IMPROVE-IT analyses show further evidence of benefit from adding ezetimibe to statin therapy

LONDON — Analyses from the IMPROVE-IT study presented at the European Society of Cardiology Congress indicated that adding ezetimibe to simvastatin especially benefited patients with diabetes and did not cause new-onset diabetes.

Researchers also found that, among the 18,144 patients with ACS in the IMPROVE-IT trial assigned ezetimibe (Zetia, Merck) plus simvastatin or simvastatin alone, treatment group was not a predictor of cancer, achievement of very low LDL was not a predictor of safety issues and achieving LDL and high-sensitivity C-reactive protein goals was associated with improved outcomes.

Benefits in patients with diabetes

Robert P. Giugliano, MD, SM, FACC, FAHA, from Brigham and Women’s Hospital and Harvard Medical School, presented a breakdown of the IMPROVE-IT results stratified by patients with and without diabetes.

Robert P. Giugliano

Giugliano and colleagues found that the primary endpoint of CV death, MI, hospitalization for angina, urgent coronary revascularization or stroke was more favorable to the ezetimibe/simvastatin group among those with diabetes (HR = 0.86; 95% CI, 0.78-0.94) than in those without (HR = 0.98; 95% CI, 0.91-1.04; P for interaction = .023).

Among other endpoints, being in the ezetimibe/simvastatin group was more likely to confer better results for MI (P for interaction = .028), ischemic stroke (P for interaction = .031), CV death/MI/ischemic stroke (P for interaction = .016) and the primary endpoint but including all revascularization instead of urgent revascularization (P for interaction = .021) for those with diabetes than without, Giugliano said.

Diabetes onset

Adding ezetimibe to simvastatin in the IMPROVE-IT population did not increase the risk for new-onset diabetes, Michael A. Blazing, MD, from Duke University, reported.

Blazing and colleagues compared the rate of new-onset diabetes, defined as initiation of diabetes medication or two consecutive fasting glucose tests of at least 7 mmol/L, in patients enrolled in IMPROVE-IT who did not have diabetes at baseline.

They found no difference in new-onset diabetes between the simvastatin/ezetimibe group and the simvastatin-alone group (HR = 1.04; 95% CI, 0.94-1.15).

Those who developed new-onset diabetes during the trial were closer in body size and lipid parameters to those who had pre-existing diabetes, but were closer in age and sex to those who did not develop diabetes, Blazing said.

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Cancer and ezetimibe

A poster presented by Giugliano and colleagues concerned a prespecified analysis of cancer in the IMPROVE-IT population. Previous research had indicated a possible link between ezetimibe and increased risk for cancer.

Among those enrolled in IMPROVE-IT, there was no difference between the groups in cancer rate (HR = 1.03; 95% CI, 0.93-1.14) or incidence of cancer-related death (HR = 1.03; 95% CI, 0.87-1.22), they found.

The rates were similar even in high cancer-risk subgroups such as current smokers and the elderly, according to the researchers.

Very low LDL

Those in the IMPROVE-IT population who achieved LDL of 30 mg/dL or less at 1 month, which happened more frequently in the ezetimibe/simvastatin group than in the simvastatin-alone group, had no increased safety risk compared with those who did not, Giugliano said during a presentation.

In fact, he said, those who achieved LDL of 50 mg/dL or less at 1 month had a reduced risk for the primary efficacy endpoint compared with those who did not (adjusted HR = 0.9; 95% CI, 0.85-0.96).

LDL and CRP targets

In another poster, Erin A. Bohula May, MD, DPhil, from Brigham and Women’s Hospital, and colleagues presented findings on achievement of LDL of 70 mg/dL or less and high-sensitivity CRP of less than 2 mg/L in the IMPROVE-IT population.

Those who hit both targets, regardless of which group they were originally assigned to, were least likely to experience the primary outcome, and those who hit neither target were most likely to experience it, they found.

Compared with patients who hit neither target, those who hit the LDL target only (adjusted HR = 0.83; 95% CI, 0.75-0.91), those who hit the CRP target only (adjusted HR = 0.89; 95% CI, 0.79-0.99) and those who hit both (adjusted HR = 0.73; 95% CI, 0.66-0.81) were at reduced risk for the primary endpoint, according to the researchers. – by Erik Swain

References:

Blazing MA, et al. Clinical Trial Update III – Pharmacology & Therapy.

Bohula May EA, et al. Abstract P6120.

Giugliano RP, et al. Abstract 68.

Giugliano RP, et al. Abstract P1131.

Giugliano RP, et al. Clinical Trial Update I – Cardiovascular Diseases: Prevention, Outcomes, Quality.

All presented at: European Society of Cardiology Congress; Aug. 29-Sept. 2, 2015; London.

Disclosures: IMPROVE-IT was funded by Merck. Blazing reports receiving a research grant and consultant fees/honoraria from Merck and receiving consultant fees/honoraria from Amgen, AstraZeneca, Novartis and Sanofi Aventis. Bohula May reports receiving consultant fees/honoraria from Merck. Giugliano reports receiving a research grant and consultant fees/honoraria from Amgen, Daiichi Sankyo and Merck and receiving consultant fees/honoraria from AngelMed, BCRI, GlaxoSmithKline, ICON, Johnson & Johnson, Lexicon, Medscape, Pfizer, Portola and St. Jude Medical.