The Third Report of the National Cholesterol Education Program ( NCEP ) - Adult Treatment Panel and the most recent guidelines of the Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice have recommended an LDL cholesterol level of less than 100 mg per deciliter as the goal of therapy for patients at high risk for coronary heart disease ( CHD ).
On the basis of data from HPS and PROVE IT trials, the NCEP in conjunction with the American Heart Association and the American College of Cardiology subsequently introduced a more aggressive, but optional, LDL-cholesterol goal of less than 70 mg per deciliter ( 1.8 mmol per liter ) for patients at very high risk for CHD.
The aim of TNT ( Treating to New Targets ) trial was to assess the hypothesis that reducing LDL-cholesterol levels to well below 100 mg per deciliter in patients with stable CHD and slightly elevated LDL-cholesterol levels could yield an incremental clinical benefit.
One group of patients was randomized to receive 10 mg of Atorvastatin ( Lipitor ) daily with the goal of an average LDL-cholesterol level of 100 mg per deciliter,and the other group received 80 mg of Atorvastatin daily with the goal of an average LDL-cholesterol level of 75 mg per deciliter ( 1.9 mmol per liter ).
The primary efficacy end point was the occurrence of a major cardiovascular event, defined as death from CHD, nonfatal non–procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke.
The study was performed on a total of 10.001 patients who were followed for a median of 4.9 years.
As compared with the group given 10 mg of Atorvastatin, the group given 80 mg had a 22 percent relative reduction in the primary composite efficacy end point.
In addition, the patients taking 80 mg of Atorvastatin also had significant reductions in the risk of any coronary event, a cerebrovascular event, hospitalisation with a primary diagnosis of congestive heart failure.
The risk of death from any cause also did not differ significantly between the two drug regimens.
There were 155 deaths from cardiovascular causes in the group given 10 mg of Atorvastatin ( 3.1 percent ) and 126 in the group given 80 mg of Atorvastatin ( 2.5 percent ).
The deaths from non cardiovascular causes were 127 in the group given 10 mg of Atorvastatin ( 2.5 percent ) and 158 in the group given 80 mg of Atorvastatin ( 3.2 percent ).
Cancer accounted for more than half the deaths from non-cardiovascular causes in both groups: 75 in the group given 10 mg of Atorvastatin ( 1.5 percent ) and 85 in the group given 80 mg of Atorvastatin ( 1.7 percent ).
Adverse events occurred in the 8.1 percent in patients receiving 80 mg of Atorvastatin, and in 5.8 percent in the group given 10 mg of Atorvastatin.
The respective rates of discontinuation due to treatment-related adverse events were 7.2 percent and 5.3 percent, respectively.
Myalgia was reported by 241 ( 4.8 percent ) patients in the group taking 80 mg of Atorvastatin and by 234 ( 4.7 percent ) patients in the group given 10 mg of Atorvastatin.
A total of 60 patients receiving 80 mg of Atorvastatin had a persistent elevation in alanine aminotransferase, aspartate aminotransferase (1.2 percent versus 0.2 percent ).
Five cases of rhabdomyolysis were reported: two in the group given 80 mg of Atorvastatin and three in the group given 10 mg of Atorvastatin.
Source: The New England Journal of Medicine, 2005