23 juin 2016
TNT? : Treating to New Targets.
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).
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.
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).> 15755765
Shepherd J, Barter P, Carmena R, Deedwania P, Fruchart JC, Haffner S, Hsia J, Breazna A, LaRosa J, Grundy S, Waters D. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes : the Treating to New Targets (TNT?) study. Diabetes Care. 2006 Jun ; 29(6):1220-6. 16731999
Deedwania P, Barter P, Carmena R, Fruchart JC, Grundy SM, Haffner S, Kastelein JJ, LaRosa JC, Schachner H, Shepherd J, Waters DD ; Treating to New Targets Investigators. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome : analysis of the Treating to New Targets study. Lancet. 2006 Sep 9 ; 368(9539):919-28. 16962881
Waters DD, LaRosa JC, Barter P, Fruchart JC, Gotto AM Jr, Carter R, Breazna A, Kastelein JJ, Grundy SM. Effects of high-dose atorvastatin on cerebrovascular events in patients with stable coronary disease in the TNT? (treating to new targets) study. J Am Coll Cardiol. 2006 Nov 7 ; 48(9):1793-9. 17084252
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Bangalore S, Messerli FH, Wun CC, Zuckerman AL, DeMicco D, Kostis JB, LaRosa JC ; Treating to New Targets Steering Committee and Investigators. J-curve revisited : An analysis of blood pressure and cardiovascular events in the Treating to New Targets (TNT?) Trial. Eur Heart J. 2010 Dec ; 31(23):2897-908. 20846991
Frey P, Waters DD, DeMicco DA?, Breazna A, Samuels L, Pipe A, Wun CC, Benowitz NL. Impact of smoking on cardiovascular events in patients with coronary disease receiving contemporary medical therapy (from the Treating to New Targets [TNT?] and the Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] trials). Am J Cardiol. 2011 Jan 15 ; 107(2):145-50. 21129718
Mora S, Wenger NK, Demicco DA?, Breazna A, Boekholdt SM, Arsenault BJ, Deedwania P, Kastelein JJ, Waters DD. Determinants of residual risk in secondary prevention patients treated with high- versus low-dose statin therapy : the Treating to New Targets (TNT?) study. Circulation. 2012 Apr 24 ; 125(16):1979-87. 22461416
Waters DD, Ho JE, Boekholdt SM, DeMicco DA?, Kastelein JJ, Messig M, Breazna A, Pedersen TR. Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy : effect of baseline risk factors for diabetes. J Am Coll Cardiol. 2013 Jan 15 ; 61(2):148-52. 23219296
Relation of improvement in estimated glomerular filtration rate with atorvastatin to reductions in hospitalizations for heart failure (from the Treating to New Targets [TNT?] study).
Ho JE, Waters DD, Kean A, Wilson DJ, Demicco DA?, Breazna A, Wun CC, Deedwania PC, Khush KK ; TNT? Investigators.
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Dorresteijn JA, Boekholdt SM, van der Graaf Y, Kastelein JJ, LaRosa JC, Pedersen TR, DeMicco DA?, Ridker PM, Cook NR, Visseren FL. High-dose statin therapy in patients with stable coronary artery disease : treating the right patients based on individualized prediction of treatment effect. Circulation. 2013 Jun 25 ; 127(25):2485-93. 23674398
Arsenault BJ, Boekholdt SM, Mora S, DeMicco DA, Bao W, Tardif JC, Amarenco P, Pedersen T, Barter P, Waters DD. Impact of high-dose atorvastatin therapy and clinical risk factors on incident aortic valve stenosis in patients with cardiovascular disease (from TNT?, IDEAL, and SPARCL). Am J Cardiol. 2014 Apr 15 ; 113(8):1378-82. 24582532
Bangalore S, Breazna A, DeMicco DA?, Wun CC, Messerli FH ; TNT? Steering Committee and Investigators. Visit-to-visit low-density lipoprotein cholesterol variability and risk of cardiovascular outcomes : insights from the TNT? trial. J Am Coll Cardiol. 2015 Apr 21 ; 65(15):1539-48. 25881936
Deedwania PC, Shepherd J, Breazna A, DeMicco DA? ; Treating to New Targets (TNT?) Steering Committee Investigators. Effect of high-dose atorvastatin on the cardiovascular risk associated with individual components of metabolic syndrome : a subanalysis of the Treating to New Targets (TNT?) study. Diabetes Obes Metab. 2016 Jan ; 18(1):56-63. 26434404
Shepherd J, Breazna A, Deedwania PC, LaRosa JC, Wenger NK, Messig M, Wilson DJ ; Treating to New Targets Steering Committee and Investigators. Relation Between Change in Renal Function and Cardiovascular Outcomes in Atorvastatin-Treated Patients (from the Treating to New Targets [TNT?] Study). Am J Cardiol. 2016 Apr 15 ; 117(8):1199-205. 26940556
Deedwania PC, Pedersen TR, DeMicco DA?, Breazna A, Betteridge DJ, Hitman GA, Durrington P, Neil A ; TNT?, CARDS and IDEAL Steering Committees and Investigators. Differing predictive relationships between baseline LDL-C, systolic blood pressure, and cardiovascular outcomes. Int J Cardiol. 2016 Jul 30 ; 222:548-556. 27513651