Efficacy and safety of ezetimibe co-administered with atorvastatin in untreated patients with primary hypercholesterolaemia and coronary heart disease.

OBJECTIVE

Combination of ezetimibe (EZE) with a statin represents an attractive strategy for cholesterol-lowering treatment, as it inhibits the two main sources of cholesterol: absorption from the intestine (inhibited by EZE) and endogenous biosynthesis (inhibited by statins).

RESEARCH DESIGN AND METHODS

This multicentre, double-blind, placebo-controlled study randomised a total of 148 men and women with primary hypercholesterolaemia and coronary heart disease (CHD) to receive treatment for 6 weeks with either EZE 10 mg + atorvastatin 10 mg (EZE + ATV; n = 72) or placebo/atorvastatin 10 mg (ATV; n = 76). The primary efficacy variable was the mean percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to study endpoint.

RESULTS

At 6 weeks, EZE + ATV provided a significantly greater adjusted mean change from baseline in LDL-C compared with ATV monotherapy (-50.5% vs. -36.5%; p < 0.0001), equating to an additional 14.1% reduction (95% CI -17.90, -10.19) in LDL-C. A significantly higher proportion of patients on EZE + ATV achieved the new Joint British Societies (JBS 2) recommended LDL-C goal of < 2 mmol/L (62% vs. 12% with ATV alone; p < 0.0001) and the JBS 2 minimum treatment standard of < 3 mmol/L (93% vs. 79% with ATV alone). Patients receiving EZE + ATV were 12 times more likely to reach LDL-C targets (odds ratio 12.1; 95% CI 5.8, 25.1; p < 0.0001) compared with patients receiving ATV monotherapy. Clinical chemistry profiles and the incidence of adverse events were similar in both groups.

CONCLUSIONS

Adding EZE to ATV monotherapy represents an attractive and well-tolerated treatment option to bring patients at high risk of CHD to the aggressive LDL-C goals recommended by recent treatment guidelines.