Pitavastatin Plus Ezetimibe Better Than Either Agent Alone in Lowering LDL-C

Pitavastatin plus ezetimibe combination therapy for hypercholesterolemia is more effective than either medication as a monotherapy.

Treatment with a combination of pitavastatin plus ezetimibe is more effective than the use of either agent alone for the treatment of patients with hypercholesterolemia, according to the results of a study published in the journal Clinical Therapeutics.

A phase 3, randomized, active-controlled study (ClinicalTrials.gov identifier: NCT04643093) was conducted at 34 study sites across 3 regions in Taiwan, Australia, and New Zealand. Researchers sought to assess the efficacy of pitavastatin plus ezetimibe compared with pitavastatin 2-mg or ezetimibe 10-mg monotherapy for reducing low-density lipoprotein cholesterol (LDL-C) in patients with primary hypercholesterolemia or mixed dyslipidemia.

The study comprised a 6-week, single-blind, placebo run-in period; a 12-week double-blind treatment period; and a 2-week follow-up period. In the run-in portion, the participants were instructed to take 1 placebo capsule daily but no lipid-lowering agents. Patient eligibility was rechecked at visit 2 (baseline). Stratification was based on diagnosis of diabetes mellitus (either diabetes mellitus or non-diabetes mellitus) and baseline LDL-C level (<160 mg/dL or ≥160 mg/dL).

The primary study endpoint was the difference in the percent change in LDL-C from baseline to week 12 between the pitavastatin plus ezetimibe arm and each monotherapy arm. Secondary endpoints included percent change in other lipid profiles from baseline to each visit. All of the participants were evaluated for adverse events until the conclusion of the study.

Between September 2020 and June 2021, a total of 388 participants were randomly assigned in a 1:1:1 ratio to 1 of 3 treatment groups. Those treatment groups were the pitavastatin plus ezetimibe group (n=128), the pitavastatin 2-mg group (n=132), and the ezetimibe 10-mg group (n=128). Baseline and demographic clinical characteristics were similar among the 3 treatment arms.

…the effect on long-term safety, efficacy, and reducing the risk of CVDs by 1PC111 [pitavastatin plus ezetimibe] should be further studied in trials with longer treatment and follow-up periods.

Results of the study showed a statistically significant reduction in LDL-C level at week 12 in the pitavastatin plus ezetimibe group (-50.50% [14.9%]) compared with either the pitavastatin 2-mg group (-36.11% [11.4%]; P <.001) or the ezetimibe 10-mg group (-19.85% [12.4%]; P <.001).

Additionally, a statistically significant difference was reported between pitavastatin plus ezetimibe and each monotherapy group in terms of reduction in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Further, a trend was observed toward more efficient lowering of LDL-C levels in older patients (≥65 years of age) than among younger patients (<65 years of age) with pitavastatin plus ezetimibe therapy.

Among participants given a class I recommendation for primary prevention of atherosclerotic cardiovascular disease, the percentage of patients who achieved the LDL-C target of less than 100 mg/dL at week 12 was significantly higher in the pitavastatin plus ezetimibe group than in both monotherapy groups (P <.001). The rates of adverse events were similar across the 3 treatment groups.

Limitations of the study should be noted. Both the treatment duration and the follow-up period are relatively short. The short treatment duration might limit the ability to generalize the results of this study to the use of longer-term therapy. Moreover, the short follow-up period renders the ultimate translation of the study findings regarding cardiovascular events in clinical practice uncertain.

 “…the effect on long-term safety, efficacy, and reducing the risk of CVDs [cardiovascular diseases] by 1PC111 [pitavastatin plus ezetimibe] should be further studied in trials with longer treatment and follow-up periods,” the study authors wrote.

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.

This article originally appeared on The Cardiology Advisor


Chou M-T, McGirr A, Jong G-P, et al. Effect of 1PC111, a fixed-dose combination of pitavastatin and ezetimibe, versus pitavastatin or ezetimibe monotherapy on lipid profiles in patients with hypercholesterolemia or mixed dyslipidemia: a randomized, double-blind, multicenter, phase III study. Clin Ther. Published online August 24, 2022. doi:10.1016/j.clinthera.2022.08.006