Outcomes of Using High- or Low-Dose Atorvastatin in Patients 65 Years
of Age or Older with Stable Coronary Heart Disease

Nanette K. Wenger, MD; Sandra J. Lewis, MD; David M. Herrington, MD;
Vera Bittner, MD; Francine K. Welty, MD, PhD, for the Treating to New
Targets Study Steering Committee and Investigators

Annals of Internal Medicine, 3 July 2007 | Volume 147 Issue 1 | Pages
1-9

Background: Increased life expectancy is associated with an increase
in the burden of chronic cardiovascular disease.

Objective: To assess the efficacy and safety of high-dose atorvastatin
in patients 65 years of age or older.

Design: A prespecified secondary analysis of the Treating to New
Targets study, a randomized, double-blind clinical trial.

Setting: 256 sites in 14 countries participating in the Treating to
New Targets study.

Participants: 10 001 patients (3809 patients 65 years of age) with
coronary heart disease (CHD) and low-density lipoprotein cholesterol
levels less than 3.4 mmol/L (<130 mg/dL).

Intervention: Patients were randomly assigned to receive atorvastatin,
10 or 80 mg/d.

Measurements: The primary end point was the occurrence of a first
major cardiovascular event (death from CHD, nonfatal non-procedure-
related myocardial infarction, resuscitated cardiac arrest, or fatal
or nonfatal stroke).

Results: In patients 65 years of age or older, absolute risk was
reduced by 2.3% and relative risk by 19% for major cardiovascular
events in favor of the high-dose atorvastatin group (hazard ratio,
0.81 [95% CI, 0.67 to 0.98]; P = 0.032). Among the components of the
composite outcome, the mortality rates from CHD, nonfatal non-
procedure-related myocardial infarction, and fatal or nonfatal stroke
(ischemic, embolic, hemorrhagic, or unknown origin) were all lower in
older patients who received high-dose atorvastatin, although the
difference was not statistically significant for each individual
component. The improved clinical outcome in patients 65 years of age
or older was not associated with persistent elevations in creatine
kinase levels.

Limitation: Because the study was a secondary analysis, the findings
should be interpreted within the context of the main study results.

Conclusions: The analysis suggests that additional clinical benefit
can be achieved by treating older patients with CHD more aggressively
to reduce low-density lipoprotein cholesterol levels to less than 2.6
mmol/L (<100 mg/dL). The findings support the use of intensive low-
density lipoprotein cholesterol-lowering therapy in high-risk older
persons with established cardiovascular disease.

*  *  *
It's possible somebody has already posted this, but I didn't find it.

It's hard to get too excited about the absolute risk reduction
demonstrated here, especially with apparently no demonstrated
reduction in all-cause mortality.

There's something I don't understand.  I read a description of the TNT
study and it said some of the people had already had an MI.  In that
case, how can the primary endpoint be occurrence of first
cardiovascular event?

Marilyn