sankyo; received lecture fees from Pfizer, Merck, Bristol-Myers Squibb, AstraZeneca, Sanofi Aventis, and Otsuka, Rockville, Maryland; and received grant support from Pfizer and Schering Plough. Dr. Greten has received consulting and lecturing fees from Pfizer, Merck, Schering Plough, and Kowa Company, Nagoya, Japan. High-dose statin therapy has been demonstrated to provide incremental benefit when low-density lipoprotein (LDL) cholesterol concentrations are lowered well below recommended target levels. This secondary analysis of the Treating to New Targets (TNT) study was conducted to investigate whether the attainment of very low LDL cholesterol levels was associated with a further reduction in major cardiovascular events compared with higher LDL cholesterol concentrations and whether any incremental benefit was achieved without additional safety risk. Patients with coronary heart disease and LDL cholesterol levels <130 mg/dl (3.4 mmol/L) were randomized to therapy with atorvastatin 10 mg/day (n = 5,006) or 80 mg/day (n = 4,995). The primary end point was the occurrence of a first major cardiovascular event. Clinical outcomes and safety data were compared across on-treatment LDL cholesterol quintiles. There was a highly significant reduction in the rate of major cardiovascular events with descending achieved levels of on-treatment LDL cholesterol (p <0.0001 for trend across LDL cholesterol). Analysis of individual components of the primary end point demonstrated similar results. Death from any cause and from noncardiovascular causes was lowest in patients with the lowest on-treatment LDL cholesterol levels. Cardiovascular deaths were also reduced with lower levels of on-treatment LDL cholesterol. There were no clinically important differences in adverse event rates across quintiles. Specifically, no increase in muscle complaints, suicide, hemorrhagic stroke, or cancer deaths was observed at the lowest LDL cholesterol levels. In conclusion, the present analysis adds support to the concept that for patients with established atherosclerotic cardiovascular disease, a further risk reduction without sacrifice of safety can be achieved by reducing LDL cholesterol to very low levels.
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U2 - 10.1016/j.amjcard.2007.03.102
DO - 10.1016/j.amjcard.2007.03.102
M3 - Article
C2 - 17719314
AN - SCOPUS:34547970751
SN - 0002-9149
VL - 100
SP - 747
EP - 752
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 5
ER -