(Statins) and Fixed-dose Combination Products Containing a Statin

Final Report Update 5 Drug Effectiveness Review Project
patients with diabetes who did not have known coronary or other occlusive arterial disease at
study entry, there was a 33% reduction in first major vascular events (95% CI, 17 to 46;
P=0.0003). The reduction in risk for stroke (24%) in patients with diabetes was also similar to
the reduction in the overall high-risk group. ASPEN was the only trial that showed a small
nonsignificant reduction in the composite primary outcome of cardiovascular deaths or other
cardiovascular events with atorvastatin (Table 10; Evidence Table 2). Potential reasons for not
finding a significant effect may have been due to a change in study protocol within 2 years of the
start of the study, enrollment of “very low risk” patients, and how the primary endpoint was
defined.
There were 2 trials 145, 183 (LIPS, Xu, et al) that studied the effectiveness of fluvastatin 80
mg or atorvastatin 20 mg in patients with diabetes who had undergone percutaneous coronary
interventions. Both trials observed a benefit associated with the study statins compared with
placebo (Table 10; Evidence Table 2). All-cause mortality reported in 1 145 trial was not
significant.
The 4D trial 134 enrolled patients with type 2 diabetes who had end-stage renal disease and
were receiving maintenance hemodialysis (Table 10; Evidence Table 2). After 4 years of followup,
there was no difference between atorvastatin 20 mg and placebo on the primary endpoint or
all-cause mortality despite low-density lipoprotein of 72 mg/dL. There was also an increase in
fatal strokes in the atorvastatin group— although this was likely to be a chance finding— and no
effect on any individual component of the primary endpoint. Authors of 4D speculated that
nonsignificant results for primary outcome may be related to lower baseline low-density
lipoprotein levels, sicker population, and a different pathogenesis of events in this population.
One publication 146 was rated poor quality due to unclear randomization, allocation
concealment, intention-to-treat analysis, and inadequate blinding.
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