TNT and Diabetes - Any real benefit with Atorvostatin 80 vs 10 mg?

TNT study
Diabetes Care 29:1220-1226, 2006

RESEARCH DESIGN AND METHODS: A total of 1,501 patients with diabetes and CHD, with LDL cholesterol levels of <130 mg/dl, were randomized to double-blind therapy with either atorvastatin 10 (n = 753) or 80 (n = 748) mg/day. Patients were followed for a median of 4.9 years. The primary end point was the time to first major cardiovascular event, defined as death from CHD, nonfatal non-procedure-related myocardial infarction, resuscitated cardiac arrest, or fatal or nonfatal stroke.



Figure 1—Kaplan-Meier estimates of the incidence of major cardiovascular events in patients with diabetes. *Composite of CHD death, nonfatal non– procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke.

Figure 2

Primary efficacy outcome measure: Time to first occurrence of a major cardiovascular event.

Defined as: CHD death, nonfatal non–procedure-related myocardial infarction, resuscitated cardiac arrest, and fatal or nonfatal stroke.

Article's conclusions: Among patients with clinically evident CHD and diabetes, intensive therapy with atorvastatin 80 mg significantly reduced the rate of major cardiovascular events by 25% compared with atorvastatin 10 mg.

Analysis:

Another case of how you slice it? The article claims that there is a reduction of major cardiovascular events by 25% with atorvostatin 80 compared to 10 mg among patients with clinically evident CHD and diabetes. But look at each individual measure that defines "major cardiovascular event":

CHD Death: HR 0.74[0.47-1.18] P=0.203
Non-fatal non-procedure-related myocardial infarction: HR 0.79[0.55-1.14] P=0.202
Resuscitated cardiac arrest: no data provided
Fatal/Non-fatal stroke: HR 0.67[0.43-1.04] P=0.075

Actually none of these measures that have data provided reach significance. I would assume that resuscitated cardiac arrest must, though there is no data provided.

There is no difference in all cause mortality as seen in figure 2. There was a reduction in cardiovascular mortality with 80 mg(5.2%) versus 10 mg (6.5%), but an increase in noncardiovascular mortality in 80 mg(5.6%) versus 10 mg(3.3%). "However, the study was not powered to detect a significant difference between the treatment groups for mortality."

Not powered to detect a significant difference for mortality? Isn't that the ultimate point?

Given the above, I see little if any benefit in automatically prescribing atorvastatin 80 mg versus 10 mg for diabetics as the industry is implying we should do. One wonders as well if there is any benefit to intensive lowering of LDL cholesterol in diabetics.