Treating to New Targets (TNT) Study: does lowering low-density lipoprotein cholesterol levels below currently recommended guidelines yield incremental clinical benefit?

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Abstract

The Treating to New Targets (TNT) trial is a parallel-group study that has randomized 10,003 patients from 14 countries to double-blind treatment with either atorvastatin 10 or 80 mg. During the double-blind period, low-density lipoprotein (LDL) cholesterol levels are expected to reach approximate mean values of 100 mg/dl (2.6 mmol/L) for the low-dose atorvastatin group and 75 mg/dl (1.9 mmol/L) for the high-dose group. Randomized patients are expected to be followed for an average of 5 years. The primary end point is the time to occurrence of a major cardiovascular event, defined as coronary heart disease death, nonfatal myocardial infarction, resuscitated cardiac arrest, or stroke. The large patient numbers in the TNT study and long follow-up should ensure that there is adequate power to definitively determine if reducing LDL cholesterol levels to approximately 75 mg/dl (1.9 mmol/L) can provide additional clinical benefit.

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Treating to new targets (TNT) Study

The primary hypothesis of the TNT study is that incremental reduction in cardiovascular risk can be achieved by lowering LDL cholesterol levels beyond currently recommended minimum targets. To test the hypothesis, 2 doses of atorvastatin (10 and 80 mg once daily) are being used in a double-blind parallel group design. The occurrence of major cardiovascular end points will be compared in 2 groups of patients: 1 that achieves an average LDL cholesterol of approximately 100 mg/dl (2.6 mmol/L) and

Baseline data from the TNT study

The TNT population is comprised of patients from 14 countries across 4 continents. The first patient was recruited in April 1998. Randomizations occurred from July 1998 to December 1999. Of the 18,468 patients screened, 15,432 entered the open-label run-in period and 10,003 were randomized to double-blind treatment with either atorvastatin 10 or 80 mg (Figure 1).

Selected baseline characteristics of randomized patients are shown in Table 1. Serum lipid concentrations at baseline are given in

Discussion

Other trials due for completion in the next few years should provide results that will be complementary to the results of TNT. The Incremental Decrease in Endpoints through Aggressive Lipid Lowering (IDEAL) study is comparing atorvastatin 80 mg/day with simvastatin 20 to 40 mg/day in 8,888 coronary patients to examine whether a higher dose of a stronger statin provides additional coronary benefit. The Study of the Effectiveness of Additional Reductions of Cholesterol and Homocysteine (SEARCH)

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This study was supported by a research grant from Pfizer Inc., Groton, Connecticut.

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A list of members and investigators appears in the Appendix.

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