ORLANDO Driving low density lipoprotein levels below 100
mg/dL with atorvastatin significantly improved outcomes compared to what was
observed at the 100-mg/dL threshold.
We have entered a new era in the treatment of established
coronary disease, John LaRosa, MD, president of State University
New York Downstate, said at the American College of Cardiology Annual
Scientific Session 2005. These data extend the body of evidence
indicating that lowering LDL well below currently recommended levels can
further reduce the health care burden associated with cardiovascular and
LaRosa presented results from the Treating to New Targets (TNT)
study, which randomized 10,001 patients, from 256 sites in 14 countries, to
either 10 mg or 80 mg of atorvastatin (Lipitor, Pfizer).
Patients entered the trial after a washout period to remove all
lipid lowering therapies, and initially all patients were placed on 10 mg of
atorvastatin to reduce their LDL cholesterol to about 100 mg/dL.
After this initial treatment period, half the patients were placed
on 80 mg of atorvastatin with the goal of reducing LDL to approximately 75
The mean age of patients was 61. Most of the patients were white,
and about 80% were male. All patients had a history of established coronary
disease, about half had hypertension, and 15% had diabetes.
Researchers excluded all patients with LDL >130 mg/dL.
All patients achieved an LDL of about 101 mg/dL prior to
randomization to either low-dose or high-dose atorvastatin. After 4.9 years of
follow-up, those patients taking 80 mg of atorvastatin had achieved a mean LDL
of 77 mg/dL. Total cholesterol and triglycerides were also significantly
improved in the high-dose group, but HDL remained the same between the two
Researchers assessed a primary composite outcome of a first major
cardiovascular event, defined as death from coronary heart disease, nonfatal
MI, resuscitation after cardiac arrest or fatal and nonfatal stroke.
Patients in the high-dose atorvastatin arm had an 8.7% rate of the
primary outcome compared to 10.9% in the low-dose group, a significant
(P<.001) 22% risk reduction.
The reduction of LDL below 100 mg/dL also produced
significant clinical benefits beyond the coronary vasculature, LaRosa
said. We singled out stroke because of the potential for severe long-term
physical and mental disability and the huge economic burden this presents for
society. Intensive therapy with atorvastatin reduced the risk of stroke by
TNT was not powered to detect a difference in mortality, so there
was no difference in all-cause mortality between the two groups.
In a group of 10,000 patients with documented coronary heart
disease followed for five years on atorvastatin, cardiovascular death was not
the leading cause of death. The leading cause of death in both groups was
cancer, LaRosa said.
Patients taking 80 mg of atorvastatin were more likely to
experience an adverse event (8.1% vs. 5.8%, P<.001). No
specific category of events could be identified to account for these
differences, LaRosa said. Treatment-related myalgia was reported in 4.8%
of the high-dose group and 4.7% of the low-dose group (P=.72). Two cases
of rhabdomyolysis were reported in the high-dose group compared to three in the
In a comment period following LaRosas presentation, Carl J.
Vaughan, MD, University College Cork in Ireland, said TNT was a proof of
concept study that confirms what has been shown in PROVE-IT and the Heart
When we look back at the dozen or so statin trials that we have to
date, the overriding message is the absolute importance of bringing statin
therapy to patients at risk and to wider populations such as hypertensives and
diabetics, Vaughan said. by Jeremy Moore
For more information:
- LaRosa JC. Effect of lowering low density lipoprotein
cholesterol substantially below currently recommended levels in patients with
coronary heart disease: results of the Treating to New Targets study.
Late-breaking trial presented at the American College of Cardiology Annual
Scientific Session 2005. March 6-9, 2005. Orlando.