The Improved Reduction of Outcomes: Vytorin Efficacy International Trial, presented Monday morning at the American Heart Association meeting in Chicago, randomized 18,144 high-risk patients within 10 days of an acute coronary event to either ezetimibe or placebo on top of a statin. These patients had LDL levels between 50-125 mg/dL, or between 50-100 mg/dL if on a prior cholesterol drug. Patients were followed for an average of six years. The trial ended after there were 5,250 primary endpoint events (CV death, MI, hospital admission for unstable angina, coronary revascularization more than a month after randomization, or stroke).
Primary endpoint events occurred in 34.7% of the control group versus 32.7% of the treatment group, representing a 6.4% reduction in risk (HR 0.936, CI 0.887-0.988, p=0.016). The investigators calculated that 50 patients would need to be treated for seven years to prevent one event.
The NNT of 50, when spread out over 6 years, is not huge. This represents a modest incremental benefit which is the best we would have reasonably hoped for given that the patients were already on statins and their baseline LDL levels were low.
The real impact of this study, in my view, is on the debate over whether LDL lowering matters. Findings about the pleiotropic effects of statins in recent years somehow led to the notion that LDL reduction was irrelevant. That simplistic thinking took hold despite lots of prior evidence that LDL reduction reduced cardiovascular events no matter by what means. Some even spun the new lipid guidelines as a debunking of the LDL hypothesis. IMPROVE-IT adds further support to LDL reduction.