About 18,000 participants with acute coronary syndrome and LDL 50-125 received either zetia plus zocor, or zocor alone. After seven years of follow up, authors found that addition of zetia improved cardiovascular outcomes more in patients with diabetes then those without diabetes. Findings are consistent with the notion that diabetics are at higher baseline CVD risk.

Also see:

Circulation

IMPROVE-IT

January 2018

Background

Ezetimibe, when added to simvastatin, reduces cardiovascular events following acute coronary syndrome (ACS); we explored outcomes stratified by diabetes mellitus (DM).

Methods

In IMPROVE-IT, 18,144 patients post ACS with LDL-C 50-125 mg/dL were randomized to ezetimibe/simvastatin-40mg (E/S) or placebo/simvastatin-40mg (P/S).

Primary composite endpoint was cardiovascular death, major coronary events, and stroke. DM was a prespecified subgroup.

Results

The 4933 (27%) patients with DM were more often older, female, with prior MI and revascularization, and presented more frequently with non-ST segment elevation ACS compared to non-DM (each p<0.001). The median admission LDL-C was lower among patients with DM (89 vs. 97 mg/dL, p<0.001).

Ezetimibe/simvastatin-40mg achieved a significantly lower median time-weighted average LDL-C compared to P/S, irrespective of DM (DM: 49 vs. 67 mg/dL; No DM: 55 vs. 71 mg/dL, both P<0.001).

In DM patients, ezetimibe/simvastatin-40mg reduced the 7-year Kaplan-Meier primary endpoint event rate by 5.5% absolute (HR 0.85; p<0.05); in non-DM patients the absolute difference was 0.7% (HR 0.98; 95% CI, 0.91-1.04; Pinteraction=0.02).

The largest relative reductions in DM patients were in MI (24%) and ischemic stroke (39%). No differences in safety outcomes by treatment were present regardless of DM. When stratified further by age, patients ≥75 years had a 20% relative reduction in the primary endpoint regardless of DM (Pinteraction=0.91), while patients <75 years with DM had greater benefit than those without (Pinteraction=0.011).

When stratified by the TIMI risk score for Secondary Prevention, all patients with DM demonstrated benefit with Ezetimibe/simvastatin-40mg regardless of risk. In contrast, among non-diabetics, patients with a high risk score experienced a significant 18% relative reduction in the composite of cardiovascular death, MI, and ischemic stroke with E/S compared to P/S, whereas non-diabetics at low or moderate risk demonstrated no benefit with the addition of ezetimibe to simvastatin.

Conclusions

In IMPROVE-IT the benefit of adding ezetimibe to statin was enhanced in patients with DM and in high-risk non-diabetics.