Abstract 2455: Intensive Statin Therapy Reduces Risk of Cardiovascular Disease Beyond Occurrence of the First Event: Analysis of the Incremental Decrease in Endpoints through Aggressive Lipid Lowering Trial
Background: Primary and secondary endpoints of statin trials generally refer to time to occurrence of first endpoint event. However, a significant number of all events that occur during the course of a trial occur subsequent to the first event. In the Incremental Decrease in Endpoints through Aggressive Lipid Lowering trial (IDEAL), which compared intensive statin therapy with atorvastatin 80 mg (A80) to standard therapy with simvastatin 20 – 40 mg (S20 – 40) in 8888 coronary heart disease (CHD) patients, the primary endpoint of major coronary event (MCE, a composite of time to first occurrence of nonfatal myocardial infarction, CHD death, or resuscitated cardiac arrest) was reduced by 11%, p=0.07, with A80. The broader secondary endpoint of any cardiovascular (CV) event (a composite of time to first occurrence of MCE, stroke, unstable angina, hospitalization for congestive heart failure, or peripheral artery disease) was significantly reduced by 16%, p<0.0001, with A80. We hypothesized that A80 also resulted in reduction of risk for occurrence of any CV event that occurred subsequent to occurrence of the first CV event.
Methods: All reported CV endpoints in the IDEAL trial were adjudicated. Because the majority of events during the course of the trial were nonfatal and there were subjects with <1 event, we conducted a posthoc time-to-event analysis to estimate the treatment hazard ratio separately for the time to first, second, third, fourth, and fifth events.
Results: There were 1048 patients with a second CV event, 416 with a third, 192 with a fourth and 93 with a fifth event. Patients randomized to A80 compared to those randomized to S20 – 40 had reduction in the relative risk of second event by 24% (p<0.0001), of third event by 19% (p=0.03), of fourth event by 24% (=0.06) and of fifth event by 28% (p=0.12).
Conclusions: This analysis of all events that occurred during the course of the IDEAL trial indicates that over time, beyond the reduction in risk of first CV event, intensive treatment with A80 continued to reduce risk of any CV event more than standard therapy with S20 – 40.