For patients in either study group who had
LDL cholesterol levels higher than 79 mg per
deciliter (2.0 mmol per liter) on two consecutive
measurements, the simvastatin dose was increased
to 80 mg in a double-blind manner. In
June 2011, in accordance with Food and Drug
Administration guidance for limiting new prescriptions
of 80 mg of simvastatin, patients were
no longer eligible for an increased dose of simvastatin
to 80 mg, and any patient who had been
receiving the 80-mg dose for less than 1 year
had the dose reduced to 40 mg.23 If an LDL cholesterol
measurement on the new regimen was
confirmed to be higher than 100 mg per deciliter,
the study drug could be discontinued and
more potent therapy initiated. The study continued
until each patient had been followed for a
minimum of 2.5 years and until the target number
of events (5250) was reached. Five amendments
to the protocol were implemented during
the course of the study, including an increase in
the sample size