Ezetimibe Plus Statin Therapy Reduces Ischemic Risk in Polyvascular Disease, T2D

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The addition of ezetimibe to simvastatin reduced ischemic risk compared with placebo, with consistent relative risk reductions in patients with and without polyvascular disease.

Patients with acute coronary syndrome and polyvascular disease may be at long-term increased ischemic vascular risk compared with patients who do not have polyvascular disease. The presence of type 2 diabetes (T2D) with polyvascular disease may increase this risk and may also be associated with a malignant vascular phenotype. Treatment with ezetimibe and simvastatin together may lower risk, especially in patients with both polyvascular disease and T2D, according to study findings published in The Lancet Diabetes & Endocrinology.

In this study, researchers randomly assigned 18,144 individuals who were stabilized after an acute coronary syndrome to receive simvastatin (40 mg/day) and either ezetimibe (10 mg/day) or a placebo. Follow-ups took place at 1 and 4 months into treatment and then every 4 months for a median of 6.6 years. During the trial, patients in both groups with low-density lipoprotein cholesterol readings >79 mg/dL on 2 successive measurements had simvastatin dosage increased to 80 mg/day. Disease event rates were expressed at 7 years.

Results indicated that 1005 patients had peripheral artery disease and 1071 had a stroke or transient ischemic attack at baseline. Of these participants, 388 and 409 also had T2D, respectively. At 7 years, patients with polyvascular disease or T2D had similar ischemic vascular risk rates. Patients taking ezetimibe showed reduced risk at each follow-up with greatest risk reductions in the highest risk subgroups. Patients with T2D had relative risk reductions with ezetimibe regardless of polyvascular disease diagnosis (T2D without polyvascular disease: hazard ratio [HR], 0.83; 95% CI, 0.75-0.93; T2D with polyvascular disease: HR, 0.91; 95% CI, 0.74-1.12), with noted absolute risk reductions of approximately 5% in the group without vascular disease and 9% in the group with vascular disease at year 7.

Researchers concluded that “the addition of ezetimibe to simvastatin reduced [ischemic] risk compared with placebo, with consistent relative risk reductions in patients with and without polyvascular disease. By nature of their greater absolute risk, however, patients with polyvascular disease, and particularly those who also had concomitant type 2 diabetes, seemed to derive greater absolute benefit.”

The research group declared funding from drug companies. See reference for a full list of disclosures.

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Bonaca MP, Gutierrez JA, Cannon C, et al. Polyvascular disease, type 2 diabetes, and long-term vascular risk: a secondary analysis of the IMPROVE-IT trial [published November 2, 2018]. Lancet Diabetes Endocrinol. doi:10.1016/s2213-8587(18)30290-0