An investigational fixed-dose combination pill containing obicetrapib and ezetimibe may reduce low-density lipoprotein cholesterol by nearly 50% in a randomized clinical trial involving patients at high risk for cardiovascular disease.
In the study, researchers enrolled 407 adult patients with either established atherosclerotic cardiovascular disease (ASCVD), heterozygous familial hypercholesterolemia (HeFH), or multiple ASCVD risk factors. All had elevated low-density lipoprotein (LDL) cholesterol levels despite maximally tolerated lipid-lowering therapy, excluding ezetimibe, or had documented statin intolerance.
The patients were randomly assigned to receive one of four treatments daily for 84 days: the combination of obicetrapib 10 mg and ezetimibe 10 mg, obicetrapib alone, ezetimibe alone, or placebo.
On day 84, the patients in the fixed-dose combination group experienced a 48.6% greater reduction in LDL cholesterol compared with those in the placebo group. Reductions were also significantly greater compared with ezetimibe (27.9%) or obicetrapib (16.8%) monotherapy. Obicetrapib alone lowered LDL cholesterol by 31.9% vs placebo.
Mean LDL cholesterol levels decreased by 1.2 mmol/L in the combination group compared with 0.9 mmol/L for obicetrapib, 0.5 mmol/L for ezetimibe, and no statistically significant change in the placebo group.
By the end of the trial, 71% of the patients receiving the combination therapy achieved LDL cholesterol levels below 1.4 mmol/L. This target was met by 41% of the obicetrapib group, 25% of the ezetimibe group, and 7% of the placebo group.
The combination also reduced non–high-density lipoprotein cholesterol by 45.1% and apolipoprotein B by 29.2%, both important markers of cardiovascular risk. These reductions exceeded those observed with either drug alone.
Adverse events occurred at similar rates across all groups. Serious adverse events were uncommon. One death was reported in each active treatment group, with no deaths in the placebo group. The most frequent side effects were headache, fatigue, and gastrointestinal issues, with no statistically significant changes in liver enzymes, kidney function, or blood pressure.
The combination reached maximal LDL-lowering effect by day 28, which was sustained through the 84-day treatment period.
A cardiovascular outcomes trial is currently underway to assess whether the LDL reductions observed with the obicetrapib–ezetimibe combination led to fewer events such as myocardial infarction or stroke.
Disclosures are reported in the published study.
Source: The Lancet
