Clinical Question: Is intensive lowering of serum lipid levels with statin drugs beneficial in patients with stable coronary artery disease (CAD)?

Setting: Outpatient (specialty)

Study Design: Randomized controlled trial (single-blinded)

Allocation: Uncertain

Synopsis: Intensive lowering of low-density lipoprotein (LDL) cholesterol to less than 100 mg per dL (2.6 mmol per L) is beneficial for patients with acute coronary syndromes. It is uncertain, however, if similar treatment provides further benefit in stable CAD. The investigators enrolled 8,888 adults from 190 ambulatory cardiology care and subspecialist practices in northern Europe. The patients were 80 years or younger and had a history of myocardial infarction. They were randomly assigned (uncertain allocation concealment) to receive a high dose of atorvastatin ([Lipitor] 80 mg per day) or usual-dose simvastatin ([Zocor] 20 mg per day). If, after 24 weeks of monitoring, the plasma total cholesterol level was higher than 190 mg per dL (5.0 mmol per L), the dose of simvastatin could be increased to 40 mg per day. Follow-up occurred for nearly 100 percent of patients for 4.8 years. Individuals assessing outcomes were blinded to treatment group assignment. The primary outcome was recurrence of a major coronary event, defined as coronary death, hospitalization for nonfatal acute myocardial infarction, or cardiac arrest with resuscitation. During treatment, mean LDL levels were 104 mg per dL (2.7 mmol per L) in the simvastatin group and 81 mg per dL (2.1 mmol per L) in the atorvastatin group.

Using intention-to-treat analysis, there was no statistical difference in the reccurrence of a major coronary event between the two groups. The risk of death from any cause, including noncardiovascular causes, also was similar in both groups. The investigators reported a number of different post hoc secondary outcomes showing benefit to intensive lipid lowering, but the important patient-oriented outcomes of living better and living longer are improved little, if at all, with intensive lowering. Discontinuation rates were higher in the atorvastatin group because of adverse events.

Bottom Line: The intensive reduction of LDL levels to less than 100 mg per dL did not result in a significant reduction in the recurrence of major coronary events or all-cause mortality among patients with stable CAD. Intensive lowering is associated with an increased risk of discontinuing medication because of adverse events and significant drug costs. Aiming for an LDL level of approximately 100 mg per dL seems optimal for most patients with stable disease. (Level of Evidence: 1b)