Effects of High-Dose Atorvastatin on Cerebrovascular Events in Patients With Stable Coronary Disease in the TNT (Treating to New Targets) Study

David D. Waters, John C. LaRosa, Philip Barter, Jean Charles Fruchart, Antonio M. Gotto, Roddy Carter, Andrei Breazna, John J P Kastelein, Scott M Grundy

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Abstract

Objective: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl. Background: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated. Methods: We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years. Results: Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95% confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95% CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95% CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6% relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5% relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment. Conclusions: Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).

Original languageEnglish (US)
Pages (from-to)1793-1799
Number of pages7
JournalJournal of the American College of Cardiology
Volume48
Issue number9
DOIs
StatePublished - Nov 7 2006

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LDL Cholesterol
Coronary Disease
Stroke
Confidence Intervals
Risk Reduction Behavior
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Atorvastatin Calcium
Observational Studies
Therapeutics
Cholesterol
Incidence

ASJC Scopus subject areas

  • Nursing(all)

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Effects of High-Dose Atorvastatin on Cerebrovascular Events in Patients With Stable Coronary Disease in the TNT (Treating to New Targets) Study. / Waters, David D.; LaRosa, John C.; Barter, Philip; Fruchart, Jean Charles; Gotto, Antonio M.; Carter, Roddy; Breazna, Andrei; Kastelein, John J P; Grundy, Scott M.

In: Journal of the American College of Cardiology, Vol. 48, No. 9, 07.11.2006, p. 1793-1799.

Research output: Contribution to journalArticle

Waters, David D. ; LaRosa, John C. ; Barter, Philip ; Fruchart, Jean Charles ; Gotto, Antonio M. ; Carter, Roddy ; Breazna, Andrei ; Kastelein, John J P ; Grundy, Scott M. / Effects of High-Dose Atorvastatin on Cerebrovascular Events in Patients With Stable Coronary Disease in the TNT (Treating to New Targets) Study. In: Journal of the American College of Cardiology. 2006 ; Vol. 48, No. 9. pp. 1793-1799.
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abstract = "Objective: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl. Background: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated. Methods: We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years. Results: Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95{\%} confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95{\%} CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95{\%} CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6{\%} relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5{\%} relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment. Conclusions: Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20{\%} to 25{\%} compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).",
author = "Waters, {David D.} and LaRosa, {John C.} and Philip Barter and Fruchart, {Jean Charles} and Gotto, {Antonio M.} and Roddy Carter and Andrei Breazna and Kastelein, {John J P} and Grundy, {Scott M}",
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T1 - Effects of High-Dose Atorvastatin on Cerebrovascular Events in Patients With Stable Coronary Disease in the TNT (Treating to New Targets) Study

AU - Waters, David D.

AU - LaRosa, John C.

AU - Barter, Philip

AU - Fruchart, Jean Charles

AU - Gotto, Antonio M.

AU - Carter, Roddy

AU - Breazna, Andrei

AU - Kastelein, John J P

AU - Grundy, Scott M

PY - 2006/11/7

Y1 - 2006/11/7

N2 - Objective: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl. Background: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated. Methods: We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years. Results: Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95% confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95% CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95% CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6% relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5% relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment. Conclusions: Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).

AB - Objective: We sought to assess the effects on cerebrovascular events of treating patients with stable coronary disease with low-density lipoprotein cholesterol (LDL-C) levels substantially below 100 mg/dl. Background: Lowering LDL-C with statins has been shown to reduce the risk of stroke in patients with stable coronary disease. In observational studies, naturally low cholesterol levels have been associated with an increased risk of hemorrhagic stroke. The cerebrovascular benefits of treating patients with stable coronary disease to LDL-C levels substantially below 100 mg/dl have not been previously investigated. Methods: We describe an analysis of cerebrovascular events in the Treating to New Targets study, a trial where 10,001 patients with documented coronary disease were randomized to treatment with atorvastatin at 10 mg/day or 80 mg/day and followed for a median of 4.9 years. Results: Mean LDL-C levels were 101 mg/dl on 10 mg atorvastatin and 77 mg/dl on 80 mg. In addition to the reduction in major cardiovascular events (hazard ratio 0.78, 95% confidence interval [CI] 0.69 to 0.89; p = 0.0002), the primary end point of the trial, patients in the 80-mg arm experienced a reduction in cerebrovascular events (hazard ratio 0.77, 95% CI 0.64 to 0.93; p = 0.007) and stroke (hazard ratio 0.75, 95% CI 0.59 to 0.96; p = 0.02). Each 1-mg/dl reduction in LDL-C with treatment was associated with a 0.6% relative risk reduction in cerebrovascular events (p = 0.002) and a 0.5% relative risk reduction in stroke (p = 0.041). The incidence of hemorrhagic stroke was similar in the 80-mg and 10-mg groups, 16 and 18 respectively, and the hemorrhagic strokes were distributed evenly across quintiles of achieved LDL-C during treatment. Conclusions: Among patients with established coronary disease, treating to an LDL-cholesterol substantially below 100 mg/dl with 80 mg/day atorvastatin reduces both stroke and cerebrovascular events by an additional 20% to 25% compared with the 10 mg/day dose. An increase in hemorrhagic stroke was not seen at low LDL-C levels. (Treating to New Targets; http://www.clinicaltrials.gov; NCT00327691).

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