Obicetrapib reduced LDL-C by 34.9% vs placebo in ASCVD or HeFH patients regardless of background lipid-lowering therapy type or intensity.
Does obicetrapib 10 mg once daily reduce LDL-C in patients with ASCVD or HeFH on maximally tolerated lipid lowering therapy?
Obicetrapib 10 mg daily significantly reduces LDL-C by approximately 35% in high-risk patients with ASCVD or HeFH, regardless of their background lipid-lowering therapy.
Absolute Event Rate: 0% vs 0%
Abstract Background ESC guidelines recommend more stringent LDL-C cholesterol goals for patients at highest cardiovascular risk, such as patients with prior ASCVD or heterozygous familial hypercholesterolaemia (HeFH). However, numerous studies have shown that statin monotherapy is insufficient in around 80% of patients of these patients, meaning the need for combination therapy is inevitable for most in order to achieve risk based LDL-C goals. Obicetrapib (Obi) is a novel cholesteryl ester transfer protein (CETP) inhibitor shown to reduce LDL-C in patients with ASCVD or HeFH in the Broadway and Brooklyn trials. Whether the efficacy of Obi varies by type and intensity of background lipid lowering treatment (LLT) is not known. Methods Prespecified pooled analysis of the Broadway and Brooklyn trials which randomised participants with ASCVD or HeFH and elevated LDL-C (despite maximally tolerated lipid lowering therapy LLT) to Obi 10mg once daily or placebo (Pb) with 1 year of follow up. The primary endpoint was placebo corrected change in LDL-C from baseline at 84 days with secondary endpoints of apoB and non-HDL-C change. For this analysis, patients were stratified by binary status (Yes/No) for any statin use, intensity (high, medium/low), ezetimibe, and PCSK9i as well as combination therapy (defined as any two classes of medications). Results . A total of 2778 participants were included; mean age 64 years, women (36.1%), HeFH (26.5%). Mean baseline LDL-C was 2.66 mmol/L, apoB was 93.4 mg/dL and non-HDL-C was 3.30 mmol/L. At baseline 69.3% and 21.7% were on high or moderate/low intensity statins respectively, with 9.0% on no statins. Ezetimibe use was 29.9% and use of PCSK9i 5.4%. Combination therapy was used in 28.3%, monotherapy in 68.0%, no LLT in 3.6%. The Pb-corrected reduction in LDL-C with Obi overall was 34.9% (CI 37.5,32.3) and was consistently superior to Pb across the range of background LLT (Figure Left Panel). Similar consistent benefits with Obi as compared to Pb were observed in apoB (Figure Middle Panel) and non-HDL-C (Figure Right Panel) irrespective of background LLT. Conclusion In very-high and high risk patients with ASCVD or HeFH, Obi provided significant additional reductions in LDL-C and other atherogenic lipids across the spectrum of concomitant LLTs. Obicetrapib is a promising therapy as an adjunct to existing LLT for patients whose LDL-C remains uncontrolled.Figure:Efficacy of Obicetrapib
Ray et al. (Sat,) reported a other. Obicetrapib reduced LDL-C by 34.9% vs placebo in ASCVD or HeFH patients regardless of background lipid-lowering therapy type or intensity.