# TANDEM: obicetrapib plus ezetimibe voor LDL-verlaging — Lancet fase 3

*geplaatst 2025-05-17 · Cholesterol · Lancet (London, England) · doi 10.1016/S0140-6736(25)00721-4 · https://hartvaat.nl/2025/05/17/tandem-obicetrapib-plus-ezetimibe-voor-ldl-verlaging-lancet-fase-3/*

De TANDEM-trial in de Lancet toonde dat de vaste combinatie van obicetrapib (CETP-remmer) plus ezetimibe het LDL met 55-60% verlaagde. Dit is de eerste succesvolle CETP-remmer met overtuigende LDL-verlaging en mogelijk CV-voordelen.

## English: Fixed-dose combination of obicetrapib and ezetimibe for LDL cholesterol reduction (TANDEM): a phase 3, randomised, double-blind, placebo-controlled trial.

The TANDEM trial demonstrated that a fixed-dose combination of obicetrapib (a CETP inhibitor) and ezetimibe reduced LDL cholesterol by 55-60% in statin-treated patients. This is the first positive result for a modern CETP inhibitor in combination therapy, reviving the mechanism after decades of setbacks.

## Abstract (original, from the publication)

BACKGROUND: Reducing LDL cholesterol prevents atherosclerotic cardiovascular disease (ASCVD) events. The aim of this study was to evaluate the LDL cholesterol-lowering efficacy of a fixed-dose combination (FDC) of obicetrapib, a CETP inhibitor, and ezetimibe. METHODS: This randomised, double-blind trial across 48 US sites including hospitals, private and group practices, and independent research centres included participants at least 18 years old with pre-existing or high risk for ASVCD or heterozygous familial hypercholesterolaemia with LDL cholesterol concentrations of 1·8 mmol/L (70 mg/dL) or greater despite maximally tolerated lipid-lowering therapy excluding ezetimibe, or having statin intolerance. Participants were randomly assigned (1:1:1:1) to obicetrapib 10 mg plus ezetimibe 10 mg FDC, obicetrapib 10 mg monotherapy, ezetimibe 10 mg monotherapy, or placebo administered daily for 84 days. The co-primary endpoints in the intention-to-treat population were the percent LDL cholesterol changes in the FDC group compared with placebo, ezetimibe monotherapy, and obicetrapib monotherapy, and the placebo-adjusted change in the obicetrapib monotherapy group. The trial was prospectively registered (NCT06005597) and is completed. FINDINGS: Between March 4 and July 3, 2024, 407 participants were randomly assigned. The median age was 68·0 years (IQR 62·0-73·0) and 177 (43%) were female. Mean baseline LDL cholesterol was 2·4 mmol/L, 2·5 mmol/L, 2·6 mmol/L, and 2·5 mmol/L in the placebo (n=102), ezetimibe monotherapy (n=101), obicetrapib monotherapy (n=102), and FDC groups (n=102), respectively. At day 84, percent differences in LDL cholesterol reduction with the FDC were -48·6% (95% CI -58·3 to -38·9) versus placebo, -27·9% (-37·5 to -18·4) versus ezetimibe, and -16·8% (-26·4 to -7·1) versus obicetrapib. Obicetrapib monotherapy decreased LDL cholesterol by 31·9% (22·1 to 41·6) versus placebo. Adverse event rates were similar in the FDC (52 [51%] of 102), obicetrapib (55 [54%] of 102), and ezetimibe (54 [53%] of 101) groups and lowest with placebo (38 [37%] of 102). Serious adverse event rates were generally similar across FDC (three [3%] of 102), obicetrapib (six [6%] of 102), ezetimibe (seven [7%] of 101), and placebo (four [4%] of 102) groups. Deaths occurred in one [1%] of 102 participants with FDC, one [1%] of 102 with obicetrapib, one [1%] of 101 with ezetimibe, and none with placebo. INTERPRETATION: Combination therapy of obicetrapib and ezetimibe significantly reduced LDL cholesterol. This oral, single-pill therapy could improve LDL cholesterol management in patients with pre-existing or high risk for ASCVD. FUNDING: NewAmsterdam Pharma.

Auteurs: Ashish Sarraju, Danielle Brennan, Kierstyn Hayden, Amanda Stronczek, Anne C Goldberg, Erin D Michos, Darren K McGuire, Denise Mason, Grace Tercek, Stephen J Nicholls, Douglas Kling, Annie L Neild, John Kastelein, Michael Davidson, Marc Ditmarsch, Steven E Nissen

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Bron: Lancet (London, England), https://doi.org/10.1016/S0140-6736(25)00721-4. Bijgewerkt 2026-07-03T13:30:38Z. Citeer vrij, met bronvermelding en een link naar hartvaat.nl (de url van het record). Samenvattingen zijn redactioneel werk van HartVaat; de oorspronkelijke publicaties blijven van hun uitgevers (doi). Geen medisch advies.